Academic literature on the topic 'In vitro release kinetic models'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'In vitro release kinetic models.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "In vitro release kinetic models"
1
Costa, André Lima de Oliveira, Paula Cristina Rezende Enéas, Tiago Assis Miranda, Sueli Aparecida Mingoti, Cristina Duarte Vianna Soares, and Gerson Antônio Pianetti. "In vitro dissolution kinetic for mycophenolic acid derivatives tablets." Brazilian Journal of Pharmaceutical Sciences 49, no. 2 (June 2013): 311–19. http://dx.doi.org/10.1590/s1984-82502013000200013.
Full textAbstract:
Mycophenolate mofetil (MMF) and mycophenolate sodium (MPS) are an ester and a salt of mycophenolic acid. They have different kinetic in vivo characteristics due to differences in molecular structures, physicochemical properties and formulations administered. In this study, dissolution profiles of reference products were tested in different media to evaluate the effect of pH, kinetic dissolution and the best statistical model that can be used to predict the release of both drugs. The drug release was determined by using a validated ultraviolet spectrophotometry method, λ 250 nm. The method showed to be selective, linear, precise and accurate for MMF in 0.1 M HCl and MPS in sodium phosphate buffer pH 6.8. Dissolution kinetics models of zero order, first order, Higuchi, Hixson-Crowell and Weibull were applied to data in order to select the best fit by linear regression. The regression parameters were estimated and the models were evaluated with the results of residuals and coefficient of determination. The residuals obtained from dissolution kinetics models were random, uncorrelated, and normally distributed with constant variance. The R² values (74.7% for MMF and 95.8% for MPS) demonstrated good ability of the Weibull regression to explain the variability and to predict the drugs' release.
2
Quintal Martínez, Juan Pablo, Jorge Carlos Ruiz Ruiz, and Maira Rubí Segura Campos. "Release Kinetic Studies of Stevia rebaudiana Extract Capsules from Sodium Alginate and Inulin by Ionotropic Gelation." Advances in Materials Science and Engineering 2018 (July 11, 2018): 1–8. http://dx.doi.org/10.1155/2018/6354924.
Full textAbstract:
This study was oriented towards encapsulation of S. rebaudiana extract and the study of its release kinetics. The desired encapsulation was achieved by the ionotropic gelation method using sodium alginate and inulin of polymeric constituents. Characterization of the capsules was performed by micrometric properties, encapsulation efficiency, in vitro extract release analysis, and biological activity of released extract. The in vitro release profiles from different capsules were applied on different kinetic models. The prepared capsules were found spherical in shape with diameters ranging from 2.07 to 2.63 mm, having the encapsulation efficiencies of 43.77% and 56.53% for phenolic compounds and steviol glycosides, respectively. The best-fit model with the highest correlation coefficient was observed in the Ritger–Peppas model, indicating diffusion controlled principle. The release exponent n value obtained from the Korsmeyer–Peppas model varied between 0.2273 and 1.1719, confirming that the mechanism of S. rebaudiana extract bioactive compounds release was diffusion controlled.
3
Kumar, B., and G. Jeyabalan. "Development of Anti-diabetic Niosomes Formulation Containing Metformin and Gliclazide." Indian Journal of Pharmaceutical and Biological Research 5, no. 02 (June 30, 2017): 24–28. http://dx.doi.org/10.30750/ijpbr.5.2.5.
Full textAbstract:
Metformin/Gliclazide niosomes were formulated with span 60 by ether injection method. Three batches MG1-MG3 were prepared in order to study influence of drug polymer ratio on the niosomes formation and in vitro drug release. The formulated niosomes were characterized by drug entrapment, vesicle size determination, and in vitro drug release. Optimized concentration of span 60 and cholesterol was found to be 1:1. In the in-vitro study, niosomes formulation of MG1 showed high percentage of drug release, 40.18 to 45.75% for about 8 hrs. This indicated that this batch of niosomes formulation exhibit sustained drug release pattern as the niosomes act as reservoir system for continuous delivery of drug. The quantity of Metformin/Gliclazide present in the niosomes and the release medium were estimated by a validated HPLC method. The formulated niosomes had acceptable physicochemical characters and released the drug over 6-8 h. The data obtained from in vitro release studies were fitted with various kinetic models and was found to follow Higuchi kinetics.
4
Dewan, Irin, Md Maynul Islam, Maksud Al-Hasan, Joydeb Nath, Sefat Sultana, and Md Sohel Rana. "Surface Deposition and Coalescence and Coacervation Phase Separation Methods: In Vitro Study and Compatibility Analysis of Eudragit RS30D, Eudragit RL30D, and Carbopol-PLA Loaded Metronidazole Microspheres." Journal of Pharmaceutics 2015 (November 16, 2015): 1–10. http://dx.doi.org/10.1155/2015/254930.
Full textAbstract:
Metronidazole (MTZ) has extremely broad spectrum of protozoal and antimicrobial activity and is clinically effective in trichomoniasis, amoebic colitis, and giardiasis. This study was performed to formulate and evaluate the MTZ loaded microspheres by coacervation phase separation and surface deposition and coalescence methods using different polymers like Gelatin, Carbopol 934P, Polylactic Acid (PLA), Eudragit RS30D, and Eudragit RL30D to acquire sustained release of drug. In vitro dissolution studies were carried out in phosphate buffer (pH 7.4) for 8 hours according to USP paddle method. The maximum and minimum release of MTZ from microspheres observed were 84.81% and 76.6% for coacervation and 95.07% and 80.07% for surface deposition method, respectively, after 8 hours. Release kinetics was studied in different mathematical release models. The SEM and FTIR studies confirm good spheres and smooth surface as well as interaction between drug and polymers. Though release kinetic is uncertain, the best fit was obtained with the Korsmeyer kinetic model with release exponent (n) lying between 0.45 and 0.89. In vitro studies showed that MTZ microspheres with different polymers might be a good candidate as sustained drug delivery system to treat bacterial infections.
5
Hurtado, M. González, J. Rieumont Briones, Laura M. Castro González, E. Ortiz Islas, and Inti Zumeta Dube. "Kinetic studies of the release profiles of antiepileptic drug released from a nanostructured TiO2 matrix." JOURNAL OF ADVANCES IN CHEMISTRY 12, no. 4 (December 16, 2016): 4365–73. http://dx.doi.org/10.24297/jac.v12i4.2176.
Full textAbstract:
In this paper is reported the “in vitro” release kinetic studies of antiepileptic drugs released from an inorganic, titanium oxide (TiO2) porous matrix. In order to determine the drug release mechanism, the experimental values were fitted to different mathematical models: zero-order, firs-order, Higuchi, Hixson-Crowel and Peppas. TiO2 was prepared by the sol-gel method adding valproic acid (VPA) or phenytoine (DHP) during the titanium n-butoxide hydrolysis step. The drug-TiO2 systems were observed by scanning electron microscopy. The “in vitro” release experiments were performed at laboratory scale following the United States Pharmacopeia (USP) standards. The obtained materials have a morphology of nanoparticle agglomerates. The particles have different sizes with some roughness and spherical shape. Peppas model suggests for both systems, that the release mechanism is controlled by two parallel processes. The first one is by diffusion of the drug through the matrix and the second is related to a gradient of constant diffusion by ingress of the solvent in the matrix.
6
Iovanov, Rareș Iuliu, Ioan Tomuță, and Sorin Emilian Leucuța. "Development of a reservoir type prolonged release system with felodipine via simplex methodology." Medicine and Pharmacy Reports 89, no. 1 (September 28, 2015): 128–36. http://dx.doi.org/10.15386/cjmed-526.
Full textAbstract:
Background and aims. Felodipine is a dihydropyridine calcium antagonist that presents good characteristics to be formulated as prolonged release preparations. The aim of the study was the formulation and in vitro characterization of a reservoir type prolonged release system with felodipine, over a 12 hours period using the Simplex method.Methods. The first step of the Simplex method was to study the influence of the granules coating method on the felodipine release. Furthermore the influence of the coating polymer type, the percent of the coating polymer and the percent of pore forming agent in the coating on the felodipine release were studied. Afterwards these two steps of the experimental design the percent of Surelease applied on the felodipine loaded granules and the percent of pore former in the polymeric coating formulation variables were studied. The in vitro dissolution of model drug was performed in phosphate buffer solution (pH 6.5) with 1% sodium lauryl sulfate. The released drug quantification was done using an HPLC method. The release kinetics of felodipine from the final granules was assessed using different mathematical models.Results. A 12 hours release was achieved using granules with the size between 315 – 500 µm coated with 45% Surelease with different pore former ratios in the coating via the top-spray method.Conclusion. We have prepared prolonged release coated granules with felodipine using a fluid bed system based on the Simplex method. The API from the studied final formulations was released over a 12 hours period and the release kinetics of the model drug substance from the optimized preparations fitted best the Higuchi and Peppas kinetic models.
7
Gönüllü, Ü., P. Gürpınar, and M. Üner. "Double-layer Tablets of Lornoxicam: Validation of Quantification Method, In vitro Dissolution and Kinetic Modelling." Tropical Journal of Pharmaceutical Research 14, no. 9 (October 12, 2015): 1659–66. http://dx.doi.org/10.4314/tjpr.v14i9.16.
Full textAbstract:
Purpose: To formulate double-layer tablets of lornoxicam (LRX) prepared by direct compression method and evaluate their physical and drug release characteristics.Methods: The outer layer of tablets, composed of microcrystalline cellulose (MCC), starch and lactose, incorporated tan initial or prompt dose of the drug (4 mg) for immediate release. Hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP K90) and carbomer, in varying concentrations, were used to prepare the tablet cores for sustained drug delivery. Weight variation, dimensions, hardness, tensile strength, friability and disintegration time of the tablets were evaluated. Drug release from double-layer tablets as well as kinetic models of drug release were determined after validating the method used for the quantification of the drug. The analytical method for quantification of LRX by UV spectroscopy was validated and verified for linearity, intra-day and inter-day precision, accuracy, recovery and specifity.Results: Tablet cores based on HPMC and HPMC:PVP K90 mixture displayed better compression and flow properties (good and fair to passable) than those formulated with PVP K90 and carbomer (poor). Satisfactory results were obtained from all the tablet formulations met compendial requirements. The slowest drug release rate was obtained with tablet cores based on PVP K90 (1.21 mg%.h-1). Drug release followed Higuchi kinetic model and the tablet cores released drug by diffusion/polymer relaxation or diffusion/erosion.Conclusion: Double-layer tablet formulation of lornoxicam based on HPMC or HPMC-PVP mixture is suitable for the treatment of inflammatory and painful conditions.Keywords: Lornoxicam, Controlled release, Double-layer tablets, Non-steroidal antiinflammatory drug, Oral delivery
8
Haroun, Ahmed, Ali Osman, Sayed Ahmed, and Ahmed H. Elghandour. "Synthesis and Characterization of Ibuprofen Delivery System Based on β-cyclodextrin/Itaconic Acid Copolymer." Trends in Sciences 19, no. 19 (August 31, 2022): 5825. http://dx.doi.org/10.48048/tis.2022.5825.
Full textAbstract:
This study aims at preparation and characterization of drug delivery system based on grafted beta-cyclodextrin (β-CD) with itaconic acid (IA) using free-radical copolymerization technique, in the presence of N, N'-methylene bisacrylamide (BIS) and ammonium persulphate (APS) as a crosslinker and an initiator, respectively. The obtained copolymer (CD-PIA) was characterized using Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), X-ray diffraction patterns (XRD), transmission and scanning electron microscopes (TEM and SEM). Ibuprofen (IBU), as an anti-inflammatory drug model, was loaded during the preparation. The kinetic of the copolymerization was investigated in terms of grafting yield (GY %), grafting efficiency (GE %) and monomer conversion (%). Moreover, in vitro IBU release and kinetic of released using the different mathematical models (0-order, first-order and Higushi) were carried out in simulated gastric and intestinal fluids (SGF and SIF at pH 1.2 and 7.4, respectively) at 37 °. The results proved the successful preparation of the target copolymer with irregular spherical-like shape and particle size around 14 - 27.7 nm. After IBU loading, the copolymer exhibited thermal stability with crystalline nature. Also, the study showed that the synthesized copolymer, especially which high IA content is controlled the release of IBU after 4 h. Besides, it could be used as a potential IBU delivery system with sustained-release followed the first-order kinetic over 24 h.
HIGHLIGHTS
The nanogels drug carriers used for nonsteroidal anti-inflammatory drugs to overcome the unfavorable release in the stomach due to unforeseen pH alterations
The polymeric grafted β-CD derivatives using IA represent a unique class of the host materials with tunable inclusion properties and high affinity for Ibuprofen release
In vitro kinetic of IBU released showed the best fit with first-order model
GRAPHICAL ABSTRACT
9
Khalid, Ikrima, Mahmood Ahmad, Muhammad Usman Minhas, and Muhammad Sohail. "Formulation and in vitro evaluation of mucoadhesive controlled release matrix tablets of flurbiprofen using response surface methodology." Brazilian Journal of Pharmaceutical Sciences 50, no. 3 (September 2014): 493–504. http://dx.doi.org/10.1590/s1984-82502014000300007.
Full textAbstract:
The objective of the current study was to formulate mucoadhesive controlled release matrix tablets of flurbiprofen and to optimize its drug release profile and bioadhesion using response surface methodology. Tablets were prepared via a direct compression technique and evaluated for in vitro dissolution parameters and bioadhesive strength. A central composite design for two factors at five levels each was employed for the study. Carbopol 934 and sodium carboxymethylcellulose were taken as independent variables. Fourier transform infrared (FTIR) spectroscopy studies were performed to observe the stability of the drug during direct compression and to check for a drug-polymer interaction. Various kinetic models were applied to evaluate drug release from the polymers. Contour and response surface plots were also drawn to portray the relationship between the independent and response variables. Mucoadhesive tablets of flurbiprofen exhibited non-Fickian drug release kinetics extending towards zero-order, with some formulations (F3, F8, and F9) reaching super case II transport, as the value of the release rate exponent (n) varied between 0.584 and 1.104. Polynomial mathematical models, generated for various response variables, were found to be statistically significant (P<0.05). The study also helped to find the drug's optimum formulation with excellent bioadhesive strength. Suitable combinations of two polymers provided adequate release profile, while carbopol 934 produced more bioadhesion.
10
Narissara Kulpreechanan and Feuangthit Niyamissara Sorasitthiyanukarn. "Evaluation of in vitro release kinetics of Capsaicin-loaded chitosan nanoparticles using DDSolver." International Journal of Research in Pharmaceutical Sciences 11, no. 3 (July 31, 2020): 4555–59. http://dx.doi.org/10.26452/ijrps.v11i3.2685.
Full textAbstract:
The present aim is to evaluate the release profile and its release kinetics of encapsulated capsaicin from chitosan nanoparticles using the software DDSolver. The release study was performed by using a dialysis technique in PBS solutions with different pHs (1.2, 6.8 and 7.4) to mimics the different gastrointestinal tract and circulatory system pH ranges as a releasing medium. The nanoparticles were prepared using o/w emulsification and ionotropic gelation technique under optimal condition obtained from response surface methodology (RSM) design as described in our previous study. These nanoparticles were around 180 nm in average hydrodynamic size and encapsulation efficiency percentage around 70%, respectively. In vitro drug release study suggested that the chitosan nanoparticles can potentially use to controlled and sustained release of capsaicin over at least 96. The kinetic release analysis results by DDSolver software indicated that Weibull model was suggested to be the best dynamic models with highest R2adjusted and model selection criteria (MSC) and lowest Akaike information criterion (AIC), respectively, for capsaicin loaded chitosan nanoparticles. The release mechanism of capsaicin from nanoparticles was found to be Fickian diffusion. The results suggest that the chitosan nanoparticles can be applied for the controlled and sustained release of capsaicin in the gastrointestinal tract and circulatory system.
Dissertations / Theses on the topic "In vitro release kinetic models"
1
KOCERGINSKY, Patrícia de Oliveira. "Criptococose e determinação do efeito antifúngico in vitro e in vivo por sistema de liberação controlada com ciclopirox olamina." Universidade Federal de Pernambuco, 2013. https://repositorio.ufpe.br/handle/123456789/18294.
Full textAbstract:
Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-02-13T13:18:57Z
No. of bitstreams: 2
license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5)
TESE colação de grau.pdf: 1971286 bytes, checksum: 680d0e24d2f0efbe0313ab8752f1cc93 (MD5)Made available in DSpace on 2017-02-13T13:18:57Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) TESE colação de grau.pdf: 1971286 bytes, checksum: 680d0e24d2f0efbe0313ab8752f1cc93 (MD5) Previous issue date: 2013-02-22
CNPq
A criptococose é uma infecção fúngica predominantemente oportunista cujos principais agentes etiológicos são Cryptococcus neoformans e C. gattii. O tratamento de escolha para a micose é a anfotericina B associada ou não a 5-fluorocitosina seguido de terapia de manutenção com fluconazol. Contudo, falhas no tratamento associadas à toxicidade e ao aparecimento de resistência aos fármacos têm sido relatadas, o que torna essencial a descoberta de novas alternativas terapêuticas, como a ciclopirox olamina (CPO). Neste contexto, o objetivo deste estudo foi caracterizar e avaliar a ação in vitro e in vivo da CPO livre e encapsulada em lipossomas frente a amostras de Cryptococcus neoformans para futura aplicação no tratamento da criptococose sistêmica. Foram obtidas 30 amostras de Cryptococcus neoformans provenientes de pacientes imunocomprometidos. A preparação dos lipossomas convencionais e furtivos de CPO foi realizada pelo método da hidratação do filme lipídico e a caracterização foi realizada avaliando os seguintes parâmetros: tamanho de partícula, Índice de Polidispersão (PDI) e taxa de encapsulação (EE%). Para otimização dos constituintes lipídicos, foi realizado um planejamento fatorial fracionado a 24-1 a partir da melhor formulação obtida nos estudos de pré-formulação. A cinética de liberação in vitro foi conduzida para avaliar e comparar estatisticamente o perfil de liberação dos sistemas convencional e furtivo. Adicionalmente, testes de susceptibilidade antifúngica foram realizados de acordo com Clinical and Laboratotry Standards Institute (CLSI). Para caracterização molecular dos isolados, PCR fingerprinting foi conduzida utilizando os primers M13 e URA5. O estudo in vivo foi conduzido com camundongos imunossuprimidos, infectados com Cryptococcus neoformans (106 cels/mL) e tratados com CPO lipossomal (Lipo-CPO) (0.5 mg/Kg). As concentrações de CPO utilizadas na forma livre e encapsuladas em lipossomas convencionais e furtivos variaram de 0,30 a 625 µg/mL. Os resultados do planejamento fatorial mostraram que o ponto central apresentou características proeminentes com redução do tamanho de partícula em 17,1%; melhora do PDI em 15,34% e da quantidade de fármaco encapsulado (25%). A cinética do lipossoma furtivo apresentou uma velocidade de liberação mais controlada quando comparada ao lipossoma convencional. Com relação ao teste de susceptibilidade, todos os inóculos foram susceptíveis a CPO livre, com atividade fungistática entre 0,30 e 0,61 g/mL e fungicida entre 1,22 e 4,88 g/mL. Não houve diferença relacionada à atividade antifúngica entre as formulações lipossomais convencionais e furtivas. A atividade fungistática dos lipossomas foi observada em concentrações variando de 1,22 e 2,44 g/mL. A faixa das concentrações fungicidas foi de 1,22 a 9,76 g/mL. O padrão de bandas do URA5 revelou que todos os isolados apresentam genótipo VNI, característico de C. neoformans. Lipo-CPO apresentou eficácia antifúngica comparada à anfotericina B após 14 dias de infecção, reduzindo a carga fúngica em aproximadamente 8% no baço, 41% no fígado, 63% no pulmão e 89% no cérebro. O exame histológico evidenciou infiltrado celular no fígado dos grupos tratados com Lipo-CPO e anfotericina B, porém com menor intensidade quando comparado ao grupo controle. O estudo sugere que a CPO encapsulada em lipossomas apresenta significativa ação antimicótica frente às amostras sistêmicas de C. neoformans, reforçando seu potencial na terapêutica da criptococose.
Cryptococcosis is an opportunistic fungal infection whose the main ethiological agents are Cryptococcus neoformans and C. gattii. The treatment of choice for this mycosis is amphotericin B combined or not with 5-fluorocytosine, followed by maintenance therapy with fluconazole. However treatment failures associated with toxicity and drug resistance has been reported, which makes it essential to the discovery of new therapies, such as ciclopirox olamine (CPO). The purpose of this study was to characterize and evaluate the in vitro and in vivo antifungal activity of ciclopirox olamine in its free form and encapsulated in liposomes against thirty Cryptococcus neoformans isolates obtained from immunocompromised patients for future application in systemic cryptococcosis treatment. Preparation of conventional and stealth liposomes was performed to define particle size, polydispersity index (PDI), CPO amount of encapsulated and efficiency of encapsulation (EE%). For optimization of liposomal lipid constituents, a 24-1 fractional factorial design was carried out from the prominent formulation obtained in pre-characterization studies. In vitro release kinetics was conducted to evaluate and compare statistically the release profile of conventional and stealth liposomes. Antifungal susceptibility testing was conducted in accordance with the reference method. Regarding molecular characterization, PCR fingerprinting was carried out by using MT3 and URA5 primers. Concentrations of CPO used in free form and encapsulated into stealth and conventional liposomes ranged from 625 to 0.3 g.mL-1. Despite of the central point of the factorial design have increased the total lipids amount in 35.52%, it showed prominent characteristics when compared with the L4 formulation with improvement of the mean size in 17.1%, PDI in 15.34% and CPO amount in 25%. The minimum concentrations of stearylamine to obtain the stable formulation for one month was 5.88 mM. . Kinetics of stealth liposomes showed a release profile more controlled as compared to conventional liposomes. All inoculations were susceptible to CPO in its free form, presenting fungistatic activity between 0.3 and 0.61 g.mL-1 and fungicidal activity between 1.22 and 4.88 g.mL-1. There was no difference with respect to antimycotic activity between conventional and stealth liposomal formulations. Fungistatic activity of liposomes was observed at concentrations ranging from 1.22 and 2.44 g.mL-1. Fungicidal concentration range was 1.22-9.76 g.mL-1. The URA5 profile analized demonstrated all isolates are VNI genotype (C. neoformans). The treatment with Lipo-CPO showed a reduction of 8% of the C. neoformans population in spleen, 40.8% in liver, 63% in lungs and 89% in brain after 14 days of infection. Histological examination revealed cell infiltrate either Lipo-CPO or Amphotericin B treated groups, but less intense when compared to control group. The results suggest that Ciclopirox olamine loaded-liposomes have significant antimycotic activity against Cryptoccocus spp, reinforcing its potential for in vivo studies and its application in cryptococcosis treatment.
2
Syarifuddin, Adiansyah. "Multi sensory integration as a strategy to compensate for sodium and fat reduction in food." Thesis, Dijon, 2015. http://www.theses.fr/2015DIJOS088.
Full textAbstract:
Au cours des dernières années, les autorités sanitaires ont recommandé une réduction de la teneur en sel et en gras dans la consommation alimentaire quotidienne. Cependant, les aliments à teneur réduite en sel et en gras sont souvent peu appréciés par les consommateurs, ce qui a amené au développement des recherches sur les stratégies possibles pour maintenir l’acceptabilité des aliments tout en réduisant les teneurs en ces ingrédients. Dans cette thèse, l’intégration multi-sensorielle et les cinétiques de libération du sel et des arômes mesurées in vitro ont été étudiés pour évaluer leur potentialité à compenser une réduction en sel et matière grasse d’un fromage modèle de composition variable et d’un fromage réel (type trappiste).Dans une première étape, une approche sensorielle a permis d’étudier les interactions multi-sensorielles arômes-saveurs-texture pour les formages modèles et réels. La structure et la perception sensorielle de vingt-quatre modèles fromagers variant en composition (2 niveaux de gras, 2 de sel, 2 de pH à l’emprésurage) et aromatisés avec un arôme de sardine (associé au sel), d'un arôme de beurre (associé au gras) ou non aromatisés (témoin) ont été caractérisés par des mesures rhéologiques (compression uniaxiale) et des mesures sensorielles (profil descriptif). Les résultats ont montré une influence de la composition sur la structure et la texture perçue des produits. Par ailleurs, l’arôme sardine a conduit à une perception plus salé ; l’arôme de beurre a permis de renforcer la perception du caractère gras. Toutefois cette influence des arômes sur les autres dimensions sensorielles est fonction de la texture des produits donc de leur composition et de leur structure. Ces résultats ont été étendus à des fromages réels avec toutefois des spécificités. Si l’arôme sardine renforce la perception du sel, seul l’arôme de beurre associé à l’arôme de sardine permet de renforcer le caractère gras.Dans une deuxième étape, une approche physico-chimique a été développée pour explorer les cinétiques de libération des stimuli odorants et sapides dans des conditions simulant la mastication in vitro à l’aide d’un simulateur de mastication. L’objectif était d’utiliser les données ainsi obtenues pour expliquer l’influence de la structure des produits et de leur déstructuration lors de la mastication sur les effets sensoriels observés dans la première étape. Les modèles fromagers et les fromages réels ont été ainsi étudiés. La libération des composés volatils a été évaluée en connectant le simulateur de mastication à un spectromètre de masse à pression atmosphérique (PTR-MS) ; la libération du sodium a été suivie grâce à une sonde de conductivité. Les résultats ont montré une influence des trois paramètres de composition (teneur en matière grasse, en sel et pH à l’emprésurage) sur les cinétiques de la libération des arômes. Cette variation dépend néanmoins de la nature de l’arôme suivi ; les arômes plus hydrophobes étant moins sensibles aux variations de la teneur en matière grasse et plus sensibles aux variations de pH et donc à la structure du produit. La cinétique de libération du sel lors de la mastication in vitro est aussi largement influencée par la composition et la structure des produits. Outre la teneur en sel qui conditionne les quantités libérées, la teneur en matière grasse et le pH à l’emprésurage module la cinétique de libération du sel. Au final, ces travaux montrent une importante contribution de la cinétique de libération et donc probablement de la temporalité des sensations dans perception globale du sel et de la matière grasse lors de la consommation d’un aliment complexeIn recent years, health authorities worldwide advise for a reduction of salt and fat in daily food consumption. However, foods with reduced salt and fat content are often not appreciated by consumers, Therefore, the formulation of low-salt-fat foods that maintain acceptability is a major concern in food research. In this thesis, the multi-sensory integration and release kinetics of flavor compounds were explored as strategies to compensate for salt and fat reduction in cheese products (model cheeses and real cheeses). The objective was to better understand the mechanisms leading to aroma and salt release during mastication and to evaluate how the matrix composition and structure influence salt and aroma release profile.Multisensory integration approach to compensate for salt and fat reduction was studied in a first step. The structure and sensory perception of 24 cheese models varying in composition (2 levels of fat, 2 salt, 2 pH at renneting) and flavored with either a sardine aroma (associated to salt), a butter aroma (associated to fat) or not flavoured (control) were characterised by rheological measurements (uniaxial compression) and sensory evaluation (descriptive analysis). The results demonstrated an influence of the composition on the products structure and perceived texture. Furthermore, a significant saltiness enhancement was induced by sardine aroma while significant fat perception enhancement was induced by butter aroma. However, this influence of the aroma on other sensory dimensions depends on the texture of the products thus on their composition and structure. These results have been extended to real cheeses but with specificities. If the sardine flavor enhanced the perception of salt, only butter-sardine-flavor enhanced the perception of fat.In a second step, a physico-chemical approach was developed to explore the release kinetic of flavor compounds during in vitro breakdown using a chewing simulator. The aim was to use these data to explain the influence of the structure of model cheeses and real cheeses and their breakdown during chewing on sensory effects observed in the first step. Volatile compounds release was monitored by connecting the chewing simulator to a proton transfer reaction-mass spectrometry (PTR-MS), while salt release was monitored using a conductivity probe. Results showed that product composition and structure (fat, salt and pH at renneting) influenced aroma release, which however depends on the nature of the aroma: the more hydrophobic compounds are less sensitive to variations in fat content and more sensitive to variations in pH and therefore to the products structure. The salt release kinetic during in vitro chewing was also influenced by the composition and structure of the products. Indeed, beyond salt content which determined the amount of salt released, fat content and the pH at renneting modulated the release kinetic. In conclusion, this work showed a significant impact of the flavor compounds release kinetic and probably of temporality of sensations on the overall perception of salt and fat when consuming a complex food
3
Marcheix, Pierre-Sylvain. "Evaluation in vitro et in vivo d’un polymère biorésorbable à la Gentamycine dans le traitement expérimental d’infections ostéo-articulaires." Thesis, Limoges, 2016. http://www.theses.fr/2016LIMO0079/document.
Full textAbstract:
Le traitement d'une infection ostéo-articulaire nécessite une prise en charge longue, obligeant à des chirurgies itératives et à un traitement antibiotique systémique prolongé. À ce jour, le polyméthacrylate de méthyle est le vecteur d’antibiotique local le plus fréquemment utilisé chez l’homme pour traiter une infection ostéo-articulaire. Cependant les PMMA sont non résorbables et obligent à multiplier les interventions chirurgicales afin d’aboutir au traitement définitif de l’infection ostéo-articulaire. Le PMMA ne permet pas une libération complète de l’antibiotique avec de surcroît des doses inférieures à la CMI du germe en cause, pouvant faciliter l’émergence de bactéries résistantes. L'objectif de notre travail était d’obtenir une libération locale efficace et prolongée d’antibiotique grâce à un polymère entièrement résorbable. Le cahier des charges établi pour l’élaboration de ce polymère était le suivant : système matriciel offrant une libération de gentamicine à une dose de 1 à 2 mg/jour/g de mélange sur une période de plus de 10 jours. De plus, le polymère devait être bio-résorbable, c’est-à-dire qu’il devait pouvoir être dégradé jusqu'à obtenir des fragments pouvant être éliminés naturellement par l'organisme. Afin de répondre à ces exigences, il a été créé le PLA50P, Poly(D,L-acide lactique) de haut poids moléculaire. Afin d’obtenir le mélange gentamycine-PLA, une technique de compression des poudres des deux composants a été mise en œuvre. Ce polymère pouvait être stérilisé par -irradiation, sans influence sur les caractéristiques de relargage du polymère.La cinétique in vitro de la gentamicine relarguée par le PLA50GS montrait un pic maximum de gentamicine libérée obtenu à 12 jours et une stabilisation ensuite jusqu’à 63 jours de la quantité relarguée. La quantité cumulée de gentamicine relarguée à 3 semaines in vitro est de 54 % de la quantité contenue initialement dans PLA50GS. In vivo, nous observions une libération in situ de 5,1 µg/mL de gentamicine à J3, de 1,9 µg/mL de gentamicine à J7 et de 0 µg/mL à 5 semaines avec disparition de PLA50GS à l’examen macroscopique. Nous avons ainsi pu mettre en évidence, in vitro et in vivo, un relargage de la gentamicine à des doses supérieures à la CMI du germe et ce pendant plus de trois semaines.Afin de confirmer ces observations, nous avons ensuite mis au point un modèle d’infection périostée chez le rat. Pour ce faire nous avons utilisé des rats âgés de 10 à 12 semaines avec une injection au contact de l’os et au 1/3 moyen de la patte arrière de deux fois 100 ml de SAMS d’origine animale. L’utilisation du PLA50GS a montré sa supériorité par rapport à une administration parentérale d’une dose équivalente de Gentamicine avec une négativation du contage bactériologique chez tous les rats traités par le polymère chargé à la Gentamicine. Nous avons ensuite voulu traiter une infection articulaire grâce à notre polymère. Nous avons donc créé un modèle animal utilisant un lapin femelle de 4 kg avec une injection de 1 ml d’une solution à 103 CFU/ml de staphylococcus méthi-sensible d’origine léporidée. Le PLA50GS nous a permis de réduire très significativement la charge bactérienne intra-articulaire (baisse de 3 à 4 log10 soit 1000 à 10000 fois moins de bactéries) alors que le traitement antibiotique par voie générale dit de référence ne nous a pas permis de réduire l’infection intra-articulaire de façon significative par rapport au groupe non traité. Le PLA50GS nous a ainsi permis de réduire l’infection de 3 log10 par rapport aux autres groupes avec 2 lapins sur 6 guéris de leur infection.Le PLA50GS présente, ainsi, les caractéristiques suivantes : (i) stabilité de la Gentamicine au sein du polymère, (ii) polymère sous forme de poudre stable, (iii) relargage prolongé de la Gentamicine pendant plusieurs semaines, (iv) effet « burst » présent mais limité, (v) très bonne biotolérance, et (vi) efficacité supérieure aux traitements antimicrobiens classiquesThe treatment of soft-tissue infections, osteomyelitis, and acute or chronic septic arthritis is a lengthy process that involves repeated surgical procedures and the systemic administration of antibiotics for at least 6 weeks to 3 months. Poor diffusion of antibiotics into bones and joints requires high doses given parenterally for long periods. At present, the antibiotic vector most widely used in humans with bone or joint infections is polymethylmethacrylate. Because PMMA is not bioabsorbable, multiple surgical procedures are required to eradicate infection. Furthermore, PMMA does not release its full antibiotic load over time and may yield local antibiotic concentrations lower than the minimal inhibitory concentration of the causative organism, thereby promoting the emergence of resistant strains. The objective of our work was to develop a fully bioabsorbable polymer capable of ensuring the prolonged and efficient release of its antibiotic load, thus improving the management of bone and joint infections. The specifications for the polymer included the release by the matrix system of 1-2 mg of gentamicin per day and per gram of mixture over more than 10 days. Other specifications were appropriate physical characteristics, a drug release rate sufficient to ensure optimal treatment safety, and ease of implantation. The polymer was also to be bioabsorbable, i.e., subject to degradation into fragments capable of being eliminated naturally by the body. High-molecular weight PLA50P, Poly(D,L-lactic acid) was created and found to meet these specifications. Use of this polymer as large particles (0.5 to 1 mm) limited the initial burst phenomenon. A gentamicin-PLA50P mixture was obtained by compression of the two components prepared in powder form. The antibiotic load was set at 20% to limit the initial burst. The polymer can be sterilized by gamma irradiation, which has no effect on drug release characteristics.In vitro kinetic studies of gentamicin release by the polymer showed a peak on day 12 followed by a plateau that lasted until day 63. After 3 weeks, the cumulative amount of gentamicin released in vitro was 54% of the total amount loaded onto the polymer. In vivo gentamicin concentrations measured in situ were 5.1 µg/mL on day 3, 1.9 µg/mL on day 7, and 0 µg/mL on day 35, when the polymer was no longer visible to the naked eye. Thus, both in vivo and in vitro, gentamicin was released in concentrations greater than the MIC of the microorganism, for longer than 3 weeks.To test the gentamicin-loaded polymer, we created a rat model of periosteal infection. Rats aged 10-12 weeks received two 100 mL injections of methicillin-susceptible Staphylococcus aureus collected from animals, into the middle third of the hind leg, in contact with the bone. Treatment with gentamicin-loaded PLA50P proved superior over parenteral administration of an equivalent gentamicin dose, consistently reverting the bacteriological cultures to negative. We then created a rabbit model of septic arthritis. A doe weighing 4 kg received an add intraarticular injection of 1 mL of a solution containing 103 cfu/mL of a methicillin-sensitive S. aureus strain collected from another rabbit. Gentamicin-loaded PLA50P treatment induced a highly significant drop in the intraarticular bacterial load (by 3-4 log10), whereas standard systemic gentamicin therapy failed to significantly diminish bacterial counts comparatively to the untreated controls. Thus, gentamicin-loaded PLA50P diminished the bacterial load by 3 log10 comparatively to the other groups and allowed eradication of the infection in 2 of the 6 rabbits.In sum, gentamicin-loaded PLA50P (i) ensures the stability of the antibiotic; (ii) is available as a stable powder; (iii) ensures the prolonged release of gentamicin over several weeks; (iv) produces a limited burst effect; (v) exhibits very good biotolerance; (vi) and is more effective than standard antimicrobial therapy
4
Stolberg-Stolberg, Josef Verfasser], Rainer H. H. [Akademischer Betreuer] Burgkart, Andreas K. [Akademischer Betreuer] Nüssler, and Andreas B. [Akademischer Betreuer] [Imhoff. "Effects of Cartilage Impact with and without Fracture on Chondrocyte Viability and the Release of Inflammatory Markers in Two In vitro Models / Josef Stolberg-Stolberg. Gutachter: Andreas K. Nüssler ; Andreas Imhoff ; Rainer H. H. Burgkart. Betreuer: Rainer H. H. Burgkart." München : Universitätsbibliothek der TU München, 2014. http://d-nb.info/1064976158/34.
Full text
5
Billanou, Ian. "Modélisation expérimentale et théorique pour la quantification du débit sanguin par Tomographie à Emission de Positrons." Thesis, Toulouse, INPT, 2010. http://www.theses.fr/2010INPT0006/document.
Full textAbstract:
La Tomographie à Emission de Positrons (TEP) permet d'obtenir une mesure dynamique et résolue en espace de la concentration d'un traceur radioactif injecté au patient. La quantification du débit sanguin cérébral par TEP repose sur l'utilisation d'un modèle cinétique le reliant à la variation spatio-temporelle de la concentration du traceur dans le cerveau. Différents modèles cinétiques sont proposés dans la littérature. Cependant, la majorité d'entre eux repose sur une modélisation compartimentale de l'organe observé. Dans ce cas, l'organe est subdivisé en un compartiment capillaire échangeant avec un compartiment tissulaire par une cinétique le plus souvent du premier ordre. Les résultats obtenus avec ce type de modèle sous-estiment le débit et ne permettent pas de prédire les premiers instants de la dynamique de répartition du traceur. Ces faiblesses ont été confirmées suite à l'amélioration de la résolution temporelle des tomographes, conduisant à l'élaboration de modèles incorporant plus de réalité physiologique. Cependant, tous ces modèles sont développés pour modéliser les échanges entre la micro-circulation et le tissu environnant à l'échelle d'un capillaire (échelle microscopique). Or la résolution spatiale des tomographes utilisés en clinique ne permet pas de distinguer la micro-circulation et le tissu. L'utilisation de ces modèles cinétiques avec des mesures de concentrations macroscopiques dépasse donc leur cadre théorique de validité et peut introduire des résultats faussés. Dans ce contexte, nous proposons un modèle cinétique basé sur le changement d'échelle (utilisant la méthode de prise de moyenne volumique). Ce changement d'échelle permet de remplacer l'ensemble micro-circulation/tissu par un volume fictif, homogène, dont les propriétés macroscopiques sont calculées à partir des propriétés microscopiques d'un Volume Elémentaire Représentatif (VER) du milieu. Dans un premier temps, afin de pouvoir comparer les résultats de ce modèle avec ceux du modèle compartimental standard, le VER considéré est constitué d'un capillaire unique et de son enveloppe de tissu, puis une complexité géométrique supplémentaire est introduite en considérant un réseau de capillaire isotrope à l'échelle de Darcy. Ces modèles sont utilisés pour identifier le débit à l'aide d'une méthode inverse. Pour cela, l'évolution temporelle du champ de concentration dans notre géométrie de référence, qui ne peut être mesurée par TEP en raison de sa faible résolution spatiale, est déterminée par des simulations numériques ainsi que par des mesures in vitro à l'aide d'un modèle expérimental, également développé au cours de ce travail, permettant de reproduire l'écoulement dans un canal traversant une matrice diffusante (gel d'alginate)Positron Emission Tomography (PET) provides a dynamic and space-resolved measurement of the concentration field of a radioactive tracer previously injected to the patient. Quantification of cerebral blood flow by PET is based on the use of a kinetic model linking cerebral blood flow to the spatial and temporal variations of tracer concentration in the brain. Various kinetic models have been proposed in the literature. However, most of the mare based on a compartmental approach of the observed organ In this case, the organ is divided in two compartments, the capillary and the tissue, and the exchanges between these two compartments are often described by a first order kinetic model. Results obtained with this kind of model under estimate the flow rate and are notable to predict the first instants of the tracer dynamics distribution. With the continuous improvement of the temporal resolution of PET, these weaknesses have been confirmed, which led to the development of models incorporating more physiological reality. However, all these models have been developed to describe exchanges between micro-circulation and surrounding tissue at the scale of capillary vessels (microscopic scale). Because the spatial resolution of PET inclinical practice is insufficient to allow the distinction between micro-circulation and tissue, using of these models with kinetic measurement of macroscopic concentrations exceeds their theoretical validity and can introduce false results. In this context, we propose a kinetic model based on up-scaling (using the method of volume averaging). This up-scaling technique allows to replace the two previous compartments (tissue and micro-circulation) by an homogeneous fictive volume, whose macroscopic properties are calculated from the microscopic properties of are presentative elementary volume (REV) of the medium. First, in order to compare the results of this model with those of the standard compartmental model, the considered REV consists of a single capillary and its surrounding tissue. Second, additional geometric complexity is introduced by considering an isotropic capillary network at the Darcy scale. These models are used to identify the flow rate using an inverse method. For that purpose, the temporal evolution of concentration field in a geometry of reference, which can't be measured by PET due to its low spatial resolution, is determined by numerical simulations and by in vitro measurements. These measurements are performed using an experimental model developed during this work to reproduce the flow in a channel passing through a diffusive matrix (alginate gel)
6
Kuznetsova, Alena. "Layered Double Hydroxides (LDH) as versatile nanoreservoirs for application in multi-functional coatings." Doctoral thesis, 2020. http://hdl.handle.net/10773/30586.
Full textAbstract:
The objective of the present work is synthesis and characterization of inorganic
nanoreservoirs based on layered double hydroxides (LDH) loaded with active
species, namely corrosion inhibitors and pH indicators. The most attractive
feature of LDH is the anion-exchange ability. Despite the countless studies that
describe the use of LDH for applications in protective coatings for anti-corrosion
applications, the study related to immobilization and consequent release of
anionic species is somewhat limited. Besides, there is still a lack of systematic
studies correlating the structure of nanocontainers with properties (release
profiles, triggering conditions) and the corresponding effect in coatings.
In this work, several methodologies were used for preparation of LDH.
Structure, morphology, colloidal and textural properties of resulting
nanocontainers have been characterized by X-ray diffraction (XRD), Fourier
transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM),
dynamic light scattering (DLS), thermogravimetric analysis (TG) and nitrogen
adsorption-desorption isotherms. Particular attention has been paid to the
release studies of active species immobilized in LDH, determination of
triggering conditions, establishment of kinetic models and definition of release
mechanisms by UV-Visible spectrophotometry. Additionally, the adsorption of
active species in LDH was investigated to understand how the active species
are immobilized during the synthesis, as well as for evaluation of its impact on
the application of nanoreservoirs in multi-functional coatings.
In general, the release of active species is rate-limited by diffusion with
possibility of anion-exchange reaction when anionic species are presenting in
the environment. However, the release profiles, extent of release and
adsorption of active species are strongly dependent on the method of synthesis
and on the structure and properties of the active species. In addition, the LDH
compositions studied were found to release the active species in response to
the presence of anions in solution (e.g. chlorides, hydroxides, carbonates),
even when the active species are not intercalated into the LDH galleries, but
adsorbed onto the external surface of the particles. Besides, the propensity of
LDH to dissolution or reaction under extreme pH conditions, in combination
with changes in the surface properties, can play a role in the agglomeration
and/or aggregation of the particles, thereby affecting adsorption and release of
different species.
Taking into account the properties of the materials obtained, it is possible to
conclude that several LDH compositions studied in this work are prospecting
additives for application in multi-functional coatings. Moreover, the present
work can be used as some sort of library of experimental data to support the
building and validation of computational models, to aid on the prediction of the
uptake and release of active species from LDH.O objetivo do presente trabalho consistiu na síntese e caracterização de nanoreservatórios inorgânicos baseados em hidróxidos duplos lamelares (HDL) com diferentes espécies ativas imobilizadas, nomeadamente inibidores de corrosão e indicadores de pH. Uma das características mais relevantes associada com o HDL é a sua capacidade de permuta aniónica. Apesar dos inúmeros trabalhos que descrevem a utilização do HDL para aplicações em revestimentos protetores contra a corrosão, o estudo relacionado com a imobilização e consequente libertação das espécies aniónicas é algo limitado. Além disso, não existem estudos sistemáticos na literatura que correlacionem a estrutura dos nanocontentores com as propriedades (perfis e condições de libertação controlada) e o efeito correspondente nos revestimentos. Neste trabalho, várias metodologias foram aplicadas para a preparação dos HDL. A estrutura, morfologia, propriedades coloidais e texturais dos nanocontentores resultantes foram caracterizadas por difração de raios-X (DRX), espectroscopia no infravermelho por transformada de Fourier (FTIR), microscopia eletrónica de varrimento (SEM), dispersão dinâmica de luz (DLS), análise termogravimétrica (TG) e isotérmicas de adsorção-desadsorção de azoto. Atenção especial foi prestada aos estudos de libertação de diferentes espécies ativas imobilizadas em HDL, nomeadamente as condições experimentais que podem levar à libertação das espécies ativas (ex.: pH, presença de sais), estabelecimento de modelos cinéticos e definição de mecanismos de libertação, recorrendo à espetrofotometria de UV-Visível. Além disso, o processo de adsorção de espécies ativas foi investigado para tentar perceber o que ocorre durante a síntese de diferentes composições de HDL bem como avaliar o impacto na aplicação prática de nanoreservatórios em revestimentos multifuncionais. Os resultados obtidos permitem concluir que, de forma geral, a libertação de espécies ativas é determinada pela difusão, com possibilidade de reação de permuta aniónica, quando espécies aniónicas estão presentes no ambiente. No entanto, os perfis de libertação, extensão da mesma e adsorção de espécies ativas em HDL dependem do método de síntese, bem como da estrutura e propriedades das espécies ativas. Igualmente relevante, é que as diferentes composições de HDL apresentam capacidade de libertar as espécies ativas imobilizadas em resposta à presença de aniões na solução (ex.: cloretos, hidróxidos, carbonatos), mesmo quando não intercaladas nas galerias do HDL, encontrando-se apenas adsorvidas na superfície externa do HDL. Além disso, a tendência dos materiais de HDL à dissolução ou reação sob condições extremas de pH, em combinação com alterações nas propriedades da superfície, tem influência no maior ou menor grau de aglomeração e/ou agregação das partículas, podendo afetar a adsorção e libertação das diferentes espécies. Atendendo às propriedades dos materiais obtidos, concluiu-se que vários HDL estudados são candidatos promissores para aplicação em revestimentos multifuncionais. Para além disso o presente trabalho pode ser usado como suporte na elaboração e validação de modelos computacionais que visam prever a captação e libertação de espécies ativas do HDL.
III Quadro Comunitário de Apoio
Programa Doutoral em Ciência e Engenharia de Materiais
Book chapters on the topic "In vitro release kinetic models"
1
Zhang, Bin, Haiteng Li, Shaokang Wang, Shahid Ahmed Junejo, Xingxun Liu, and Qiang Huang. "In Vitro Starch Digestion: Mechanisms and Kinetic Models." In Starch Structure, Functionality and Application in Foods, 151–67. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-0622-2_9.
Full text
2
Buckley, Stephen T., Kwang-Jin Kim, and Carsten Ehrhardt. "In Vitro Cell Culture Models for Evaluating Controlled Release Pulmonary Drug Delivery." In Controlled Pulmonary Drug Delivery, 417–42. New York, NY: Springer New York, 2011. http://dx.doi.org/10.1007/978-1-4419-9745-6_18.
Full text
3
Thorburn, Christine E., and Brian Slocombe. "The Use of In-Vitro Kinetic Models in the Evaluation of β-Lactam/β-Lactamase Inhibitor Combinations." In Advances in Experimental Medicine and Biology, 157–62. Boston, MA: Springer US, 1994. http://dx.doi.org/10.1007/978-1-4757-9206-5_16.
Full text
4
Owuor, James Jorum, Florence Oloo, Japheth Kibet Ngetich, Mwaiwa Kivunzya, Wesley Nyaigoti Omwoyo, and Jeremiah Waweru Gathirwa. "Comparison of Freeze and Spray Drying to Obtain Primaquine-Loaded Solid Lipid Nanoparticles." In Research Anthology on Synthesis, Characterization, and Applications of Nanomaterials, 288–304. IGI Global, 2021. http://dx.doi.org/10.4018/978-1-7998-8591-7.ch012.
Full textAbstract:
This article describes how the spray drying and freeze drying of various nanosized Solid Lipid Nanoparticle (SLN) and the physicochemical attributes of the acquired particles were examined. Primaquine loaded Solid Lipid Nanoparticles dried by the two strategies is examined. Particles were characterised by determination of size, drug loading, encapsulation efficiency and surface morphology. In vitro and kinetic drug discharge models were also considered. Preparation parameters have no impact on the molecule morphology and properties, and the main parameter deciding the molecule attributes in the drug substance of the nanoparticle, either in the spraying or in the freezing technique of drying. The drug release profile of spray dried SLN is superior to that of the freeze dried SLN.
5
Singhal, Peeush, Rajneesh Dutt Kaushik, and Vijay Jyoti Kumar. "Preparation and in vitro Characterisation of Solid Dispersion Floating Tablet by Effervescent Control Release Technique with Improved Floating Capabilities." In Molecular Pharmacology. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.92187.
Full textAbstract:
In this research, an effort has been done for the development of effervescent controlled release floating tablet (ECRFT) from solid dispersions (SDs) of diclofenac sodium (DS) for upsurge the solubility and dissolution rate. ECRFT of DS was prepared by using SDs of DS and its SDs prepared with PEG as carrier using thermal method (simple fusion). SDs of DS was formulated in many ratios (1:1, 1:2, 1:3 and 1:4). Prepared SDs were optimised for its solubility, % drug content and % dissolution studies. Tablets were formulated by using optimised SDs products and all formulation was evaluated for various parameters. A clear rise in dissolution rate was detected with entirely SD, amid that the optimised SD (SD4) was considered for ECRFT. Among all the tablet formulations, its F3 formulation was better in all the terms of pre-compression and post-compression parameters. It had all the qualities of a good ECRFT, based on this F3 formulation was selected as the best formulation. Data of in vitro release were fitted in several kinetics models to explain release mechanism. The F3 formulation shows zero order release. From this study, we can conclude that ECRFT containing SDs of DS can be successfully used for achieving better therapeutic objective.
6
Bin Zafar Auniq, Reedwan, Namon Hirun, and Upsorn Boonyang. "Three-Dimensionally Ordered Macroporous-Mesoporous Bioactive Glass Ceramics for Drug Delivery Capacity and Evaluation of Drug Release." In Ceramic Materials [Working Title]. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.95290.
Full textAbstract:
Bioactive glass ceramics (BGCs) have been used in orthopedic and dentistry due to having better osteoconductive and osteostimulative properties. This study aimed to evaluate and compare the drug release properties of two different BGCs; 45S5 and S53P4. The BGCs were composed with four phases of SiO2 – CaO – Na2O – P2O5 system, synthesized by sol–gel method using dual templates; a block-copolymer as mesoporous templates and polymer colloidal crystals as macroporous templates, called three-dimensionally ordered macroporous-mesoporous bioactive glass ceramics (3DOM-MBGCs). In vitro bioactivity test performed by soaking the 3DOM-MBGCs in simulated body fluid (SBF) at 37°C. The results indicated that, the 45S5 have the ability to grow hydroxyapatite-like layer on the surfaces faster than S53P4. Gentamicin drug was used to examine in vitro drug release properties in phosphate buffer solution (PBS). The amount of drug release was quantified through UV/Vis spectroscopy by using o-phthaldialdehyde reagent. S53P4 showed high drug loading content. The outcome of drug release in PBS showed that both S53P4 and 45S5 exhibited a slowly continuous gentamicin release. The resultant drug release profiles were fitted to the Peppas-Korsmeyer model to establish the predominant drug release mechanisms, which revealed that the kinetics of drug release from the glasses mostly dominated by Fickian diffusion mechanism.
7
Steensma, Aukje, Marcel J. B. Mengelers, Hub P. J. M. Noteborn, and Harry A. Kuiper. "Kinetic Models Describing In vitro Transport and Metabolism of Isoflavones and Their Glycosides in Human Caco-2 Cells." In Dietary Anticarcinogens and Antimutagens, 58–63. Elsevier, 2000. http://dx.doi.org/10.1533/9781845698188.2.58.
Full text
8
Drofenik, Mihael. "Thermodynamic Aspects of Homeopathy." In Alternative Medicine [Working Title]. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.94148.
Full textAbstract:
The well-known definition of disease, which Samuel Hahnemann presented in a tentative theory for his new science and art of healing, is used as the starting point for the thermodynamic model of homeopathy. The Le Chatelier principle was applied to the biochemical equilibrium compartmentalized in the individual human cells of an ill person to explain the curing based on the re-establishment of the starting equilibrium of a healthy person when using a remedy. It is revealed that a high dilution accompanied by succession is required to release the remedies to their constituent molecular species in order to increase their activity when taking part in the biochemical equilibrium that is essential for healing. In addition, a single remedy reaction-product species, when it is in excess, as well as satisfying the kinetic equilibrium, is a necessary and sufficient condition to force the new biochemical equilibrium in the direction of the basic original equilibrium associated with a healthy state. In addition, homeopathic aggravation is considered on the basis of the Law of Mass Action and the role of the small remedy concentration in some high-profile models is revisited. The second elementary law of homeopathy, the Law of the Infinitesimals, was explained based on a kinetic model. When a remedy occurs in the human cell of a healthy person and forms a reaction product (Simillimum) that induces the finest medical symptoms of an ill person, then remedies entering the cell of the ill person will form identical Simillimum molecules and re-establish the initial equilibrium of the healthy state and cure the ill person. However, this will also induce a molecular crowding in the cells of the ill person. For kinetic reasons, this will aggravate the re-establishment of the initial equilibrium and consequently worsen or even interrupt the medical treatment. At a low remedy concentration, the molecular crowding becomes negligible while the formation of the Simillimum and the re-establishment of the initial equilibrium will take place continuously and cure the person who is ill. The final understanding of the Simillimum in the thermodynamic model was illuminated and wide-opened its duality with the ill person’s key compound.
9
Gárate-Vélez, Lorena, Claudia Escudero-Lourdes, Daniela Salado-Leza, Armando González-Sánchez, Ildemar Alvarado-Morales, Daniel Bahena, Gladis Judith Labrada-Delgado, and José Luis Rodríguez-López. "Anthropogenic Iron Oxide Nanoparticles Induce Damage to Brain Microvascular Endothelial Cells Forming the Blood-Brain Barrier." In Advances in Alzheimer’s Disease. IOS Press, 2021. http://dx.doi.org/10.3233/aiad210010.
Full textAbstract:
Background: Iron nanoparticles, mainly in magnetite phase (Fe3O4 NPs), are released to the environment in areas with high traffic density and braking frequency. Fe3O4 NPs were found in postmortem human brains and are assumed to get directly into the brain through the olfactory nerve. However, these pollution-derived NPs may also translocate from the lungs to the bloodstream and then, through the blood-brain barrier (BBB), into the brain inducing oxidative and inflammatory responses that contribute to neurodegeneration. Objective: To describe the interaction and toxicity of pollution-derived Fe3O4 NPs on primary rat brain microvascular endothelial cells (rBMECs), main constituents of in vitro BBB models. Methods: Synthetic bare Fe3O4 NPs that mimic the environmental ones (miFe3O4) were synthesized by co-precipitation and characterized using complementary techniques. The rBMECs were cultured in Transwell® plates. The NPs-cell interaction was evaluated through transmission electron microscopy and standard colorimetric in vitro assays. Results: The miFe3O4 NPs, with a mean diameter of 8.45 ± 0.14 nm, presented both magnetite and maghemite phases, and showed super-paramagnetic properties. Results suggest that miFe3O4 NPs are internalized by rBMECs through endocytosis and that they are able to cross the cells monolayer. The lowest miFe3O4 NPs concentration tested induced mid cytotoxicity in terms of 1) membrane integrity (LDH release) and 2) metabolic activity (MTS transformation). Conclusion: Pollution-derived Fe3O4 NPs may interact and cross the microvascular endothelial cells forming the BBB and cause biological damage.
Conference papers on the topic "In vitro release kinetic models"
1
Blanco, Elvin, Takafumi Sangai, Funda Meric-Bernstam, and Mauro Ferrari. "Chemotherapeutic Synergy Enhancement Through Micellar Nanotherapeutics." In ASME 2010 First Global Congress on NanoEngineering for Medicine and Biology. ASMEDC, 2010. http://dx.doi.org/10.1115/nemb2010-13263.
Full textAbstract:
Current chemotherapeutic regimens involve the administration of a combination of agents with hopes of gaining synergistic cell-killing effects observed in vitro. However, drug synergy is rarely realized clinically given the different pharmacokinetic profiles of the drugs. Recent findings show that a combination of rapamycin and paclitaxel proves highly effective at hindering growth of tumors wherein the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. Our objective was to fabricate a micellar nanotherapeutic platform capable of delivering a multitude of agents shown to synergistically affect a specific pathway (PI3K/Akt/mTOR) in breast cancer. We hypothesized that this concomitant delivery strategy will result in increased antitumor efficacy, given the site-specific and controlled delivery of the two agents. Herein, we demonstrate the successful fabrication of a nanotherepeutic strategy for the treatment of breast tumors with aberrant PI3K/Akt/mTOR pathways. Resulting polymer micelles were small in size (∼30 nm) and showed high levels of drug incorporation efficiency of both rapamycin and paclitaxel. Current studies involve the examination of release kinetics and antitumor efficacy in in vitro and in vivo models.
2
Mendygarin, Yertay, Luis R. Rojas-Solórzano, Nurassyl Kussaiyn, Rakhim Supiyev, and Mansur Zhussupbekov. "Eulerian-Eulerian Multiphase Modeling of Blood Cells Segregation in Flow Through Microtubes." In ASME 2017 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2017. http://dx.doi.org/10.1115/imece2017-70850.
Full textAbstract:
Cardiovascular Diseases, the common name for various Heart Diseases, are responsible for nearly 17.3 million deaths annually and remain the leading global cause of death in the world. It is estimated that this number will grow to more than 23.6 million by 2030, with almost 80% of all cases taking place in low and middle income countries. Surgical treatment of these diseases involves the use of blood-wetted devices, whose relatively recent development has given rise to numerous possibilities for design improvements. However, blood can be damaged when flowing through these devices due to the lack of biocompatibility of surrounding walls, thermal and osmotic effects and most prominently, due to the excessive exposure of blood cells to shear stress for prolonged periods of time. This extended exposure may lead to a rupture of membrane of red blood cells, resulting in a release of hemoglobin into the blood plasma, in a process called hemolysis. Moreover, exposure of platelets to high shear stresses can increase the likelihood of thrombosis. Therefore, regions of high shear stress and residence time of blood cells must be considered thoroughly during the design of blood-contacting devices. Though laboratory tests are vital for design improvements, in-vitro experiments have proven to be costly, time-intensive and ethically controversial. On the other hand, simulating blood behavior using Computational Fluid Dynamics (CFD) is considered to be an inexpensive and promising tool to help predicting blood damage in complex flows. Nevertheless, current state-of-the-art CFD models of blood flow to predict hemolysis are still far from being fully reliable and accurate for design purposes. Previous work have demonstrated that prediction of hemolysis can be dramatically improved when using a multiphase (i.e., phases are plasma, red blood cells and platelets) model of the blood instead of assuming the blood as a homogeneous mixture. Nonetheless, the accurate determination of how the cells segregate becomes the critical issue in reaching a truthful prediction of blood damage. Therefore, the attempt of this study is to develop and validate a numerical model based on Granular Kinetic Theory (GKT) for solid phases (i.e., cells treated as particles) that provides an improved prediction of blood cells segregation within the flow in a microtube. Simulations were based on finite volume method using Eulerian-Eulerian modeling for treatment of three-phase (liquid-red blood cells and platelets) flow including the GKT to deal with viscous properties of the solid phases. GKT proved to be a good model to predict particle concentration and pressure drop by taking into account the contribution of collisional, kinetic and frictional effects in the stress tensor of the segregated solid phases. Preliminary results show that the improved segregated model leads to a better prediction of spatial distribution of blood cells. Simulations were performed using ANSYS FLUENT platform.
3
Berchane, Nader S., Kenneth H. Carson, Allison C. Rice-Ficht, and Malcolm J. Andrews. "Investigation of Drug Release From Biodegradable PLG Microspheres: Experiment and Theory." In ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-176030.
Full textAbstract:
Piroxicam containing PLG microspheres having different size distributions were fabricated, and in vitro release kinetics were determined for each preparation. Based on the experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the system size was increased. The mathematical model gave a good fit to the experimental release data.
4
Som, S., Z. Wang, W. Liu, and D. E. Longman. "Comparison of Different Chemical Kinetic Models for Biodiesel Combustion." In ASME 2013 Internal Combustion Engine Division Fall Technical Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/icef2013-19094.
Full textAbstract:
The current study compares the predictions by four different published mechanisms in literature which have been used for 3 dimensional compression ignition engine simulations. These four mechanisms use two different sets of surrogates: (a) methyl decanoate, methyl 9-decenoate, and n-heptane, (b) methyl butanoate and n-heptane. The mechanisms include: (1) 115 species and 460 reactions [1] using surrogate mixture (a); (2) 77 species and 209 reactions [2] using surrogate mixture (a); (3) 145 species and 869 reactions [3] using surrogate mixture (b); (4) 41 species and 150 reactions [4] using surrogate mixture (b). The different reduction techniques implemented to obtain the reduced mechanisms from the detailed mechanisms are briefly described. The surrogate mixture compositions are then modified to match the cetane number of the real biodiesel fuels. The experimental data for comparison include jet-stirred reactor data for species concentrations for biodiesel derived from rapeseed oil and 3 dimensional constant volume combustion data (for ignition, combustion, and emission characteristics), engine data (for pressure, heat release rate, and emission characteristics) for soy-derived biodiesel. 0-D and 3-D constant volume simulations with all the mechanisms can capture the general experimental trends quite well. Large surrogate models and mechanisms tend to provide better predictions at the expense of increased computational costs. The 115 species and 460 reaction mechanism was observed to perform the best among the mechanisms in predicting the jet-stirred reactor and 3-D constant volume data. It was observed that all the mechanisms are able to qualitatively capture the engine performance and emission characteristics.
5
Kluge, Jonathan A., Rudra A. Pampati, Mara L. Schenker, Daniel J. Zhou, John E. Esterhai, David L. Kaplan, and Robert L. Mauck. "Delivery of Active FGF-2 From Mechanically-Stable Biological Nanofibers Accelerates Cell Ingress Into Multifiber Composites." In ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53955.
Full textAbstract:
Fibrocartilaginous tissues such as the meniscus and annulus fibrosus serve critical load-bearing roles, relying on arrays of highly organized collagen fibers to resist tensile loads [1]. As these specialized structures are often injured, there exists great demand for engineered tissues for repair or replacement. Cell-laden aligned nanofibrous scaffolds formed from poly(ε-caprolactone) (PCL) have shown promise in achieving tissuelike mechanical and biochemical properties and can direct cellular and matrix organization in vitro [2]. A current limitation of nanofibrous scaffolds, however, is a slow rate of cellular infiltration, particularly in thick scaffolds. To address this, dynamic composite nanofibrous scaffolds have been fabricated via multi-fiber spinning [3], which can offer tunable modes of degradation depending on the polymer sources. For example, water-soluble polyethylene oxide (PEO) fibers can be co-spun with PCL to improve porosity and hasten cell ingress [4]. Incorporation of additional tunable and bioactive polymer sources may add greater versatility to these composite systems. For example, aqueous-based silk fibroin can be used as a slow-degrading, mechanically strong composite fiber component [5] into which active biologic factors (drugs, growth factors) can be incorporated [6]. Variably-degradable silk fibers can be formed by modulating post-spinning treatments, and protein release kinetics can likewise be manipulated by the physical crosslinking method [7]. We hypothesized that incorporation of robust and tunable silk protein-based fibers into a composite of slow-degrading synthetic fibers would provide mechanical function while delivering active biologic factors to expedite cell proliferation and encourage more rapid construct colonization. To test this hypothesis, we characterized the release kinetics of recombinant FGF-2 from silk fibers and its bioactivity in vitro and in a rat subcutaneous implant model.
6
Bass, Joseph L., and Eric P. Fahrenthold. "A Kinetic Formulation of Reacting Molecular Dynamics." In ASME 2016 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2016. http://dx.doi.org/10.1115/imece2016-65451.
Full textAbstract:
Macroscale, mesoscale, and ab initio models of reacting shock physics are based, in their most general forms, on rate law descriptions of the chemical processes of interest. Reacting molecular dynamics simulations, by contrast, typically employ potential functions to model chemical reactions. An alternative reacting molecular dynamics formulation, employing nonholonomic Hamiltonian methods, models bonding-debonding as a kinetic process. Simulation results using this method are compared with experiment, for energy release and detonation products in HMX. The molecular dynamics simulations may be used to develop a macroscale, adiabatic model of the detonation chemistry.
7
Zhou, Apeng, Shirin Jouzdani, and Ben Akih-Kumgeh. "Reduced Chemical Kinetic Models of C1 - C4 Alcohols Using the Alternate Species Elimination Approach." In ASME 2019 Internal Combustion Engine Division Fall Technical Conference. American Society of Mechanical Engineers, 2019. http://dx.doi.org/10.1115/icef2019-7114.
Full textAbstract:
Abstract This study presents four separate reduced chemical kinetic models of methanol/ethanol, propanol isomers, n- and iso-butanol, and n- and s-butanol isomers, derived from a comprehensive chemical kinetic model of C1-C5 alcohols using the Alternate Species Elimination approach. It is motivated by complexity of the detailed model (comprising 600 species and 4100 elementary reactions) and the need for simpler kinetic models for analysis of combustion of smaller alcohols. The reduced models are obtained on the basis of ignition delay time simulations with imposed thresholds on the resulting normalized changes in ignition delay times. The following reduced models are obtained: methanol/ethanol: 38 species and 197 reactions; propanol isomers: 68 species and 419 reactions; n- and iso-butanol: 140 species and 745 reactions; and n- and s-butanol: 134 species and 739 reactions. Predictions of ignition delay times by the reduced models are found to be in good with the detailed models. The reduced models are further tested against other relevant combustion properties. These properties include burning velocities of laminar premixed flames, global pyrolysis time scales, and heat release timing in Homogeneous Charge Compression Ignition engines. This verification shows that reduced models can replace the comprehensive model in combustion analysis without loss of predictive performance. The reduced models can also serve as starting models for developing combined chemical kinetic models of gasoline/diesel and alcohol blends.
8
Banerjee, Siddhartha, Nidheesh Bharadwaj, and Christopher J. Rutland. "Investigation of In-Cylinder Mixing Using Large Eddy Simulation Models for LTC Diesel Applications." In ASME 2009 Internal Combustion Engine Division Spring Technical Conference. ASMEDC, 2009. http://dx.doi.org/10.1115/ices2009-76031.
Full textAbstract:
In-cylinder mixture preparation and early combustion heat release are studied using Large Eddy Simulation (LES) for direct injection (DI) diesel with high exhaust gas recirculation (EGR) and early injection timing. Both LES and traditional Reynolds Average Navier-Stokes (RANS) calculations are carried out using KIVA-3V release 2 and compared with experimental results of medium load LTC-diesel (Low Temperature Combustion) cases. Simulations presented in this paper are carried out using KH-RT (Kelvin Helmholtz – Rayleigh Taylor) breakup model for spray atomization and CHEMKIN n-heptane mechanism for combustion and both dynamic structure LES and RNG (re-normalized group) kε RANS for turbulence model. Although engine simulation using LES model poses significant challenges on practical engine grids, significant agreement with LTC-diesel experiments is observed by using an additional spray source term for modeling the effect of liquid sprays on sub-grid kinetic energy transport calculation in engines. Results when compared to RANS, demonstrate that LES is able to predict local spots of early heat release resulting in more accurate prediction of start of combustion timing and early heat release phasing. Mixing due to bulk fluid motion such as swirl is also observed more distinctively in LES calculations.
9
Nontasirichayakul, Chanicha, Chutima Wiranidchapong, Worapan Sithithaworn, and Duangratana Shuwisitkul. "Optimization of Formulation Variables Using Central Composite Design to Enhance Andrographolide Release from <i>Andrographis paniculata</i> Extract-Chitosan Solid Dispersion." In 5th International Conference and Exhibition on Pharmaceutical Sciences and Technology 2022. Switzerland: Trans Tech Publications Ltd, 2022. http://dx.doi.org/10.4028/p-3xj8r7.
Full textAbstract:
Andrographolide (AGP), a major component of Andrographis paniculata (Burm.f.) Nees (AP), has several biological activities. Nevertheless, poorly water solubility and low bioavailability of AGP lead to decrease clinical benefits. Therefore, this study aims to develop of AP extract-chitosan solid dispersion using central composite design (CCD) to enhance AGP release. AP crude extract was obtained by Soxhlet extractor using 85%v/v ethanol as a solvent extraction. Then, AP extract, chitosan, and poloxamer 188 in the concentrations provided by CCD was spray dried. The in-vitro release of AP extract-chitosan spray dried powder was studied by dissolution equipped with enhancer cell in 200 ml of 50%v/v methanol at 37°C and 50 rpm of paddle speed. Samples were withdrawn at 0.25-96 hours and then determined AGP by UV spectrophotometer at 224 nm. The results of CCD indicated that %ethanol and %AGP from concentrated AP extract had significant (P < 0.05) effect on the concentration of AGP released at 5 hours. The optimum formulation composed of %ethanol of 18.25, %AGP in extract of 0.38, and %poloxamer 188 of 0.17 resulted in more AGP concentration at 5 hours than 50 μg/mL. Release kinetic study revealed that %release of the optimal formulation was best fitted to first order kinetic. In powder X-ray diffraction, intensity of AGP characteristic peaks in the optimal formulation decreased by 7.17-25.69 times compared with AGP standard. It was concluded that the optimal formulation of AP extract-chitosan solid dispersion could improve AGP release due to changing crystalline AGP to amorphous state.
10
Jen, Chun-Ping, and Neng-Chuan Tien. "Investigation of Colloid-Facilitated Effects on the Radionuclides Migration in the Fractured Rock With a Kinetic Solubility-Limited Dissolution Model." In ASME 2010 13th International Conference on Environmental Remediation and Radioactive Waste Management. ASMEDC, 2010. http://dx.doi.org/10.1115/icem2010-40001.
Full textAbstract:
Nuclides can move with the groundwater either as solutes or colloids, where the latter mechanism generally results in much shorter traveling time as they interact strongly with solid phases, such as actinides. It is therefore essential to assess the relative importance of these two transport mechanisms for different nuclides. The relative importance of colloids depends on the nature and concentration of colloids in groundwater. Plutonium (Pu), neptunium (Np), uranium (U) and americium (Am) are four nuclides of concern for long-term emplacement of nuclear wastes at potential repository sites. If attached to iron oxide, clay or silica colloids in groundwater. Strong sorption of the actinides by colloids in groundwater may facilitate transport of these nuclides along potential flow paths. Solubility-limited dissolution model models can be used to determine the release of the safety assessment for nuclear waste in geological disposal sites. The present study investigates the effect of colloid on the transport of solubility limited nuclide under the kinetic solubility limited dissolution (KSLD) boundary condition in fractured media. The release rate of nuclide would proportional to the difference between the saturation concentration and the inlet aqueous concentration of nuclide. The presence of colloids could decrease the aqueous concentration of nuclide and thus could increase the release flux of nuclide from the waste form.
Reports on the topic "In vitro release kinetic models"
1
Spiers, Donald, Arieh Gertler, Harold Johnson, and James Spain. An In Vitro and In Vivo Investigation of the Diverse Biological Activities of Bovine Placental Lactogen. United States Department of Agriculture, August 1993. http://dx.doi.org/10.32747/1993.7568087.bard.
Full textAbstract:
In order to understand the structure-function relationship of bovine placental lactogen (bPL) and initiate production of material for in vivo testing, 28 different bPL analogues were prepared by either truncation or site-directed mutagenesis. The effect of these mutations was determined by measuring binding capacity, ability to homodimerize extracellular domains (ECDs) of several lactogenic and somatogenic receptors, and by in vitro bioassays. Two analogues were prepared in large amounts for in vivo studies. These studies (a) identified the residues responsible for the somatogenic activity of bPL (K73, G133, T188) and for both lactogenic and somatogenic activity (N-terminus, K185, Y190); (b) allowed preparation of bPL analogues with selectively abolished or reduced somatogenic activity; and (c) provided a tool to understand the kinetic difference between lactogenic and somatogenic receptors. In vivo studies using rodent and dairy models showed that bovine growth hormone (bGH) is superior to bPL in stimulating growth and lactation. Likewise, bGH has greater somatogenic activity in different age groups and thermal environments. Initial studies of bPL analog T188 suggest that its lactogenic potential is superior to bGH. Effective experimental models have now been developed and tested for analysis of new bPL analogs.