Relevant bibliographies by topics / Subcutaneous delivery

Academic literature on the topic 'Subcutaneous delivery'

Author: Grafiati
Published: 10 December 2022
Last updated: 29 January 2023

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Journal articles on the topic "Subcutaneous delivery"

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Dychter, Samuel S., David A. Gold, and Michael F. Haller. "Subcutaneous Drug Delivery." Journal of Infusion Nursing 35, no. 3 (2012): 154–60. http://dx.doi.org/10.1097/nan.0b013e31824d2271.

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Benagiano, Giuseppe, Henry Gabelnick, and Manuela Farris. "Contraceptive devices: subcutaneous delivery systems." Expert Review of Medical Devices 5, no. 5 (September 2008): 623–37. http://dx.doi.org/10.1586/17434440.5.5.623.

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Houtzagers, C. M. G. J. "Subcutaneous Insulin Delivery: Present Status." Diabetic Medicine 6, no. 9 (December 1989): 754–61. http://dx.doi.org/10.1111/j.1464-5491.1989.tb01274.x.

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Selvaraj, Jothy, Graham Rhall, Mounir Ibrahim, Talat Mahmood, Nigel Freeman, Zennon Gromek, Grant Buchanan, Farhan Syed, Hany Elsaleh, and Ben J. C. Quah. "Custom-designed Small Animal focal iRradiation Jig (SARJ): design, manufacture and dosimetric evaluation." BJR|Open 2, no. 1 (November 2020): 20190045. http://dx.doi.org/10.1259/bjro.20190045.

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Objective: Preclinical animal models allow testing and refinement of novel therapeutic strategies. The most common preclinical animal irradiators are fixed source cabinet irradiators, which are vastly inferior to clinical linear accelerators capable of delivering highly conformal and precise treatments. The purpose of this study was to design, manufacture and test an irradiation jig (small animal focal irradiation jig, SARJ) that would enable focal irradiation of subcutaneous tumours in a standard fixed source cabinet irradiator. Methods and materials: A lead shielded SARJ was designed to rotate animal holders about the longitudinal axis and slide vertically from the base plate. Radiation dosimetry was undertaken using the built-in ion chamber and GAFChromic RTQA2 and EBT-XD films. Treatment effectiveness was determined by irradiating mice with subcutaneous melanoma lesions using a dose of 36 Gy in three fractions (12 Gy x 3) over three consecutive days. Results: The SARJ was tested for X-ray shielding effectiveness, verification of dose rate, total dose delivered to tumour and dose uniformity. Accurate and uniform delivery of X-ray dose was achieved. X-ray doses were limited to the tumour site when animal holders were rotated around their longitudinal axis to 15o and 195o, allowing sequential dose delivery using parallel-opposed tangential beams. Irradiation of subcutaneous melanoma tumour established on the flanks of mice showed regression. Conclusion: SARJ enabled delivery of tangential parallel-opposed radiation beams to subcutaneous tumours in up to five mice simultaneously. SARJ allowed high throughput testing of clinically relevant dose delivery using a standard cabinet-style fixed source irradiator. Advances in knowledge: A custom designed jig has been manufactured to fit into conventional cabinet irradiators and is dosimetrically validated to deliver clinically relevant dose distributions to subcutaneous tumours in mice for preclinical studies.
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Mapletoft, John W., Laura Latimer, Lorne A. Babiuk, and Sylvia van Drunen Littel-van den Hurk. "Intranasal Immunization of Mice with a Bovine Respiratory Syncytial Virus Vaccine Induces Superior Immunity and Protection Compared to Those by Subcutaneous Delivery or Combinations of Intranasal and Subcutaneous Prime-Boost Strategies." Clinical and Vaccine Immunology 17, no. 1 (October 28, 2009): 23–35. http://dx.doi.org/10.1128/cvi.00250-09.

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ABSTRACT Bovine respiratory syncytial virus (BRSV) infects cells of the respiratory mucosa, so it is desirable to develop a vaccination strategy that induces mucosal immunity. To achieve this, various delivery routes were compared for formalin-inactivated (FI) BRSV formulated with CpG oligodeoxynucleotide (ODN) and polyphosphazene (PP). Intranasal delivery of the FI-BRSV formulation was superior to subcutaneous delivery in terms of antibody, cell-mediated, and mucosal immune responses, as well as reduction in virus replication after BRSV challenge. Although intranasal delivery of FI-BRSV also induced higher serum and lung antibody titers and gamma interferon (IFN-γ) production in the lungs than intranasal-subcutaneous and/or subcutaneous-intranasal prime-boost strategies, no significant differences were observed in cell-mediated immune responses or virus replication in the lungs of challenged mice. Interleukin 5 (IL-5), eotaxin, and eosinophilia were enhanced after BRSV challenge in the lungs of subcutaneously immunized mice compared to unvaccinated mice, but not in the lungs of mice immunized intranasally or through combinations of the intranasal and subcutaneous routes. These results suggest that two intranasal immunizations with FI-BRSV formulated with CpG ODN and PP are effective and safe as an approach to induce systemic and mucosal responses, as well to reduce virus replication after BRSV challenge. Furthermore, intranasal-subcutaneous and subcutaneous-intranasal prime-boost strategies were also safe and almost as efficacious. In addition to the implications for the development of a protective BRSV vaccine for cattle, formulation with CpG ODN and PP could also prove important in the development of a mucosal vaccine that induces protective immunity against human RSV.
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Yamasaki, Yoshimitsu. "Subcutaneous and transmucosal delivery of insulin." Drug Delivery System 15, no. 6 (2000): 525–32. http://dx.doi.org/10.2745/dds.15.525.

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Jones, Graham B., David S. Collins, Michael W. Harrison, Nagarajan R. Thyagarajapuram, and Justin M. Wright. "Subcutaneous drug delivery: An evolving enterprise." Science Translational Medicine 9, no. 405 (August 30, 2017): eaaf9166. http://dx.doi.org/10.1126/scitranslmed.aaf9166.

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Yang, M. X., B. Shenoy, M. Disttler, R. Patel, M. McGrath, S. Pechenov, and A. L. Margolin. "Crystalline monoclonal antibodies for subcutaneous delivery." Proceedings of the National Academy of Sciences 100, no. 12 (June 2, 2003): 6934–39. http://dx.doi.org/10.1073/pnas.1131899100.

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Anderson, David R., Jeffrey S. Ginsberg, Robert Burrows, and Pat Brill-Edwards. "Subcutaneous Heparin Therapy during Pregnancy: a Need for Concern at the Time of Delivery." Thrombosis and Haemostasis 65, no. 03 (1991): 248–50. http://dx.doi.org/10.1055/s-0038-1647659.

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SummarySubcutaneous heparin is the treatment of choice for women requiring anticoagulant therapy during pregnancy. However, heparin therapy presents a management problem at delivery because of its potential to cause a persistent anticoagulant effect and thus increase the risk of bleeding. In order to avoid therapeutic complications it has been our practice to have women eithei discontinue their heparin injections with the onset of labour or to terminate heparin injections 12 h prior to elective induction. To determine the safety of our anticoagulant protocol at delivery we reviewed consecutive patients treated with subcutaneous heparin therapy during pregnarcl, at our centre. Over a 23 month period we found that six of 11 women receiving subcutaneous heparin during pregnancy delivered while their aPTT was prolonged. In addition, three women received intravenous protamine sulphate prior to delivery and in one patient major bleeding occurred during an emergency cesarean section. Those women who had elevated aPTTs at the time of delivery all gave birth within 28 h of their last injection of heparin. In order to avoid a prolonged aPTT at delivery, we have now adopted a more conservative approach to the management of subcutaneous heparin use at term. Subcutaneous heparin is discontinued 24 h prior to commencing an elective induction of labour.
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Dirnena-Fusini, Ilze, Marte Kierulf Åm, Anders Lyngvi Fougner, Sven Magnus Carlsen, and Sverre Christian Christiansen. "Intraperitoneal, subcutaneous and intravenous glucagon delivery and subsequent glucose response in rats: a randomized controlled crossover trial." BMJ Open Diabetes Research & Care 6, no. 1 (November 2018): e000560. http://dx.doi.org/10.1136/bmjdrc-2018-000560.

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ObjectiveHypoglycemia is a frequent and potentially dangerous event among patients with diabetes mellitus type 1. Subcutaneous glucagon is an emergency treatment to counteract severe hypoglycemia. The effect of intraperitoneal glucagon delivery is sparsely studied. We performed a direct comparison of the blood glucose response following intraperitoneally, subcutaneously and intravenously administered glucagon.Research design and methodsThis is a prospective, randomized, controlled, open-label, crossover trial in 20 octreotide-treated rats. Three interventions, 1 week apart, in a randomized order, were done in each rat. All 20 rats were given intraperitoneal and subcutaneous glucagon injections, from which 5 rats were given intravenous glucagon injections and 15 rats received placebo (intraperitoneal isotonic saline) injection. The dose of glucagon was 5 µg/kg body weight for all routes of administration. Blood glucose levels were measured before and until 60 min after the glucagon/placebo injections.ResultsCompared with placebo-treated rats, a significant increase in blood glucose was observed 4 min after intraperitoneal glucagon administration (p=0.009), whereas after subcutaneous and intravenous glucagon administration significant increases were seen after 8 min (p=0.002 and p<0.001, respectively). In intraperitoneally treated compared with subcutaneously treated rats, the increase in blood glucose was higher after 4 min (p=0.019) and lower after 40 min (p=0.005) and 50 min (p=0.011). The maximum glucose response occurred earlier after intraperitoneal compared with subcutaneous glucagon injection (25 min vs 35 min; p=0.003).ConclusionsGlucagon administered intraperitoneally gives a faster glucose response compared with subcutaneously administered glucagon in rats. If repeatable in humans, the more rapid glucose response may be of importance in a dual-hormone artificial pancreas using the intraperitoneal route for administration of insulin and glucagon.
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Dissertations / Theses on the topic "Subcutaneous delivery"

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Al, Kurdi Zakieh. "Subcutaneous and oral delivery of insulin." Thesis, University of Greenwich, 2015. http://gala.gre.ac.uk/18146/.

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The aim of this project was to prepare, optimize, characterize and compare a subcutaneous/oral delivery system for insulin. The effect of various low molecular weight chitosans (LMWCs) on the stability of insulin, using USP HPLC methods, was investigated. Insulin was found to be stable in a polyelectrolyte complex (PEC) consisting of insulin and LMWC in the presence of Tris-buffer at pH 6.5. In the presence of LMWC, the stability of insulin increased with decreasing molecular weight of LMWC; 13 kDa LMWC was the most efficient molecular weight for enhancing the physical and chemical stability of insulin. The bioactivity of insulin in the PEC was assessed using enzyme-linked immunosorbent assay (ELISA) testing; results showed that insulin is still functionally active in the presence of chitosan. Solubilization of the PEC in a reverse micelle formulation (RMF) and administration to diabetic rats resulted in an oral delivery system for insulin with acceptable bioactivity. The effect of reduced (GSH) and oxidized (GSSG) glutathione on the bioactivity of insulin was studied. A PEC of insulin with low molecular weight chitosan (13 kDa) was prepared and characterized. The PEC was then solubilized, in the presence and absence of GSH and GSSG, in a reverse micelle consisting of oleic acid and two surfactants (labrasol and plurol). The in vitro and in vivo performances of the reverse micelle formulations (RMFs) were evaluated in rats. At pH 6.5 the association efficiency of the PEC was 76.2%. In vitro insulin release from the RMs was negligible at pH 1.2 and was markedly increased at pH 6.8. The hypoglycemic activity of insulin in the PEC was reduced when administered via the subcutaneous route, regardless of the GSH content. On the other hand, the presence of GSSG significantly enhanced hypoglycaemia. When the RMF was administered via the oral route, the presence of GSH had no effect on the hypoglycemic activity of insulin compared with the GSH free system. However, the presence of GSSG in the oral preparation increased the hypoglycemic activity of insulin; probably by inhibiting insulin degradation, thereby prolonging its effect. Thus, incorporation of GSSG in the RMF reduces blood glucose levels in rats and protects insulin from degradation. The effect of glucosamine HCl (GlcN⋅HCl) on the bioactivity of insulin, administered via subcutaneous (SC) and oral routes, in rats was also investigated. The oral insulin delivery system (IC-RM) was prepared by solubilizing insulin-chitosan (13 kDa) polyelectrolyte complex (IC-PEC) in a RM system consisting of oleic acid, PEG-8 caprylic/capric glycerides and polyglycerol-6-dioleate. The blood glucose levels were measured using a blood glucose meter. The results revealed that the extent of hypoglycemic activity of SC insulin was GlcN⋅HCl dose dependent when they were administered simultaneously. A significant reduction in blood glucose level (p < 0.05) was found for the insulin:GlcN⋅HCl at mass ratios of 1:10 and 1:20, whereas lower ratios (e.g. 1:1 and 1:4) showed no significant reduction. Furthermore, enhancement of the action of SC insulin was achieved by oral administration of GlcN⋅HCl for five consecutive days prior to insulin injection (p < 0.05). For oral insulin administration via the IC-RM system, the presence of GlcN-HCl increased the hypoglycemic activity of insulin (p < 0.05). The relative pharmacological availabilities (PA) were 6.7% and 5.4% in the presence and absence of GlcN⋅HCl (i.e. the increase in the relative PA was about 23% due to the incorporation of GlcN⋅HCl in the IC-RM system), respectively. The aforementioned findings offer an opportunity to incorporate GlcN⋅HCl in oral insulin delivery systems in order to enhance a reduction in blood glucose levels.
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Faraji-Rad, Zahra. "Microneedles fabrication for subcutaneous fluid sampling and drug delivery." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/6734/.

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Microneedle arrays have been proposed for drug delivery and point-of-care diagnostics to improve the quality of health care delivery systems. Unskilled and painless applications of microneedle patches for blood collection or drug delivery are two of the advantages of microneedle arrays over hypodermic needles. Microneedle designs which range from sub-micron to millimetres feature sizes are fabricated using the tools of the microelectronics industry from materials such as metals, silicon, and polymers. However, to date, large-scale manufacture of microneedles has been limited because of the high cost and complexity of microfabrication techniques. This thesis aims to develop new manufacturing methods that may overcome the complexity of microneedle fabrication and scale-up problems. Three different microfabrication methods were investigated. (1) Silicon microneedles were manufactured through deep reactive ion etching (DRIE) with variable heights and tip sharpness. A series of experiments were also performed to investigate the influence of design and process parameters on the fabrication outcomes. (2) Plastic microneedle arrays were fabricated by three-dimensional (3D) printing. (3) A great variety of microneedle array geometries were manufactured using 3D laser lithography. The novel microneedle array design and fabrication technique proposed in this thesis may facilitate the manufacture of low-cost patches for drug delivery and collection of subcutaneous capillary blood or interstitial fluid.
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Deadman, Claire Michelle. "Biopharmaceutical studies of slow release, subcutaneous polymeric drug delivery systems." Thesis, University College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.433154.

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Marquette, Sarah. "Stabilization and development of sustained-release formulations of protein/antibody for subcutaneous delivery." Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209251.

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ABSTRACT

This project aimed at developing a drug delivery system (DDS) able to enhance the stability and

residence time in vivo of antibodies (Abs). The system will deliver drug by the subcutaneous

route (SC), while ensuring accurate control of the drug release and the resulting plasmatic level. This technology platform will allow to reduce frequency of injection, potentially decrease side effects and maintain high concentration of Abs which will improve life of patient having chronic disease such as autoimmune and inflammatory disease. Biodegradable synthetic polymer-based formulations (polylactide-co-glycolide (PLGA)) were selected as carriers for encapsulated Abs. This was because they offer good protection for the Abs and allow sustained release of the Abs for a controlled period of time. After the evaluation of different encapsulation methods such as the water-oil-in-water (w/o/w) and the solid-in-oil-inwater

(s/o/w) processes, the encapsulation of the Ab in solid state (s/o/w) appeared to be more appropriate for producing Ab-loaded PLGA microspheres (MS). It allowed us to maintain the

Ab in a monomeric conformation and to avoid the formation of unsoluble aggregates mainly present at the water/oil interface. The first part of the project was the optimization of both the method for producing the Ab solid particles (spray-drying process) and the encapsulation of these Ab solid particles into the polymeric MS (s/o/w process) by design of experiment (DoE). These optimizations were carried out using a bovine polyclonal immunoglobulin G (IgG) as model molecule. In further optimization of the spray-drying process by (DoE), aqueous Ab solutions were spray-dried using a mini Spray-Dryer assembly with a 0.7 mm spray nozzle. In accordance with the particle size (d(0.5) ~5 μm), the stability (no loss of monomer measured by

size exclusion chromatography (SEC) and the yield of the spray-drying process (> 60 % w/w), the process parameters were set of follow: 3 mL/min as liquid feed flow rate, 130°C /75°C as inlet temperature (inlet T°) / outlet temperature (outlet T°), 800 L/h as atomization flow rate and

30 m3/h as drying air flow rate. For the s/o/w, the methylene chloride (MC) commonly used for

an encapsulation process was replaced by ethyl acetate (EtAc), which was considered as a more

suitable organic solvent in terms of both environmental and human safety. The effects of several processes and formulation factors were evaluated on IgG:PLGA MS properties such as: particle size distribution, drug loading, IgG stability, and encapsulation efficiency (EE%). Several formulations and processing parameters were also statistically identified as critical to get reproducible process (e.g. the PLGA concentration, the volume of the external phase, the emulsification rate, and the quantity of IgG microparticles). The optimized encapsulation

method of the IgG has shown a drug loading of up to 6 % (w/w) and an encapsulation efficiency

of up to 60 % (w/w) while preserving the integrity of the encapsulated antibody. The produced MS were characterized by a d(0.9) lower than 110 μm and showed burst effect lower than 50 %(w/w). In the second part of the project, the optimized spray-drying and s/o/w processes

developed with the IgG were applied to a humanized anti-tumor necrosis factor (TNF) alpha

MAb to confirm the preservation of the MAb activity during these processes. The selected s/o/w method allowed us to produce MAb-loaded PLGA MS with an appropriate release profile up to 6 weeks and MAb stability. In order to maintain the Abs’ activity, both during encapsulation and

dissolution, the addition of a stabilizer such as trehalose appeared to be crucial, as did the

selection of the PLGA. It was demonstrated that the use of a PLGA characterized by a 75:25

lactide:glycolide (e.g. Resomer ® RG755S) ratio decreased the formation of low molecular weight species during dissolution, which led to preserve Abs activity through its release from the

delivery system. Furthermore, the release profile was adjusted according to the type of polymer

and its concentration. E.g. 10 % w/v RG755S allowed Ab MS with a release time of 6 weeks to

be obtained. The optimization of both the formulation and the encapsulation process allowed

maximum 13 % w/w Ab-loaded MS to be produced. It was demonstrated that the Ab-loaded PLGA MS were stable when stored at 5°C for up to 12 weeks and that the selection of the appropriate type of PLGA was critical to assuring the stability of the system. The better stability observed when using a PLGA characterized by a 75:25 lactide:glycolide ratio was attributed to

its slower degradation rate. Finally, the sustained release of Ab from the developed MS and the preservation of its activity was confirmed in vivo in a pharmacokinetic (pK) study realized in

rats. In conclusion, the application of the concept of entrapment into a polymer matrix for

stabilization and sustained release of biological compounds was demonstrated through this work.

RÉSUMÉ

Ce projet a pour but de développer un système de délivrance de médicament capable d’augmenter la stabilité et le temps de résidence in vivo des anticorps. Ce système sera administré par voie sous-cutanée et permettra un control précis de la libération du produit et de son niveau plasmatique. Cette plateforme technologique nous permettra de réduire la fréquence d’injection, de réduire potentiellement les effets secondaires et de maintenir des concentrations élevées en anticorps tout en améliorant la vie des patients atteints de maladies chroniques autoimmunes ou inflammatoires. Les formulations à base de polymères synthétiques, biodégradables (PLGA) ont été sélectionnés comme véhicules pour encapsuler les anticorps. Ils offrent en effet une bonne protection pour les anticorps and permettent une libération contrôlée de ceux-ci pendant une période définie. Après l’évaluation de différents méthodes d’encapsulation tels que les procédés d’eau-dans-huile-dans-eau (w/o/w) et solide-dans-huile-dans-eau (s/o/w), l’encapsulation des anticorps sous forme solide apparaissait plus apporpriée pour produire des microsphères de polymère chargées en anticorps. Cette technique nous permettait de maintenir l’anticorps sous sa forme monomérique et d’éviter la formation d’agrégats insolubles qui apparaissaient principalement à l’interface eau/huile. La première partie du projet a été d’optimiser à la fois la méthode nous permettant d’obtenir les anticorps sous forme de particules solides (spray-drying) et la méthode d’encapsulation de ces particules d’anticorps dans les microsphères de polymères. Cela a été réalisé par des plans d’expérience en utilisant une IgG bovine polyclonale comme molécule modèle. Durant l’optimisation du procédé de spray-drying,

les solutions aqueuses d’anticorps ont été atomisées en utilisant le mini Spray-Dryer assemblé avec une buse de pulvérisation d’un diamètre de 0.7 mm. En accord avec la taille particulaire (d(0.5) ~5 μm), la stabilité (absence de perte en monomère mesurée par chromatographie d’exclusion de taille et le rendement d’atomisation (> 60 % w/w), les paramètres d’atomisation ont été fixés: 3 mL/min pour le débit de liquide, 130°C /75°C pour la température d’entrée / température de sortie, 800 L/h pour le débit d’air d’atomisation et 30 m3/h pour le débit d’air de séchage. Pour le s/o/w, le dichlorométhane communément utilisé dans les procédés d’encapsulation a été remplacé par l’acétate d’éthyle qui est considéré comme un meilleure solvant organique en terme d’environnement et de sécurité. Les effets de plusieurs paramètres de fabrication ou de formulation ont été évalués sur les propriétés des microsphères polymériques d’anticorps (distribution de taille particulaire, taux de charge en anticorps, stabilité de l’anticorps et efficacité d’encapsulation). Plusieurs paramètres de fabrication et de formulation ont été statistiquement identifiés comme critiques pour obtenir un procédé reproductible (par exemple. La concentration en PLGA, le volume de phase externe, la vitesse d’émulsification et la quantité d’anticorps). La méthode d’encapsulation ainsi optimisée permettait d’obtenir un taux

de charge jusqu’à 6% (w/w) avec une efficacité d’encapsulation jusqu’à 60 % (w/w) tout en

préservant l’intégrité de l’anticorps encapsulé. Les microsphères produites étaient caractérisées

par un d(0.9) inférieur à 110 μm et montraient une libération après 24 h inférieure à 50 % (w/w).

Dans le seconde partie du projet, les procédés d’atomisation et d’encapsulation développés avec

l’IgG ont été appliqués à un anticorps monoclonal anti-TNF alpha humanisé pour confirmer la

conservation de l’activité de l’anticorps pendant ces procédés. La méthode s/o/w sélectionnée

permettait de produire des microsphères de PLGA chargées en anticorps avec un profil de libération jusqu’à 6 semaines et un maintien de la stabilité de l’actif. Afin de maintenir l’activité de l’anticorps, à la fois pendant le procédé d’encapsulation et pendant la libération, l’ajout d’un stabilisant tel que le tréhalose est apparu crucial ainsi que le choix du type de PLGA. Il a été démontré que l’utilisation du PLGA caractérisé par un ratio lactide :glycolide de 75 :25 (par exemple, Resomer ® RG755S) diminuait la formation d’espèces de faible poids moléculaire

pendant la dissolution. Cela contribuait à préserver l’activité de l’anticorps durant la libération à partir des microsphères. De plus, le profil de libération était modulé en fonction du type de polymère et de sa concentration. Par exemple, l’utilisation d’une solution à 10 % w/v RG755S conduisait à la production de microsphères d’anticorps avec un temps de libération sur 6

semaines. L’optimisation de la formulation et du procédé d’encapsulation a permis de produire

des microsphères avec des taux de charge en anticorps de maximum 13 % w/w. Il a été démontré

que ces microsphères, stockées à 5°C, étaient stables jusqu’à 12 semaines et que la sélection du

type de PLGA était critique pour assurer la stabilité du système. La meilleure stabilité a été

obtenue en utilisant le PLGA caractérisé par un ratio lactide :glycolide de 75 :25. Cela a été

attribué à sa plus faible vitesse de dégradation. Enfin, la libération contrôlée de l’anticorps à

partir de ces microsphères et la conservation de son activité ont été confirmées in vivo lors d’une

étude pharmacocinétique réalisée chez le rat. En conclusion, ce travail a permis de démontrer

l’application du concept d’ « emprisonnement » des composés biologiques dans des matrices

polymériques afin de les stabiliser et contrôler leur libération.
Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished

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Carlier, Emeric. "Development of 3D printed implants for subcutaneous administration of sustained-release antibodies." Doctoral thesis, Universite Libre de Bruxelles, 2021. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/326756.

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Thèse réalisée dans le cadre d'une collaboration avec UCB Pharma et la région Wallonne s'inscrivant dans le cadre du projet SAS. Le but de ce projet était de développer des implants sous-cutanés imprimés en trois dimensions pour permettre une libération d’anticorps thérapeutique de manière prolongée au cours du temps. En effet, les thérapies disponibles sont souvent administrées par voie intraveineuse, ce qui peut réduire la compliance des patients dû à l’inconfort et à la fréquence de ces administrations. Les systèmes de délivrance, tels que des implants, peuvent limiter les fréquences d’administration grâce à l’insertion d’un dispositif qui libèrera le principe actif au cours du temps durant une période donnée. Les implants s’inscrivent comme une alternative aux microsphères qui sont également des dispositifs développés et investigués en vue de favoriser l’adhésion et la compliance des patients. L’avènement du 3D dans le milieu pharmaceutique a montré une certaine frénésie liée au développement de la médecine personnalisée et à l’innovation du procédé dans ce secteur. La sélection d’un matériau biocompatible et biorésorbable tel que le PLGA représente une véritable plus-value dans le développement d’implant. Etant donné que ces implants sont biodégradables, le retrait n’est pas à envisager, ce qui limite les désagréments du patient à un seul acte chirurgical lors de l’implantation. Au cours de ce travail, une approche pragmatique a d’abord été abordée sur les procédés d’extrusion à chaud et de l’impression 3D en utilisant un polymère couramment employé dans l’impression grand public, le PLA. L’investigation des paramètres d’impressions (température d’impression, epaisseur de couche et vitesse d’impression) et l’usage de divers plastifiants (la triacétine (TA), le polyethylène glycol 400 (PEG 400), le citrate de triéthyle (TEC) et l’acétyle citrate de triéthyle (ATEC)) pour faciliter les procédés à chaud et dans l’idée de réduire les températures d’extrusion et d’impression du matériau ont été évalués. Ces essais ont démontré l’effet de la température d’impression sur la qualité de l’impression et principalement sur les propriétés du matériau comme la force de traction et la ductilité. De plus, l’ajout de plastifiant à la matrice du PLA a permis de diminuer sa température de transition vitreuse. Par exemple, la température de transition vitreuse du PLA a été diminuée de 53 °C à 34 °C par l’ajout de PEG 400. Cette approche avait pour but d’évaluer la possibilité de diminuer les températures d’impression dans l’optique d’encapsuler à chaud un anticorps sensible à la chaleur pour la suite de ce travail.Ensuite, le développement de filaments imprimables contenant des anticorps a été abordé et mis en place à l’aide d’un modèle d’anticorps polyclonal disponible en grandes quantités et à des coûts relativement faibles. Un anticorps à l’état solide a été favorisé dans le procédé car il est largement accepté que les protéines sous forme solide sont plus stables au cours du temps en comparaison aux solutions d’anticorps. De plus, cet état solide facilite les manipulations précédant l’extrusion comme l’étape de mélange. Pour la réalisation des filaments, différents types de PLGA ont été investigués afin d’atteindre les propriétés nécessaires à l’impression en termes de diamètre mais également de comportement physique. Ces dérivés étaient caractérisés par des masses moléculaires différentes comme pour le PDLG5004 (44 kDa), le RG502 (7-17 kDa) et parmis eux, un copolymère PEG-PLGA (2 kDa-20 kDa). Un PLGA de faible masse moléculaire a été sélectionné pour développer ce filament. En effet, les extrusions étaient réalisables à une température maximum de 90 °C et les impressions à 113 °C minimum. L’un des enjeux cruciaux du développement de filament imprimable contenant un anticorps à haute concentration, au minimum 15% (w/w), était d’en assurer l’homogénéité. Cependant, l’usage de températures aussi élevées lors de l’impression a induit la dégradation de l’anticorps par la formation d’agrégats et principalement de fragments. Ces derniers sont généralement produits lors de procédé à haute température ou par l’usage de conditions drastiques telles que l’acidification du milieu. Cette plateforme a été adaptée à l’encapsulation d’anticorps thérapeutique fournit par UCB Pharma. L’usage d’un anticorps monoclonal possédant une stabilité supérieure à celle du modèle initialement utilisé permettrait d’identifier l’impact du procédé sur l’intégrité de l’anticorps. La formulation de l’anticorps a été réalisée en utilisant différents stabilisants conventionnels (sucrose (Suc), trehalose (Tre), 2-Hydroxypropyl-beta-cyclodextrine (HP-β-CD), inuline (Inu) et sorbitol (Sor)) et reconnus pour la stabilisation des protéines. A côté des excipients ajoutés, différentes quantités d’excipients ont été investigués. Ces manipulations ont montré que la stabilité de l’anticorps était privilégiée à l’aide du sucrose et du tréhalose à un ratio anticorps monoclonal:excipient de 2.0:1. En gardant ce ratio, l’ajout d’un acide aminé (leucine) aux deux disaccharides précédemment cités, a amélioré la stabilité de l’anticorps vis-à-vis des procédés à chaud (extrusion et impression 3D). L’homogénéité au sein des filaments imprimables et des pièces 3D a été confirmée tout au long du procédé. En effet, les charges en anticorps étaient similaires à la charge théorique de 15% (w/w). Aucune fragmentation de l’anticorps n’a été observée à l’issue des procédés à chaud. Cependant, une augmentation des agrégats de 2.6% en solution à 3.6% après impression 3D a été constatée à la fin du processus. Après avoir stabilisé l’anticorps, le but premier étant d’en promouvoir une libération prolongée au cours du temps. Les profils ont révélé une libération en trois phases au cours du temps mais avec un relargage après 24h relativement faible (< 5%) dû à la densité des matrices polymériques. Ensuite, la dégradation du polymère représente l’élément limitant la libération de l’anticorps au cours du temps. En effet, l’érosion du polymère joue un rôle clé dans la libération de l’anticorps encapsulé. La libération au cours du temps a été démontrée sur une période allant jusqu’à 15 semaines. La stabilité de l’anticorps dans le milieu de dissolution a été évaluée et une dégradation de celui-ci au cours du temps a été observée. Cette dégradation est principalement liée à l’érosion du polymère et à l’acidification du milieu au cours du test de dissolution. Après avoir optimisé la formulation de l’anticorps et avoir démontré la libération prolongée de celui-ci, son affinité restait à être étudiée. La capacité de l’anticorps à se lier à sa cible a pu être démontrée après 24h de dissolution mais cette affinité s’est réduite au cours de la durée de la dissolution avec une augmentation de l’agrégation et de la fragmentation de l’anticorps. Une étude de stabilité a également démontré que les implants imprimés en 3D sont stables à une température 5 °C sur une durée de 6 mois. Aucun élément de dégradation n’a été observé au cours du temps et l’affinité de l’anticorps a été préservée au cours de l’étude. Finalement, cette plateforme a également été évaluée pour l’encapsulation d’une troisième molécule biologique, un fragment d’anticorps monoclonal, pour d’une part en estimer la stabilité et l’applicabilité et d’autre part envisager une prochaine étude pré-clinique sur rongeurs. Le fragment d’anticorps a montré une stabilité supérieure à celle de l’anticorps monoclonal avec une faible agrégation après l’extrusion et l’impression. La libération prolongée du fragment a été évaluée sur 8 semaines et une libération du fragment de 79% a été observée avec une formulation contenant du tréhalose et de la leucine. En effet, les fragments d’anticorps ont une demi-vie plasmatique relativement faible, de l’ordre de 28 minutes, ce qui donne tout son sens à des systèmes à libération prolongée. Pour finir, la réalisation d’une étude pré-clinique permettrait de valider le modèle. En conclusion, ce travail a démontré la faisabilité de l’usage de l’impression 3D en vue de développer des systèmes à libération prolongée contenant des anticorps et en utilisant des procédés à hautes températures. Ces implants ont été caractérisés par une stabilité favorable et une libération intéressante qui feront l’objet d’investigation lors d’études pharmacocinétiques.
Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie)
info:eu-repo/semantics/nonPublished
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Edwards, Eric. "DEVELOPMENT OF A NOVEL APPROACH TO ASSESS QUALITATIVE AND QUANTITATIVE DYNAMICS ASSOCIATED WITH THE SUBCUTANEOUS OR INTRAMUSCULAR ADMINISTRATION OF PHARMACEUTICALS AND ASSOCIATED PARENTERAL DELIVERY SYSTEMS." VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/279.

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There has been a significant increase in the number of injectable pharmaceutical products over the last decade that have been incorporated into unique delivery systems such as pen injectors, auto-injectors, or pre-filled syringes. The advancement of these delivery systems and the paradigm shift towards administration of injectables in the out-of-hospital or home setting have introduced variables that can affect the bioavailability of injectable drugs and potential pharmacologic outcomes. An approach that allows for the qualitative and quantitative dispersion assessment of an injectable at the moment of tissue deposition coupled with an assessment of systemic exposure parameters could provide substantial information to researchers developing new injectable formulations and associated delivery systems. The overall goal of this research project was to develop an approach for investigating various injection dynamics, more specifically, dispersion dynamics associated with the administration of parenteral pharmaceutical products utilizing delivery technologies designed to deliver drug below the dermis. This was accomplished by first evaluating the safety and usability of computed tomography (CT) scanning as a novel radioimaging approach to assess qualitative and quantitative dispersion parameters in a cadaver study followed by a randomized, controlled, clinical study to assess CT tissue dispersion and the systemic exposure of iohexol, administered subcutaneously by two delivery systems in human volunteers. The primary finding of this work was the demonstration that CT scanning may be combined with a systemic exposure assessment to provide an effective paradigm for investigating dynamics of injectable delivery impacted by a variety of factors, including the choice of delivery system. In this study, iohexol delivered subcutaneously by an auto-injector resulted in notable qualitative and quantitative dispersion differences, including a higher rate of iohexol loss from the extravascular tissue, as well as differences in early plasma exposure as compared to a pre-filled syringe delivery system. The injections and CT scanning were well tolerated with adverse events limited to mild injection site reactions resolving without intervention. This research resulted in a novel local in-vivo(extravascular disappearance), systemic in-vivo(intravascular appearance) correlation approach that could be utilized to assess a wide variety of dynamics associated with injectable drug delivery below the dermis.
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Zhi, Kaining. "Formulation and Fabrication of a Novel Subcutaneous Implant for the Zero-Order Release of Selected Protein and Small Molecule Drugs." Diss., Temple University Libraries, 2017. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/482373.

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Pharmaceutical Sciences
Ph.D.
Diabetes is a leading cause of death and disability in the United States. Diabetes requires a lifetime medical treatment. Some diabetes drugs could be taken orally, while others require daily injection or inhalation to maximize bioavailability and minimize toxicity. Parenteral delivery is a group of delivery routes which bypass human gastrointestinal track. Among all the parenteral methods, we chose subcutaneous implant based on its fast act and high patient compliance. When using subcutaneous implant, drug release needs to be strictly controlled. There are three major groups of controlled release methods. Solvent controlled system is already used as osmotic implant. Matrix controlled system is used in Zoladex® implant to treat cancer. Membrane controlled systems is widely used in coating tablets, but not that popular as an implant. Based on the research reported by previous scientists, we decided to build a hybrid system using both matrix and membrane control to delivery human insulin and other small molecule drugs. Subcutaneous environment is different from human GI track. It has less tolerance for external materials so many polymers cannot be used. From the FDA safe excipient database, we selected albumin as our primary polymer and gelatin as secondary choice. In our preliminary insulin diffusion study, we successfully found that insulin mixed with albumin provided a slower diffusion rate compared with control. In addition, we added zinc chloride, a metal salt that can precipitate albumin. The insulin diffusion rate is further reduced. The preliminary study proved that matrix control using albumin is definitely feasible and we might add zinc chloride as another factor. In order to fabricate an implant with appropriate size, we use lyophilisation technology to produce uniformly mixed matrix. Apart from albumin and human insulin, we added sucrose as protectant and plasticizer. The fine powder after freeze-dry was pressed as a form of tablet. The tablets were sealed in Falcon® cell culture insert. Cell culture insert provide a cylinder shape and 0.3 cm2 surface area for drug release. Insulin release study provided a zero order kinetics from prototypes with zinc chloride or 0.4 micron pore size membrane. Caffeine was used as a model drug to investigate the releasing mechanism. Three pore size membranes (0.4, 3 and 8 micron) were tested with same formulation. While 0.4 micron prototypes provided the slowest release, 3 micron ones surprisingly released caffeine faster than 8 micron implants. We calculated the porosity with pore size and concluded that the percentage of open area on a membrane is the key point to control caffeine release. 0.4 micron membranes were used for future research. We increased the percentage of albumin in our excipient, and achieved a slower caffeine release. However, the zero order release could only last for 3 days. After we replaced sucrose with gelatin, a 5 day zero order release of caffeine was achieved. With all the results, we proposed our “Three Phase” drug release mechanism controlled by both membrane and matrix. Seven other small molecule drugs were tested using our prototype. Cloudy suspension was observed with slightly soluble drugs. We updated our “Three Phase” drug release mechanism with the influence of drug solubility. Data shows that releasing rate with same formulation and membrane follows the solubility in pH 7.4. This result proves that our prototype might be used for different drugs based on their solubility. Finally, with all the information of our prototype, we decided to build a “smart insulin implant” with dose adjustment. We proposed an electrical controlled implant with different porosity membranes. Solenoid was used as the mechanical arm to control membrane porosity. 3-D printing technology was used to produce the first real prototype of our implant. Finally, insulin implant with clinically effective insulin release rate was achieved.
Temple University--Theses
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Mohangi, Govindrau Udaibhan. "Comparative study of heterotopic bone induction using porcine bone morphogenetic proteins delivered into the rodent subcutaneous space with allogeneic and xenogeneic collagen carriers." Diss., 2009. http://hdl.handle.net/2263/25476.

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Books on the topic "Subcutaneous delivery"

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Sylvestervich, Andrea. A manual for subcutaneous infusion pumps at Kingston General Hospital and Kingston Regional Cancer Centre. [Kingston, Ont.]: Kingston General Hospital, 1990.

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Kang, David W., and Renee Tannenbaum. ENHANZE® Drug Delivery Technology: Advancing Subcutaneous Drug Delivery Using Recombinant Human Hyaluronidase PH20. Karger AG, S., 2022.

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Kang, David W., and Renee Tannenbaum. ENHANZE® Drug Delivery Technology: Advancing Subcutaneous Drug Delivery Using Recombinant Human Hyaluronidase PH20. Karger AG, S., 2022.

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Book chapters on the topic "Subcutaneous delivery"

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Scioli Montoto, Sebastian, and Maria Esperanza Ruiz. "Subcutaneous Drug Delivery." In The ADME Encyclopedia, 1107–14. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-84860-6_100.

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Scioli Montoto, Sebastian, and Maria Esperanza Ruiz. "Subcutaneous Drug Delivery." In The ADME Encyclopedia, 1–8. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-51519-5_100-1.

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Hovorka, Roman. "Closing the loop." In Oxford Textbook of Endocrinology and Diabetes, 1869–74. Oxford University Press, 2011. http://dx.doi.org/10.1093/med/9780199235292.003.1455.

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The standard therapy of type 1 diabetes is based on multiple daily injections of short- and long acting-insulin analogues accompanied by blood glucose self-monitoring. However, treatment goals identified by the Diabetes Control and Complications Trial are difficult to achieve due, at least in part, to a high risk of hypoglycaemia associated with many currents forms of intensive insulin therapy. Recent technological developments in real-time subcutaneous continuous glucose monitoring (CGM), combined with the continuous subcutaneous insulin infusion (CSII), could potentially reduce this risk. Since late 1990s at least five continuous or semicontinuous glucose monitors have received regulatory approval (1). CGM has been shown to improve glycaemic control in adults with type 1 diabetes, although apparent barriers to effectiveness in children and adolescents remain to be identified (see Chapter 13.4.9.1) (2). The availability of commercial CGM devices has reinvigorated research towards closed-loop systems (3-6), in which insulin is delivered according to real-time needs, as opposed to open-loop systems, which lack real-time responsiveness to changing glucose concentrations. Closed-loop insulin delivery, in which the insulin delivery is informed by the measured glucose concentrations has the potential gradually to revolutionize the management of type 1 diabetes by reducing or eliminating the risk of hypoglycaemia while achieving near-normal glucose levels. A closed-loop system, also called the ‘artificial pancreas’, comprises three components: a CGM device to measure real-time glucose concentration, a titrating algorithm to compute the amount of insulin needed, and an insulin pump delivering a rapid-acting insulin analogue (see Fig. 13.4.9.2.1). Only a few prototypes have been developed. Progress has been hindered by suboptimal accuracy and reliability of CGM devices, the relatively slow absorption of subcutaneously administered ‘rapid’-acting insulin analogues, and the lack of adequate control algorithms. So far, testing has been confined to the clinical setting. However, a concentrated effort promises an accelerated progress towards home testing of closed-loop systems. The research focus centres on systems utilizing subcutaneous glucose sensing and subcutaneous insulin delivery. This approach has the greatest potential for a near-future commercial exploitation, although other approaches utilizing intraperitoneal or intravenous sensing/delivery are, in principle, also feasible.
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Bittner, Beate, and Johannes Schmidt. "Subcutaneous drug delivery devices—Enablers of a flexible care setting." In Drug Delivery Devices and Therapeutic Systems, 159–79. Elsevier, 2021. http://dx.doi.org/10.1016/b978-0-12-819838-4.00021-3.

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Hovorka, Roman, and Charlotte Boughton. "“Closed Loop” Insulin Delivery." In Oxford Textbook of Endocrinology and Diabetes 3e, edited by John A. H. Wass, Wiebke Arlt, and Robert K. Semple, 2071–76. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780198870197.003.0264.

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Glycaemic control with insulin therapy is influenced by multiple factors, contributing to the notable variability in insulin requirements and making self-management of type 1 diabetes (T1D) challenging. As a result, the majority of people with T1D are unable to achieve their recommended therapeutic goals. Rapid progress has been made over the past decade with the development of a closed-loop insulin delivery system, also known as the ‘artificial pancreas’ which emulates the glucose-responsive functionality of the pancreatic beta cell. A control algorithm autonomously and continually increases and decreases subcutaneous insulin delivery based on real-time sensor glucose levels to achieve normoglycaemia while mitigating hyper- and hypoglycaemia. Randomized clinical studies in outpatient and home settings have demonstrated improved glycaemic outcomes, reduced risk of hypoglycaemia, and positive user attitudes. The Food and Drug Administration (FDA) approval of the first hybrid closed-loop system in 2017 marks a new era in the management of T1D using diabetes technology.
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Saltzman, W. Mark. "Controlled Drug Delivery Systems." In Drug Delivery. Oxford University Press, 2001. http://dx.doi.org/10.1093/oso/9780195085891.003.0015.

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In most forms of drug delivery, spatial localization and duration of drug concentration are constrained by organ physiology and metabolism. For example, drugs administered orally will distribute to tissues based on the principles of diffusion, permeation, and flow presented in Part II of this book. If the duration of therapy provided by a single administration is insufficient, the drug must be readministered. Localization of drug can be controlled by injection, but only within limited spatial constraints, and effectiveness after an injection is usually short-lived. Controlled-delivery systems offer an alternative approach to regulating both the duration and spatial localization of therapeutic agents. In controlled delivery, the active agent is combined with other (usually synthetic) components to produce a delivery system. Unlike drug modification, which results in new agents that are single molecules, or assemblies of a limited number of molecules, drug delivery systems are usually macroscopic. Like drug modification, controlled-delivery systems frequently involve combinations of active agents with inert polymeric materials. In this text, controlled-delivery systems are distinguished from “sustained-release” drug formulations. Sustained release is often achieved by mixing an active agent with excipients or binders that alter the agent’s rate of dissolution in the intestinal tract or adsorption from a local injection site. The distinction between sustained release (often achieved by drug formulation) and controlled delivery or controlled release is somewhat arbitrary. In our definition, controlled delivery systems must (1) include a component that can be engineered to regulate an essential characteristic (e.g., duration of release, rate of release, or targeting) and (2) have a duration of action longer than a day. Many polymeric materials are available for the development of drug delivery systems (see Appendix A). Non-degradable, hydrophobic polymers have been used the most extensively. Reservoir drug delivery devices, in which a liquid reservoir of drug is enclosed in a silicone elastomer tube, were first demonstrated to provide controlled release of small molecules several decades ago [1]. This discovery eventually led to clinically useful devices, including the Norplant® (Wyeth-Ayerst Laboratories) contraceptive delivery system, which provides reliable delivery of levonorgestrel for 5 years following subcutaneous implantation.
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Sahu, Anil Kumar, Vishal Jain, Gyanil Kumar Sahu, Saraswati Prasad Mishra, Koushlesh Mishra, Vaibhav Tripathi, Shweta Dutta, and Pankaj Kashyap. "Recent Advancement to Improve Intestinal Absorption of Macromolecular Drugs." In Advancements in Controlled Drug Delivery Systems, 237–56. IGI Global, 2022. http://dx.doi.org/10.4018/978-1-7998-8908-3.ch010.

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Therapy of many ailments such as malignancy hepatitis, AIDS, cardiovascular diseases are carried out by using biological macromolecular drugs such as fusion protein drugs and antibodies. The majority of macromolecular drugs are either proteins or peptides, which are made into solution or suspension and are administered through intravenous or subcutaneous route that are invasive and painful. A significant level of attention has been given to oral macromolecular drug delivery over the last 30 years. The major obstruction faced by macromolecular drugs administered through oral route is the physical and biochemical properties of the epithelial layer of the gastrointestinal tract, which acts as a boundary. The chapter focuses on the physiological hindrance faced by protein and peptide during their conveyance through the GIT. Moreover, discussion about techniques that are used for dodging the boundaries and for enhancing the penetration of drug through GIT have been done. These methodologies can be of great value for absorption of drugs like bio macromolecules through the intestines.
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Crepeau, Amy Z. "Neuropharmacology." In Mayo Clinic Neurology Board Review, edited by Kelly D. Flemming, 215–24. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780197512166.003.0027.

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Medications used in the treatment of nervous system disorders typically modulate neurotransmitter function or action potential propagation and alter neurologic function. This chapter reviews the principles of pharmacokinetics, the major targets for drug action to provide a basis for understanding how medications exert their action, and disease-specific treatments. An understanding of the pharmacokinetic principles of neurologic medications is important for prescribing and ordering medication. Multiple routes of administration, including intravenous, sublingual, intramuscular, subcutaneous, rectal, oral, and transdermal, are available for delivery of neurologic medications.
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Burnette, Michelle S., Laura Roland, Everett Chu, and Marianne David. "Alternative Regional Anesthetic Techniques." In Obstetric Anesthesia Practice, 174–85. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780190099824.003.0014.

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When neuraxial blocks are contraindicated in parturients desiring labor analgesia or requiring postoperative pain control after a cesarean delivery, alternate regional techniques can be considered. This chapter discusses the techniques available to the clinician to provide relief during the first and second stages of labor. These include paracervical block, pudendal block, and perineal infiltration. The chapter also discusses regional techniques to relieve postoperative pain after cesarean delivery. These include transversus abdominis plane (TAP) block, quadratus lumborum block (QLB), wound infiltration catheters, ilioinguinal-iliohypogastric (IIIH) block, and subcutaneous infiltration of local anesthetics. For each procedure, the technique is described, along with a discussion of the clinical indications and complications. Residents, advanced practitioners, and physicians practicing in the field of anesthesiology, family medicine, and obstetrics will benefit from this chapter.
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Pickup, John, and Nick Oliver. "Glucose Monitoring and Sensing." In Oxford Textbook of Endocrinology and Diabetes 3e, edited by John A. H. Wass, Wiebke Arlt, and Robert K. Semple, 1975–78. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780198870197.003.0251.

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Glucose monitoring is critical to enable people with diabetes to self-manage effectively, especially those with insulin-treated diabetes. Self-monitoring of capillary blood glucose (SMBG) has been available to people with diabetes for four decades and is now being supplemented and, for some, superseded by continuous glucose monitoring (CGM) provided by subcutaneously implanted sensors. Information such as estimated glucose concentrations, rate of change, alerts for impending glucose extremes and historical patterns can enable more appropriate carbohydrate intake, physical activity, insulin administration, and lifestyle decisions in real-time. Improvements in overall glycaemic control, as measured by HbA1c, time-in-range for glucose readings, hypoglycaemia exposure, and hypoglycaemic events, as well as quality of life, have all been reported with CGM. Flash glucose monitoring (FGM) with retrospective review of previously recorded continuous glucose readings from a subcutaneous glucose sensor is likely to be a replacement for SMBG. Sensor-augmented insulin pump therapy uses CGM data for feedback control of insulin delivery, and pumps with automatic low glucose-activated suspend of the basal insulin infusion are already in widespread clinical use and effective at reducing hypoglycaemia in type 1 diabetes. Hybrid closed-loop systems employing CGM are entering practice and fully closed-loop systems are under development.
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Conference papers on the topic "Subcutaneous delivery"

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Jones, Richard W., and Francesco Gianni. "Subcutaneous versus intra-peritoneal insulin delivery in the artificial pancreas." In 2018 13th IEEE Conference on Industrial Electronics and Applications (ICIEA). IEEE, 2018. http://dx.doi.org/10.1109/iciea.2018.8397770.

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Park, Eun-Joo, Jeff Dodds, Nadine Barrie Smith, Kullervo Hynynen, and Jacques Souquet. "Dose comparison of ultrasonic transdermal insulin delivery to subcutaneous insulin injection." In 9TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC ULTRASOUND: ISTU—2009. AIP, 2010. http://dx.doi.org/10.1063/1.3367167.

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Dungel, Paul, Yvonne Moussy, and Lawrence Hersh. "Two Methods of Determining [3H]Dexamethasone Distribution in Rat Subcutaneous Tissue." In ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-172803.

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Several recent reports suggest that controlled local release of dexamethasone may be useful for preventing inflammation around an implantable glucose sensor [1,2]. This decrease in inflammation is expected to increase glucose sensor function and lifetime. Local delivery of dexamethasone would permit high interstitial drug concentrations at the site of glucose sensor implantation without producing high systemic drug levels. Although dexamethasone is a commonly used anti-inflammatory agent, its local concentration, diffusion coefficient and rate of elimination have not been reported following subcutaneous release. The ability of dexamethasone to penetrate subcutaneous tissue can be measured and quantified by comparison to mathematical models [3]. This method allows a reliable estimate of the drug concentration in the tissue near the implanted glucose sensor.
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Shi, Jing, Pouyan Mohajerani, Stefan Morscher, Wouter Driessen, Neal Burton, Daniel Razansky, and Vasilis Ntziachristos. "Abstract 58: Comparative determination of compound delivery to orthotopic and subcutaneous tumors by non-invasive imaging." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-58.

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Chaudhuri, Buddhadev P., F. Ceyssens, S. Celen, G. Bormans, M. Kraft, and R. Puers. "In-vivo Intradermal Delivery of Co-57 labeled Vitamin B-12, and Subsequent Comparison with Standard Subcutaneous Administration *." In 2019 41st Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC). IEEE, 2019. http://dx.doi.org/10.1109/embc.2019.8857543.

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Wang, Bin, Hui Hu, Ayodeji Demuren, and Eric Gyurcsko. "Experimental and Theoretical Studies of Pulsed Micro Flows Pertinent to Continuous Subcutaneous Insulin Infusion (CSII) Therapy." In ASME 2010 3rd Joint US-European Fluids Engineering Summer Meeting collocated with 8th International Conference on Nanochannels, Microchannels, and Minichannels. ASMEDC, 2010. http://dx.doi.org/10.1115/fedsm-icnmm2010-30303.

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Continuous subcutaneous insulin infusion (CSII) therapy, also known as insulin pump therapy, has become an important advancement in diabetes therapy to improve the quality of life for millions of diabetes patients. Insulin delivery failures caused by the precipitations of insulin within micro-sized CSII tubing systems have been reported in recent years. It has also been conjectured that the flow of insulin through an insulin infusion set may be reduced or inhibited by air bubbles entrained into the capillary CSII tubing system during the typical three- to five-day operation between refills. Currently, most solutions to insulin occlusion related problems are based on clinical trials. In the present study, an experimental and theoretic study was conducted to investigate the pulsed flows inside the micro-sized CSII tubing system. A micro-PIV system was used to provide detailed flow velocity field measurements inside the capillary CSII tubing system to characterize the transient behavior of the micro-flows upon the pulsed actuation of the insulin pump used in CSII therapy. It was found that the microflow inside the CSII tubing system is highly unsteady, which is much more interesting than the creeping flow that the nominal averaged flow rates would suggest. A theoretic frame work was also performed to model the pulsed micro-flows driven by the insulin pump to predict the transient behavior of the microflows and velocity distributions inside the micro-sized CSII tubing system. The measurement results and the theoretic predictions were compared quantitatively to elucidate underlying physics for a better understanding of the microphysical process associated with the insulin delivery in order to provide a better guidance for troubleshooting of insulin occlusion in CSII therapy.
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Worley, Deanna R., Ryan J. Hansen, Laura S. Chubb, and Daniel L. Gustafson. "Abstract B48: Subcutaneous delivery of docetaxel and carboplatin accumulate preferentially in lymphatic circulation as compared to intravenous delivery in rats with surgically created lymph and venous fistulae." In Abstracts: AACR Special Conference: The Translational Impact of Model Organisms in Cancer; November 5-8, 2013; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1557-3125.modorg-b48.

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Zedelmair, Michael M., and Abhijit Mukherjee. "Numerical Simulation of Insulin Depot Formation in Subcutaneous Tissue Comparing Different Cannula Geometries." In ASME 2016 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2016. http://dx.doi.org/10.1115/imece2016-67473.

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In this study, the impact of the cannula geometry on the formation of the depot in subcutaneous tissue is investigated when injecting insulin using an insulin pump. The simulations have been conducted using the Computational Fluid Dynamics (CFD) software ANSYS Fluent. The study is focusing on rapid acting insulin analogues typically used in insulin pump therapy, which enter the bloodstream very shortly after administration. A previously developed 2-dimensional simulation has been transferred into a 3-dimensional case in order to simulate cases with non-axisymmetric geometries. The tissue has been modeled as a homogeneous anisotropic porous media by the use of different porosity values in the parallel and perpendicular direction with respect to the skin surface. The process of absorption is implemented into the model by the use of a locally variable species sink term. The basic case, simulated with a solid cannula, has been compared to other cannula geometries in order to evaluate if the delivery of insulin in the tissue can be improved. The geometries under consideration are the addition of circumferential holes in the wall of the cannula as well as using an array of cannulas instead of a single cannula. The depot formation is analyzed simulating a standard bolus injection of 0.05ml of insulin using an injection time of 25 seconds. It is observed that the addition of multiple holes in the wall of the cannula or using an array of cannulas can alter the shape of the depot quite significantly. The impact of the depot shape on the diffusion of insulin in the tissue has been evaluated by measuring the total volume of the depot after injection.
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BUXTON, DE, BJ CHILDERS, and KC OBERG. "A NOVEL METHOD TO ENHANCE THE SUBCUTANEOUS DETECTION OF BIOLUMINESCENCE IN THE FACULTATIVE ANAEROBE, STREPTOCOCCUS PYOGENES, BY DMSO-ASSISTED TRANSDERMAL OXYGEN DELIVERY." In Proceedings of the 13th International Symposium. WORLD SCIENTIFIC, 2005. http://dx.doi.org/10.1142/9789812702203_0088.

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Meschengieser, S. S., A. I. Woods, and M. Z. Lazzari. "ANTICOAGULATION IN PREGNANCY IN PATIENTS WITH CARDIAC VALVE PROSTHESIS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643266.

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The use of oral anticoagulation in pregnancy is controversial due to the risk of embryopathy (1° trimester), intracerebral hemorrhages (2° trimester) and the use of heparin is associated with a high morbidity due to abortion and prematurity. The outcome of 50 pregnancies in 30 patients with heart prosthesis was evaluated. Acenocoumarol and aspirin 500 mg/daily were given in all the patients since their surgery. Anticoagulant doses were controlled with prothrombin time (PT) performed with human brain thromboplastin and APTT. The therapeutic range for the PT was the International Calibrated Ratio (ICR) 2.5 to 3.5. In 12 pregnancies, oral anticoagulation was replaced by subcutaneous heparin in the first trimester; the same policy was followed before delivery except in 4 cases. The foetal loss was 34% with equal distribution along the three trimesters and no correlation with excess of anticoagulation. The incidence of hemorrhage was 6% and the rate of cerebral embolism was also 6% (3 on to 50). Two of the three episodes of embolism appeared while patients were on heparin. A total of 33 normal babies were born (66%). No typical warfarin embryopathy was found and no perinatal mortality was observed. A slight reduction in the anticoagulant doses was necessary in almost half of the cases.As the rate of foetal loss with heparin is not better than with oral anticoagulants and the incidence of embolism is higher, we are doubtful about the indication of subcutaneous heparin in the first trimester considering our absence of malformations with the acenocoumarin.
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Reports on the topic "Subcutaneous delivery"

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Expanding access and method choice: Evidence of client self-administration of injectables and private sector provision of family planning services in three West African countries. Population Council, 2020. http://dx.doi.org/10.31899/sbsr2020.1003.

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Governments across West Africa have expressed their commitment to increasing access to voluntary family planning (FP) through global and regional initiatives such as FP2020 and the Ouagadougou Partnership, and through targeted national strategies. Ghana, Nigeria and Senegal, among other countries, have been exploring new strategies to expand access to voluntary FP service delivery. Context-specific evidence was needed for two promising strategies—1) task sharing of FP services to private sector drug shops and pharmacies, and 2) introducing self-injection of subcutaneous depot medroxyprogesterone acetate (DMPA-SC). The Evidence Project collaborated with stakeholders in Ghana, Nigeria, and Senegal to use implementation science (IS) to expand the evidence base on these promising approaches. In this brief, we describe key study results from the three countries and how results have been used to increase access to voluntary family planning and expand method choice.
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