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Literatura académica sobre el tema "Drug-Polymer conjugates"

Autor: Grafiati

Publicado: 25 de mayo de 2024

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Artículos de revistas sobre el tema "Drug-Polymer conjugates"

Libánská, Alena, Eva Randárová, Franck Lager, Gilles Renault, Daniel Scherman y Tomáš Etrych. "Polymer Nanomedicines with Ph-Sensitive Release of Dexamethasone for the Localized Treatment of Inflammation". Pharmaceutics 12, n.º 8 (25 de julio de 2020): 700. http://dx.doi.org/10.3390/pharmaceutics12080700.

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Polymer-drug conjugates have several advantages in controlled drug delivery to inflammation as they can accumulate and release the drug in inflamed tissues or cells, which could circumvent the shortcomings of current therapy. To improve the therapeutic potential of polymer-drug conjugates in joint inflammation, we synthesized polymer conjugates based on N-(2-hydroxypropyl) methacrylamide) copolymers labeled with a near-infrared fluorescent dye and covalently linked to the anti-inflammatory drug dexamethasone (DEX). The drug was bound to the polymer via a spacer enabling pH-sensitive drug release in conditions mimicking the environment inside inflammation-related cells. An in vivo murine model of adjuvant-induced arthritis was used to confirm the accumulation of polymer conjugates in arthritic joints, which occurred rapidly after conjugate application and remained until the end of the experiment. Several tested dosage schemes of polymer DEX-OPB conjugate showed superior anti-inflammatory efficacy. The highest therapeutic effect was obtained by repeated i.p. application of polymer conjugate (3 × 1 mg/kg of DEX eq.), which led to a reduction in the severity of inflammation in the ankle by more than 90%, compared to 40% in mice treated with free DEX.

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Duncan, Ruth. "Drug-polymer conjugates". Anti-Cancer Drugs 3, n.º 3 (junio de 1992): 175–210. http://dx.doi.org/10.1097/00001813-199206000-00001.

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Duncan, R. "Designing polymer conjugates as lysosomotropic nanomedicines". Biochemical Society Transactions 35, n.º 1 (22 de enero de 2007): 56–60. http://dx.doi.org/10.1042/bst0350056.

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Marriage of cell biology (the concept of ‘lysosomotropic drug delivery’) and the realization that water-soluble synthetic polymers might provide an ideal platform for targeted drug delivery led to the first synthetic polymer–drug conjugates that entered clinical trials as anticancer agents. Conceptually, polymer conjugates share many features with other macromolecular drugs, but they have the added advantage of the versatility of synthetic chemistry that allows tailoring of molecular mass and addition of biomimetic features. Conjugate characteristics must be optimized carefully to ensure that the polymeric carrier is biocompatible and that the polymer molecular mass enables tumour-selective targeting followed by endocytic internalization. The polymer–drug linker must be stable in transit, but be degraded at an optimal rate intracellularly to liberate active drug. Our early studies designed two HPMA [N-(2-hydroxypropyl)methacrylamide] copolymer conjugates containing doxorubicin that became the first synthetic polymer–drug conjugates to be tested in phase I/II clinical trials. Since, a further four HPMA copolymer–anticancer drug conjugates (most recently polymer platinates) and the first polymer-based γ-camera imaging agents followed. Polymer–drug linkers cleaved by lysosomal thiol-dependent proteases and the reduced pH of endosomes and lysosomes have been used widely to facilitate drug liberation. It is becoming clear that inappropriate trafficking and/or malfunction of enzymatic activation can lead to new mechanisms of clinical resistance. Recent studies have described HPMA copolymer conjugates carrying a combination of both endocrine and chemotherapy that are markedly more active than individual conjugates carrying a single drug. Moreover, current research is investigating novel dendritic polymer architectures and novel biodegradable polymers as drug carriers that will provide improved drug delivery and imaging probes in the future. The present paper reviews the clinical status of polymeric anticancer agents, the rationale for the design of polymer therapeutics and discusses the benefits and challenges of lysosomotropic delivery.

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Elvira, C., A. Gallardo, J. Roman y A. Cifuentes. "Covalent Polymer-Drug Conjugates". Molecules 10, n.º 1 (31 de enero de 2005): 114–25. http://dx.doi.org/10.3390/10010114.

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Končič, Marijana, Branka Zorc y Predrag Novak. "Macromolecular prodrugs. XIII. Hydrosoluble conjugates of 17β-estradiol and estradiol-17β-valerate with polyaspartamide polymer". Acta Pharmaceutica 61, n.º 4 (1 de diciembre de 2011): 465–72. http://dx.doi.org/10.2478/v10007-011-0039-x.

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Macromolecular prodrugs. XIII. Hydrosoluble conjugates of 17β-estradiol and estradiol-17β-valerate with polyaspartamide polymerTwo hydrosoluble conjugates of 17β-estradiol (ED) and estradiol-17β-valerate (EV) with polyaspartamide polymer were prepared and characterized. ED and EV were first chemically modified and bound to poly[α,β-(N-2-hydroxyethyl-DL-aspartamide)]-poly[α,β-(N-2-aminoethyl-DL-aspartamide)] (PAHA), a hydrosoluble polyaspartamide-type copolymer bearing both hydroxyl and amino groups. ED was first converted to 17-hemisuccinate (EDS) and then bound to PAHA. In the resulting conjugate PAHA-EDS, the estradiol moiety was linked to the polymer through a 2-aminoethylhemisuccinamide spacer. On the other hand, EV was first converted to estradiol-17β-valerate-3-(benzotriazole-1-carboxylate), which readily reacted with amino groups in PAHA affording the polymer-drug conjugate PAHA-EV. In the prepared conjugate PAHA-EV, the estradiol moiety was covalently bound to the polyaspartamide backbone by carbamate linkage, through an ethylenediamine spacer. The polymer-drug conjugates were designed and prepared with the aim to increase water-solubility, bioavailability and to improve drug delivery of the lipophilic estrogen hormone.

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Kostková, H., L. Schindler, L. Kotrchová, M. Kovář, M. Šírová, L. Kostka y T. Etrych. "Star Polymer-Drug Conjugates with pH-Controlled Drug Release and Carrier Degradation". Journal of Nanomaterials 2017 (2017): 1–10. http://dx.doi.org/10.1155/2017/8675435.

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In this study, we describe the design, synthesis, and physicochemical and preliminary biological characteristics of new biodegradable, high-molecular-weight (HMW) drug delivery systems with star-like architectures bearing the cytotoxic drug doxorubicin (DOX) attached by a hydrazone bond-containing spacer. The star polymers were synthesized by grafting semitelechelic N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers on a 2,2-bis(hydroxymethyl)propionic acid- (bis-MPA-) based polyester dendritic core. The molecular weight of the star polymers ranged from 280 to 450 000 g/mol and could be adjusted by proper selection of the bis-MPA dendrimer generation and by considering the polymer to dendrimer molar ratio. The biodegradation of the polymer conjugates is based on the spontaneous slow hydrolysis of the dendritic core in neutral physiological conditions. Hydrazone spacers in the conjugates were fairly stable at neutral pH (7.4) mimicking blood stream conditions, and DOX was released from the conjugates under mild acidic conditions simulating the tumor cell microenvironment in endosomes and lysosomes (pH 5). Finally, we have shown the significant in vitro cytotoxicity of the star polymer-DOX conjugate on selected cancer cell lines with IC50 values almost comparable with that of the free drug and higher than that observed for a linear polymer-DOX conjugate with much lower molecular weight.

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Kumar, Sahil, Alka Sharma, Rajesh K. Singh, DN Prasad y TR Bhardwaj. "Synthesis and in vitro drug release studies on substituted polyphosphazene conjugates of lumefantrine." International Journal of Drug Delivery 9, n.º 2 (6 de octubre de 2017): 36. http://dx.doi.org/10.5138/09750215.2133.

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The present study pertains to the delivery of antimalarial drug (Lumifantrine). In this, polyphosphazene has been used in the synthesis of polyphosphazene-linked conjugates of Lumifantrine. These polymer-linked Conjugates have been synthesized and characterized by modern analytical techniques. The in-vitro drug release of Lumifantrine drug conjugates: p-Amino benzoic acid ester substituted polyphosphazene drug conjugate (15) and Glycine methyl ester substituted polyphosphazene drug conjugate (21) have been found to be 6.00 % and 5.96% (pH 1.2), 88.52% and 79.86% (pH 7.4), respectively. These drug conjugate may prove an effective delivery system for the treatment of malaria.

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Grigoletto, Antonella, Gabriele Martinez, Daniela Gabbia, Tommaso Tedeschini, Michela Scaffidi, Sara De Martin y Gianfranco Pasut. "Folic Acid-Targeted Paclitaxel-Polymer Conjugates Exert Selective Cytotoxicity and Modulate Invasiveness of Colon Cancer Cells". Pharmaceutics 13, n.º 7 (23 de junio de 2021): 929. http://dx.doi.org/10.3390/pharmaceutics13070929.

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Although selective tumor delivery of anticancer drugs has been sought by exploiting either passive targeting or by ligand-mediated targeting, a selective anticancer therapy remains an unmet medical need. Despite the advances which have been achieved by nanomedicines, nanosystems such as polymer-drug conjugates still miss the goal of clinical efficacy. In this study, we demonstrated that polymer-drug conjugates require a thoroughly chemical design and the right targeting agent/polymer ratio to be selective and effective towards cancer cells. In particular, two PEG conjugates carrying paclitaxel and targeted with different folic acid (FA)/PEG ratios (one or three) were investigated. The cytotoxicity study in positive (HT-29) and negative (HCT-15) FA receptor (FR)-cell lines demonstrated that the conjugates with one or three FAs were 4- or 28-fold more active in HT-29 cells, respectively. The higher activity of the 3-FA conjugate was confirmed by its strong impact on cell cycle arrest. Furthermore, FA targeting had a clear effect on migration and invasiveness of HT-29 cells, which were significantly reduced by both conjugates. Interestingly, the 3-FA conjugate showed also an improved pharmacokinetic profile in mice. The results of this study indicate that thorough investigations are needed to optimize and tune drug delivery and achieve the desired selectivity and activity towards cancer cells.

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Wadhwa, Saurabh y Russell J. Mumper. "Polymer-Drug Conjugates for Anticancer Drug Delivery". Critical Reviews in Therapeutic Drug Carrier Systems 32, n.º 3 (2015): 215–45. http://dx.doi.org/10.1615/critrevtherdrugcarriersyst.2015010174.

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Böhmová, Eliška, Robert Pola, Michal Pechar, Jozef Parnica, Daniela Machová, Olga Janoušková y Tomáš Etrych. "Polymer Cancerostatics Containing Cell-Penetrating Peptides: Internalization Efficacy Depends on Peptide Type and Spacer Length". Pharmaceutics 12, n.º 1 (10 de enero de 2020): 59. http://dx.doi.org/10.3390/pharmaceutics12010059.

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Cell-penetrating peptides (CPPs) are commonly used substances enhancing the cellular uptake of various cargoes that do not easily cross the cellular membrane. CPPs can be either covalently bound directly to the cargo or they can be attached to a transporting system such as a polymer carrier together with the cargo. In this work, several CPP–polymer conjugates based on copolymers of N-(2-hydroxypropyl)methacrylamide (pHPMA) with HIV-1 Tat peptide (TAT), a minimal sequence of penetratin (PEN), IRS-tag (RYIRS), and PTD4 peptide, and the two short hydrophobic peptides VPMLK and PFVYLI were prepared and characterized. Moreover, the biological efficacy of fluorescently labeled polymer carriers decorated with various CPPs was compared. The experiments revealed that the TAT–polymer conjugate and the PEN–polymer conjugate were internalized about 40 times and 15 times more efficiently than the control polymer, respectively. Incorporation of dodeca(ethylene glycol) spacer improved the cell penetration of both studied polymer–peptide conjugates compared to the corresponding spacer-free polymer conjugates, while the shorter tetra(ethylene glycol) spacer improved only the penetration of the TAT conjugate but it did not improve the penetration of the PEN conjugate. Finally, a significantly improved cytotoxic effect of the polymer conjugate containing anticancer drug pirarubicin and TAT attached via a dodeca(ethylene glycol) was observed when compared with the analogous polymer–pirarubicin conjugate without TAT.

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Tesis sobre el tema "Drug-Polymer conjugates"

Devenish, Sean. "Studies of natural product derivatives: targeted polymer drug conjugates". Thesis, University of Canterbury. Chemistry, 2004. http://hdl.handle.net/10092/6661.

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Polymer drug conjugates are an emerging class of therapeutic agent that offer advantages in the treatment of cancer through long circulation times and passive targeting. A further benefit of using a polymeric framework is that it readily allows attachment of targeting motifs to enhance the drug specificity, as well as allowing variation of the drug component. In this work a series of targeted polymer drug conjugates were prepared that incorporated different drugs via peptide linkers designed to be stable in circulation but degradable at the target site. In order to ensure stability in circulation, it was necessary to ensure the drugs were conjugated to the biodegradable linkers via amides, which required the introduction of amine functionalities to the natural-product drugs. The required hemisyntheses were successfully carried out, although yields were sometimes disappointing. An effort to allow an assessment of the pharmacokinetic effects of using a polymeric scaffold was made through the attempted synthesis of low molecular weight analogues of the polymer drug conjugates, with success in some cases. A recently developed polymeric precursor was used in the preparation of the polymer drug conjugates but was found to undergo an unexpected side-reaction, which may prevent the long term development of this particular precursor. The desired conjugates were nonetheless successfully produced on a scale suitable for initial biological testing. Both the high and low molecular weight constructs synthesised showed reduced cytotoxicities to P388 murine leukemia cells and are currently awaiting in vitro testing to truly evaluate their utility.

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Gilbert, Helena Rosalind Petra. "Bioresponsive polymer-protection conjugates as a unimolecular drug delivery system". Thesis, Cardiff University, 2007. http://orca.cf.ac.uk/55685/.

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PEGylation has become very popular for the generation of nanomedicines with improved protein delivery properties, despite its lack of biodegradability. Researchers usually try to maximise retained protein activity during PEGylation. However, this proof of principle study aimed to create an inactive peptide or enzyme product, using a biodegradable polymer, that would elicit minimal activity/non-specific toxicity on administration. Following triggered site-specific degradation of the polymer, the hypothesis was that protein activity could be slowly regenerated in the general circulation or localised to a specific target site. Model conjugates were synthesised by coupling dextrin degraded by amylase to trypsin and melanocyte stimulating hormone MSH, to test this concept and targeted delivery for both an enzyme and a receptor-binding ligand. Hyaluronic acid HA degraded by hyaluronidase conjugates of trypsin and ribonuclease A were also synthesised. The latter was intended to develop the possibility of designing novel anti cancer conjugates. A higher molecular weight dextrin 47,200 g/mol, 26 mol succinoylation was shown to best mask 34 trypsin activity and reinstate 58 of the activity by addition of amylase. When a HA fraction molecular weight 130,000 g/mol was prepared by acid hydrolysis and conjugated to trypsin 4 w/w, trypsin activity was masked to 6 and immediately re-instated to 24 on addition of hyaluronidase. Similarly, the dextrin-MSH conjugate reduced melanin production to 11 of the control and only restored to 33 on addition of amylase. RNase A alone was not cytotoxic up to 1 mg/mL, whereas, the HA-RNase A conjugate 0.1 mg/mL RNase A equivalent was cytotoxic in B16F10 and CV-1 cells 72 h. This work provides proof of principle for the concept of using biodegradable polymers to mask and reinstate conjugated protein activity in the presence of the appropriate enzyme 'unmasking' trigger.

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Chau, Ying. "Targeted drug delivery by novel polymer-drug conjugates containing linkers cleavable by disease-associated enzymes". Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/32332.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2005.
Includes bibliographical references.
We have conceptualized a new class of polymer-linker-drug conjugates to achieve targeted drug delivery for the systemic treatment of cancer and other inflammatory diseases. The physiochemical properties of the polymer allow the conjugate to circulate longer in the body by minimizing renal and hepatic clearance, thereby improving the pharmacokinetics of the attached drugs. Traditionally, linkers are degraded by acidity or by some ubiquitous intracellular enzymes. We incorporate linkers that are sensitive to a specific extracellular enzyme whose overexpression is co-localized with the diseased tissue. The drug molecules remain inactive when attached to the polymer, thus preventing normal tissues from harmful side effects. When the conjugate is transported to the diseased area where there is a high level of the target enzyme, the linkers are cleaved to release the drugs at the specific site. As an example, we designed and synthesized two generations of novel polymer-peptide-drug conjugates for the tumor-targeted delivery of chemotherapeutics. To allow for passive targeting and enhanced permeation and retention (EPR), dextran with a size greater than 6 nm was selected as the polymeric carrier. This biocompatible and biodegradable carrier was chemically modified to allow for conjugation with doxorubicin and methotrexate, two common chemotherapeutics with undesirable side effects.
(cont.) Since matrix-metalloproteinases (MMPs) are associated with a number of types of cancer and their functions are essential to disease progression, including degrading extracellular matrix, releasing angiogenic factors and activating growth factors, we explored the possibility of MMP-mediated drug release. The synthesis procedures combined solid phase and solution phase techniques to enable flexibility in the linker design and in the charge modification of the polymer. This scaleable and robust process produced new conjugates that demonstrated excellent stability under physiological conditions and optimized sensitivity to enzymatic cleavage by MMP-2 and MMP-9. The new conjugate, dextran-peptide-methotrexate, was assessed for its in vivo anti-tumor efficacy and systemic side effects. It was compared to free methotrexate and a similar conjugate, differing by an MMP-insensitive linker, at equivalent intraperitoneal dosages administered weekly. The MMP-sensitive conjugate resulted in effective inhibition of in vivo tumor growth in each of the two separate tumor models that overexpress MMP-2 and MMP-9 (HT-1080 and U- 87). In contrast, free methotrexate resulted in no significant tumor reduction in the same models. Neither free methotrexate nor the conjugate caused any tumor inhibition in mice bearing RT- 112, a slower-growing model which expresses significantly less MMP than HT-1080 and U-87 . The anti-proliferative effect of the drug contributed to the inhibition of tumor growth. Systemic side effects caused by the MMP-sensitive conjugates were tolerable.
(cont.) MMP-insensitive conjugates, though able to inhibit tumor growth, caused toxicity in the small intestine and bone marrow and the experiment was terminated after one injection. We conducted a biodistribution study in HT-1080 bearing mice to investigate the targeting mechanism of the new conjugate. Independent of the linker sequence, passive targeting was evidenced by the prolonged plasma circulation and higher tissue accumulations of the conjugates in comparison with free methotrexate. The ratios of drug accumulation at the tumor versus the major site of side effects (small intestine) for both conjugates were enhanced by the EPR effects. The difference in the drug accumulation at the tumor site was insignificant between conjugates with MMP-sensitive and MMP-insensitive linkers. We concluded that the tumor targeting effect of the dextran-peptide-methotrexate conjugate was dominantly due to passive targeting and EPR. The difference in the systemic side effects observed for the conjugates with different linkers was attributed to their varying susceptibility towards enzymes in normal tissues.
by Ying Chau.
Ph.D.

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Sat, Nee Yee. "Factors that influence tumour targeting by the enhanced permeability and retention (EPR) effect". Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325320.

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Mina, James. "Hyaluronic acid based polymer drug conjugates for the treatment of rheumatoid arthritis". Thesis, University of the West of Scotland, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.739391.

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Singh, Jennifer. "Polymer-drug conjugates based on hyaluronic acid for the treatment of rheumatoid arthritis". Thesis, University of the West of Scotland, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415937.

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The work represents an initial appraisal ofhow polymer-drug conjugates based upon hyaluronic acid (HA) may behave at sites of inflammation relative to unmodified HA. Three polymer drug conjugates were synthesized in which a model drug, p-nitroaniline (pNA) has been joined to HA via a peptide spacer group containing alanine (ala) and valine (val). The conjugates are: HA-ala-pNA, HA-val-ala-pNA, and HA-ala-ala-ala-pNA. Each of the conjugates was subjected to the degradative effects of both hyaluronidase and hydroxyl radicals by the Fenton reaction (generated by Fe2 + ions and H202) . Hyaluronidase digestion was followed both by measurement of reducing hexosamine end-groups and rheologically. The degradative effects of hydroxyl radicals were followed by rheology alone. On incubation with hyaluronidase, end-group analysis showed that the rate of degradation of HA-ala-ala-ala-pNA preparation did not appear to differ significantly from that of unmodified HA. The hyaluronic acid-val-ala-pNA sample appeared to show a higher degradation rate than HA itself initially, after which it slowed relative to HA itself. With HA-ala-pNA the rate of hydrolysis of the HA backbone was found to be considerably lower that that observed for the other materials. Viscometric studies on the effects of hydroxyl radicals showed that, as expected, the rate of decrease in viscosity of the unmodified HA increased with increasing [Fe2J and that H202 alone showed a depolymerising effect on the HA in a concentration-dependent manner. The initial viscosity of the HA-ala-pNA and HA-ala-ala-ala-pNA was considerably lower than that of the unmodified H.-and hence any degradation was difficult to follow although some effects could Q\? observed with the higher concentrations of Fe::+. The HA-\al-ala-pNA conjugate showed a higher initial viscosity than native HA. The reason for this is not clear and would require more experimentation. Like the unmodified hyaluronic acid, on exposure to hydroxyl radicals, a rapid initial depolymerization of the conjugates was observed the rate of which increased with increasing concentration of Fe:!+.

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Jacobs, Jaco. "Poly(N-vinylpyrrolidone) - Poly(γ-benzyl-L-glutamate) conjugates". Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/20369.

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Thesis (MSc)--Stellenbosch University, 2012.
ENGLISH ABSTRACT: The combination of natural and synthetic polymers allow for the synthesis of advanced hybrid copolymers. These hybrid copolymers have applications in biomedical areas, one such area being in drug delivery systems (DDS). In this study, a modular approach was used to prepare amphiphilic block copolymers with the ability to self-assemble into three dimensional structures. Reversible addition-fragmentation chain transfer (RAFT) was the synthetic tool used to mediate the polymerization of N-vinylpyrrolidone. RAFT is a versatile method to prepare polymers with control over molecular weight and dispersity. A xanthate chain transfer agent (CTA) was used to obtain the hydrophilic poly(N-vinylpyrrolidone) (PVP) block. An aldehyde functionality could be introduced due to the lability of the xanthate moiety, the procedure of which was effectively optimized to produce quantitative conversion. A dixanthate CTA was synthesized to produce a PVP chain which after the modification reaction, resulted in a α,ω-telechelic polymer. A polypeptide was synthesized via the ring-opening polymerization of Ncarboxyanhydrides (ROP NCA). The living and controllable ROP of NCAs is a method which results in polypeptides, but without a well-defined amino acid order. Poly(γ- benzyl-L-glutamate) (PBLG) was synthesized with a narrow dispersity (Đ = 1.10 – 1.15) using conditions that promote the retention of a terminal primary amine. A protected cysteine functionality was introduced via the terminal amine PBLG chain-end, using peptide synthesis techniques. This resulted in the conjugation of the aldehyde functional PVP and the cysteine terminal PBLG using a covalent, non-reducible thiazolidine linkage. The deprotection of the cysteine, more specifically the deprotection of the thiol was a non-trivial procedure. The thiol protecting acetamidomethyl (Acm) group could not be cleaved using traditional methods, but instead a modified procedure was developed to effectively remove the Acm group while inhibiting hydrolysis of the benzyl esters. It was determined that the conjugation reaction could effectively proceed in N,Ndimethylformamide (DMF) at a slightly elevated temperature and so continued to prepare the amphiphilic hybrid block copolymers, PVP-b-PBLG. A structurally different PBLG chain, namely PBLG-b-Cys was conjugated to the ω-aldehyde PVP and the conjugation efficiency was compared to our PBLG-Cys block. In the case of PBLG-b- Cys the in situ deprotection and conjugation as well as a two-step deprotection and conjugation reaction with PVP resulted in very low conjugation efficiency. The cysteine end-functional PBLG resulted in near quantitative conjugation with PVP. The critical micelle concentration (CMC) for PVP90-b-PBLG54 was determined to be 6 μg/mL, using fluorescence spectroscopy. Particle sizes were determined with TEM and DLS and found to range from 25 nm to 120 nm depending on the polymer block lengths as well as hydrophobic/hydrophilic block length ratios. Furthermore, when the micelles were subjected to an increased acidic environment, the labile benzyl ester bonds were hydrolyzed. This was observed with TEM where the particle sizes increased 10-fold to form vesicular structures. Hydrolysis was further confirmed with ATR-FTIR and 1H-NMR spectroscopy. Cytotoxicity tests confirmed that the copolymer micelles had good cell compatibility at high concentrations such as 0.9 mg/mL. Investigation into drug loading using a pyrene probe confirmed the viability of using PVP-b-PBLG as a responsive DDS.
AFRIKAANSE OPSOMMING: Die kombinasie van natuurlike en sintetiese polimere maak dit moontlik vir die sintese van gevorderde hibried kopolimere. Hierdie kopolimere het aanwending in biomediese gebiede, een so 'n gebied is in medisinale vervoer sisteme (MVS). 'n Modulêre benadering is in hierdie studie gebruik om amfifiliese blok kopolimere te berei. Omkeerbare addisie-fragmentasie kettingoordrag (OAFO) is gebruik as die sintetiese tegniek vir die polimerisasie van N-vinielpirolidoon (NVP). OAFO is 'n veelsydige metode om polimere te berei met beheer oor molekulêre gewig en dispersiteit (Đ). 'n Xantaat kettingoordrag agent (KOA) is gebruik om die hidrofiliese poli(N-vinielpirolidoon) (PVP) blok te sintetiseer. ‘n Aldehied endgroep was deur die terminale xantaat funksionaliteit berei, ‘n proses wat geoptimiseer is tot kwantitatiewe omsetting. 'n Di-xantaat KOA is gesintetiseer om, na modifikasie, 'n α, ω-telecheliese polimeer te produseer. Die polipeptied was gesintetiseer deur middel van ’n ringopening polimerisasie van Nkarboksianhidriede (ROP NKA). Die lewende en beheerbare ROP van NKAe is 'n metode wat lei tot polipeptiede sonder ’n gedefinieerde aminosuur volgorde. Poli(γ- benzyl-L-glutamaat) met 'n lae dispersiteit (Đ = 1.10 – 1.15), is gesintetiseer deur gebruik te maak van kondisies wat die behoud van 'n terminale primêre amien bevorder. 'n Beskermde sistien-funksionaliteit is ingebou via die terminale amien met behulp van peptiedsintese tegnieke. Die tiol beskerming van die asetamidometiel (Asm) groep kon nie gekleef word deur gebruik te maak van tradisionele metodes nie, maar ‘n nuwe proses is ontwikkel om die Asm groep te kleef sowel as om die hidrolise van die bensiel esters te inhibeer. Die koppelings reaksie het effektief verloop in DMF by 'n effens verhoogde temperatuur en sodoende is die amfifiliese hibried blok-kopolimere, PVP-b-PBLG berei. Twee verskillende PBLG kettings is gekoppel aan die ω-aldehied PVP en die koppeling doeltreffendheid is vergelyk. Daar is bevind dat net die sistien end-funksionele PBLG tot kwantitatiewe konjugasie kon lei. Die kritiese misel konsentrasie is bepaal vir PVP90-b-PBLG54 as 6 μg/mL met behulp van fluoressensie spektroskopie. Die deeltjie-groottes is bepaal met TEM en DLS en wissel van 25 nm tot 120 nm, afhangende van die polimeer bloklengtes sowel as hidrofobiese / hidrofiliese blok lengte verhoudings. Die miselle is blootgestel aan 'n verhoogde suur omgewing, wat tot die hidrolise van die bensiel ester groepe gelei het. TEM het getoon dat die deeltjie-groottes met 10-voud vergroot het tot vesikulêre strukture. Hidrolise is verder bevestig met ATR-FTIR en 1H-KMR spektroskopie. Sitotoksiese toetse het bevestig dat die miselle geen of min toksisiteit toon teenoor eukariotiese selle nie, selfs teen 'n hoë konsentrasies soos 0.9 mg/ml. Die medisinale behoud vermoë is met behulp van pireen bevestig en dus ook die potensiaal van PVP-b-PBLG as ‘n moontlike MVS.

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Heinrich, Anne-Kathrin [Verfasser]. "Overcoming drug resistance by stimulus-sensitive drug delivery systems : a preclinical characterization of polymer-drug conjugates for the treatment of multi-drug resistant cancer / Anne-Kathrin Heinrich". Halle, 2017. http://d-nb.info/1144955262/34.

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Krishnan, Vinu. "Design and Synthesis of Nanoparticle “PAINT-BRUSH” Like Multi-Hydroxyl Capped Poly(Ethylene Glycol) Conjugates for Cancer Nanotherapy". Akron, OH : University of Akron, 2008. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=akron1217677351.

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Thesis (M.S.)--University of Akron, Dept. of Biomedical Engineering, 2008.
"August, 2008." Title from electronic thesis title page (viewed 12/9/2009) Advisor, Stephanie T. Lopina; Committee members, Amy Milsted, Daniel B. Sheffer, Daniel Ely; Department Chair, Daniel B. Sheffer; Dean of the College, George K. Haritos; Dean of the Graduate School, George R. Newkome. Includes bibliographical references.

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Park, Jongryul. "Poly(2-oxazoline) architectures for drug delivery systems". Thesis, Queensland University of Technology, 2021. https://eprints.qut.edu.au/211439/1/Jongryul_Park_Thesis.pdf.

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The overall aim of my PhD research was to develop biocompatible materials, namely poly(2-oxazoline)s, in terms of chemical structures and chemical and physical properties for drug delivery systems. This thesis demonstrated novel strategies and unique approaches towards sophisticated drug delivery formulations. A combination of crosslinking chemistry, thermoresponsive properties, and drug conjugation was introduced to overcome common issues in typical drug delivery devices such as burst drug release and low drug efficiency. Ultimately, this thesis aimed to promote poly(2-oxazoline)s as the most promising emerging polymers in the future.

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Libros sobre el tema "Drug-Polymer conjugates"

Ronit, Satchi-Fainaro y Duncan R, eds. Polymer therapeutics II: Polymers as drugs, conjugates, and gene delivery systems. Berlin: Springer, 2006.

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Wang, Chun y Youqing Shen. Polymer-Drug Conjugates. Springer London, Limited, 2020.

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Chopra, Neetu, Jitender Madan, Ashish Baldi y Monika Chaudhary. Polymer-Drug Conjugates: Linker Chemistry, Protocols and Applications. Elsevier Science & Technology, 2023.

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Chopra, Neetu, Jitender Madan, Ashish Baldi y Monika Chaudhary. Polymer-Drug Conjugates: Linker Chemistry, Protocols and Applications. Elsevier Science & Technology Books, 2023.

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(Editor), Ronit Satchi-Fainaro y Ruth Duncan (Editor), eds. Polymer Therapeutics I: Polymers as Drugs, Conjugates and Gene Delivery Systems (Advances in Polymer Science). Springer, 2006.

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Duncan, Ruth y Ronit Satchi-Fainaro. Polymer Therapeutics I: Polymers as Drugs, Conjugates and Gene Delivery Systems. Springer, 2010.

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Duncan, Ruth y Ronit Satchi-Fainaro. Polymer Therapeutics II: Polymers as Drugs, Conjugates and Gene Delivery Sytems. Springer, 2010.

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(Editor), Ronit Satchi-Fainaro y Ruth Duncan (Editor), eds. Polymer Therapeutics II: Polymers as Drugs, Conjugates and Gene Delivery Sytems (Advances in Polymer Science) (Advances in Polymer Science). Springer, 2006.

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Capítulos de libros sobre el tema "Drug-Polymer conjugates"

Fante, Cristina y Francesca Greco. "Polymer-Drug Conjugates". En Engineering Polymer Systems for Improved Drug Delivery, 55–83. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2014. http://dx.doi.org/10.1002/9781118747896.ch3.

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Fante, Cristina y Francesca Greco. "Polymer-Drug Conjugates". En Fundamentals of Pharmaceutical Nanoscience, 159–82. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4614-9164-4_7.

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Kopeček, Jindřich y Pavla Kopečková. "Design of Polymer-Drug Conjugates". En Drug Delivery in Oncology, 483–512. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2011. http://dx.doi.org/10.1002/9783527634057.ch17.

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Duncan, Ruth. "Polymer-Drug Conjugates: Targeting Cancer". En Biomedical Aspects of Drug Targeting, 193–209. Boston, MA: Springer US, 2002. http://dx.doi.org/10.1007/978-1-4757-4627-3_10.

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Mohanty, Anjan Kumar, Fahima Dilnawaz, Guru Prasad Mohanta y Sanjeeb Kumar Sahoo. "Polymer–Drug Conjugates for Targeted Drug Delivery". En Advances in Delivery Science and Technology, 389–407. Cham: Springer International Publishing, 2014. http://dx.doi.org/10.1007/978-3-319-11355-5_12.

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Singh, Sauraj, Ruchir Priyadarshi, Bijender Kumar, Saleheen Bano, Farha Deeba, Anurag Kulshreshtha y Yuvraj Singh Negi. "Polymer–Drug Conjugates as Drug Delivery Systems". En Applications of Encapsulation and Controlled Release, 61–75. Boca Raton : CRC Press, Taylor & Francis Group, 2019.: CRC Press, 2019. http://dx.doi.org/10.1201/9780429299520-4.

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Abu Ajaj, Khalid y Felix Kratz. "Clinical Experience with Drug-Polymer Conjugates". En Drug Delivery in Oncology, 839–84. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2011. http://dx.doi.org/10.1002/9783527634057.ch26.

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Francis, Arul Prakash y A. Jayakrishnan. "Chapter 11. Polymer–Drug Conjugates for Treating Local and Systemic Fungal Infections". En Biomaterials Science Series, 303–24. Cambridge: Royal Society of Chemistry, 2019. http://dx.doi.org/10.1039/9781788012638-00303.

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Swami, Rajan, Dinesh Kumar, Wahid Khan, Ramakrishna Sistla y Nalini Shastri. "Polymer–Drug Conjugate in Focal Drug Delivery". En Advances in Delivery Science and Technology, 117–47. Boston, MA: Springer US, 2013. http://dx.doi.org/10.1007/978-1-4614-9434-8_5.

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pun, Suzie H. y Allan S. Hoffman. "Polymer–Drug Conjugates". En Biomaterials Science, 1036–39. Elsevier, 2013. http://dx.doi.org/10.1016/b978-0-08-087780-8.00092-9.

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Actas de conferencias sobre el tema "Drug-Polymer conjugates"

Yurkovetskiy, Alex, Natalya Bodyak, Mao Yin, Joshua Thomas, Patrick Conlon, Cheri Stevenson, Alex Uttard et al. "Abstract 4331: Advantages of polyacetal polymer-based antibody drug conjugates employing cysteine bioconjugation." En Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-4331.

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Fang, Yang y Xiaobo Tan. "Design and Modeling of a Petal-Shape, Conjugated Polymer-Actuated Micropump". En ASME 2008 Dynamic Systems and Control Conference. ASMEDC, 2008. http://dx.doi.org/10.1115/dscc2008-2278.

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Conjugated polymers are emerging actuation materials for biomimetic robots and biomedical devices. Most previous research has been focused on the configurations of cantilever beams and linear extenders. However, the diaphragm configuration is needed in many potential applications, such as micro pumps for drug delivery and chemical/ biological analysis. In this paper the design of a conjugated polymer pumping diaphragm is investigated theoretically and experimentally. A petal-shape design is proposed to alleviate the edge constrains. Transfer function models from the actuation voltage to the diaphragm curvature and to the flow rate are obtained. Experiments are conducted to verify the effectiveness of the models. The transfer function models facilitate design optimization and the use of feedback control tools in dealing with the complicated behavior of conjugated polymer actuators.

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Lam, Robert, Xueqing Zhang, Mark Chen y Dean Ho. "Functional Nanodiamond Internalization Mechanisms and Kinetics". En ASME 2010 First Global Congress on NanoEngineering for Medicine and Biology. ASMEDC, 2010. http://dx.doi.org/10.1115/nemb2010-13339.

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Several reports have described the relationship between size, aspect ratio, surface modification and internalization for a variety of nanoparticles (i.e. gold, polymer, carbon nanotubes). Nanodiamonds (NDs) in particular have recently been implicated in a variety of biomedical applications. One of the most promising is in utilizing NDs as drug delivery carriers where successful internalization is of utmost importance. A few reports recently have demonstrated the energy dependent internalization of bare NDs. In this report, we investigate the internalization mechanism and kinetics of functional ND-conjugate translocation.

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Thomas, Joshua, Alex Yurkovetskiy, Natalya Bodyak, Mao Yin, Patrick Conlon, Cheri Stevenson, Alex Uttard et al. "Abstract C238: Polyacetal polymer-based anti-HER2 antibody-drug conjugate employing cysteine bioconjugation through thioether linkage allows a high drug loading of dolastatin-derived payload with excellent pharmacokinetics and potent anti-tumor activity." En Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Oct 19-23, 2013; Boston, MA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1535-7163.targ-13-c238.

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Informes sobre el tema "Drug-Polymer conjugates"

Nan, Anjan. Targetable Polymer-Antiangiogenic Drug Conjugates for Systemic Breast Cancer Therapy. Fort Belvoir, VA: Defense Technical Information Center, septiembre de 2006. http://dx.doi.org/10.21236/ada462903.

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Li, Chun. Radiation-Induced Chemosensitization: Potentiation of Antitumor Activity of Polymer-Drug Conjugates. Fort Belvoir, VA: Defense Technical Information Center, abril de 2002. http://dx.doi.org/10.21236/ada406209.

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Li, Chun. Radiation Induced Chemosensitization: Potentiation of Antitumor Activity of Polymer-Drug Conjugates. Fort Belvoir, VA: Defense Technical Information Center, abril de 2003. http://dx.doi.org/10.21236/ada415707.

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