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Journal articles on the topic 'Drug-Polymer conjugates'

Author: Grafiati

Published: 25 May 2024

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1

Libánská, Alena, Eva Randárová, Franck Lager, Gilles Renault, Daniel Scherman, and Tomáš Etrych. "Polymer Nanomedicines with Ph-Sensitive Release of Dexamethasone for the Localized Treatment of Inflammation." Pharmaceutics 12, no. 8 (July 25, 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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2

Duncan, Ruth. "Drug-polymer conjugates." Anti-Cancer Drugs 3, no. 3 (June 1992): 175–210. http://dx.doi.org/10.1097/00001813-199206000-00001.

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3

Duncan, R. "Designing polymer conjugates as lysosomotropic nanomedicines." Biochemical Society Transactions 35, no. 1 (January 22, 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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4

Elvira, C., A. Gallardo, J. Roman, and A. Cifuentes. "Covalent Polymer-Drug Conjugates." Molecules 10, no. 1 (January 31, 2005): 114–25. http://dx.doi.org/10.3390/10010114.

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5

Končič, Marijana, Branka Zorc, and Predrag Novak. "Macromolecular prodrugs. XIII. Hydrosoluble conjugates of 17β-estradiol and estradiol-17β-valerate with polyaspartamide polymer." Acta Pharmaceutica 61, no. 4 (December 1, 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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6

Kostková, H., L. Schindler, L. Kotrchová, M. Kovář, M. Šírová, L. Kostka, and 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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7

Kumar, Sahil, Alka Sharma, Rajesh K. Singh, DN Prasad, and TR Bhardwaj. "Synthesis and in vitro drug release studies on substituted polyphosphazene conjugates of lumefantrine." International Journal of Drug Delivery 9, no. 2 (October 6, 2017): 36. http://dx.doi.org/10.5138/09750215.2133.

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<p class="Default"><span>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 <em>in-vitro</em> drug release of Lumifantrine drug conjugates: <em>p</em>-Amino benzoic acid ester substituted polyphosphazene drug conjugate <strong>(15)</strong> and Glycine methyl ester substituted polyphosphazene drug conjugate <strong>(21) </strong>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.</span></p>

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8

Grigoletto, Antonella, Gabriele Martinez, Daniela Gabbia, Tommaso Tedeschini, Michela Scaffidi, Sara De Martin, and Gianfranco Pasut. "Folic Acid-Targeted Paclitaxel-Polymer Conjugates Exert Selective Cytotoxicity and Modulate Invasiveness of Colon Cancer Cells." Pharmaceutics 13, no. 7 (June 23, 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, and Russell J. Mumper. "Polymer-Drug Conjugates for Anticancer Drug Delivery." Critical Reviews in Therapeutic Drug Carrier Systems 32, no. 3 (2015): 215–45. http://dx.doi.org/10.1615/critrevtherdrugcarriersyst.2015010174.

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10

Böhmová, Eliška, Robert Pola, Michal Pechar, Jozef Parnica, Daniela Machová, Olga Janoušková, and Tomáš Etrych. "Polymer Cancerostatics Containing Cell-Penetrating Peptides: Internalization Efficacy Depends on Peptide Type and Spacer Length." Pharmaceutics 12, no. 1 (January 10, 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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11

Xu, Jiankun, Shanmeng Lin, Hao Hu, Qi Xing, and Jin Geng. "Tumor-Targeting Polymer–Drug Conjugate for Liver Cancer Treatment In Vitro." Polymers 14, no. 21 (October 25, 2022): 4515. http://dx.doi.org/10.3390/polym14214515.

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Bufalin (buf) has poor solubility in aqueous solution, poor tumor targeting, and many non-specific toxic and side effects. The advantages of high-molecular-weight polymer conjugates are that they can improve the water solubility of buf, prolong plasma half-life, and reduce non-specific toxicity. A novel water-soluble polymer–drug conjugate with buf and fluorescein pendants was prepared by the combination of reversible addition-fragmentation transfer (RAFT) polymerization and click chemistry. Its anticancer performance and cellular uptake behavior against liver cancer were investigated in vitro. The polymer–buf conjugates exhibit controlled release and tumor-targeting capabilities, showing promise for clinical applications.

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12

Chis, Adriana Aurelia, Anca Maria Arseniu, Claudiu Morgovan, Carmen Maximiliana Dobrea, Adina Frum, Anca Maria Juncan, Anca Butuca, Steliana Ghibu, Felicia Gabriela Gligor, and Luca Liviu Rus. "Biopolymeric Prodrug Systems as Potential Antineoplastic Therapy." Pharmaceutics 14, no. 9 (August 25, 2022): 1773. http://dx.doi.org/10.3390/pharmaceutics14091773.

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Nowadays, cancer represents a major public health issue, a substantial economic issue, and a burden for society. Limited by numerous disadvantages, conventional chemotherapy is being replaced by new strategies targeting tumor cells. In this context, therapies based on biopolymer prodrug systems represent a promising alternative for improving the pharmacokinetic and pharmacologic properties of drugs and reducing their toxicity. The polymer-directed enzyme prodrug therapy is based on tumor cell targeting and release of the drug using polymer–drug and polymer–enzyme conjugates. In addition, current trends are oriented towards natural sources. They are biocompatible, biodegradable, and represent a valuable and renewable source. Therefore, numerous antitumor molecules have been conjugated with natural polymers. The present manuscript highlights the latest research focused on polymer–drug conjugates containing natural polymers such as chitosan, hyaluronic acid, dextran, pullulan, silk fibroin, heparin, and polysaccharides from Auricularia auricula.

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13

Manandhar, Sajana, Erica Sjöholm, Johan Bobacka, Jessica M. Rosenholm, and Kuldeep K. Bansal. "Polymer-Drug Conjugates as Nanotheranostic Agents." Journal of Nanotheranostics 2, no. 1 (March 13, 2021): 63–81. http://dx.doi.org/10.3390/jnt2010005.

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Since the last decade, the polymer-drug conjugate (PDC) approach has emerged as one of the most promising drug-delivery technologies owing to several benefits like circumventing premature drug release, offering controlled and targeted drug delivery, improving the stability, safety, and kinetics of conjugated drugs, and so forth. In recent years, PDC technology has advanced with the objective to further enhance the treatment outcomes by integrating nanotechnology and multifunctional characteristics into these systems. One such development is the ability of PDCs to act as theranostic agents, permitting simultaneous diagnosis and treatment options. Theranostic nanocarriers offer the opportunity to track the distribution of PDCs within the body and help to localize the diseased site. This characteristic is of particular interest, especially among those therapeutic approaches where external stimuli are supposed to be applied for abrupt drug release at the target site for localized delivery to avoid systemic side effects (e.g., Visudyne®). Thus, with the help of this review article, we are presenting the most recent updates in the domain of PDCs as nanotheranostic agents. Different methodologies utilized to design PDCs along with imaging characteristics and their applicability in a wide range of diseases, have been summarized in this article.

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14

Heath, Felicity, Amy Newman, Chiara Clementi, Gianfranco Pasut, Hong Lin, Gary J. Stephens, Benjamin J. Whalley, Helen M. I. Osborn, and Francesca Greco. "A novel PEG–haloperidol conjugate with a non-degradable linker shows the feasibility of using polymer–drug conjugates in a non-prodrug fashion." Polymer Chemistry 7, no. 47 (2016): 7204–10. http://dx.doi.org/10.1039/c6py01418f.

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A PEG–haloperidol conjugate was synthesised, which retains binding to the dopamine D₂receptor, showing the possibility of using polymer-drug conjugates as drugsper se' rather than as prodrugs.

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15

Sharma, Rajiv, Nishu Singla, Sahil Mehta, Tripti Gaba, Ravinder Rawal, H. S. Rao, and T. R. Bhardwaj. "Recent Advances in Polymer Drug Conjugates." Mini-Reviews in Medicinal Chemistry 15, no. 9 (May 25, 2015): 751–61. http://dx.doi.org/10.2174/1389557515666150519104507.

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16

Minko, Tamara. "Soluble polymer conjugates for drug delivery." Drug Discovery Today: Technologies 2, no. 1 (March 2005): 15–20. http://dx.doi.org/10.1016/j.ddtec.2005.05.005.

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17

Pitt, Colin G., Jason Wertheim, C. T. Wang, and Subodh S. Shah. "Polymer-drug conjugates: Manipulation of drug delivery kinetics." Macromolecular Symposia 123, no. 1 (September 1997): 225–34. http://dx.doi.org/10.1002/masy.19971230122.

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18

Nicosia, Angelo, Giuseppe La Perna, Lorena Maria Cucci, Cristina Satriano, and Placido Mineo. "A Multifunctional Conjugated Polymer Developed as an Efficient System for Differentiation of SH-SY5Y Tumour Cells." Polymers 14, no. 20 (October 14, 2022): 4329. http://dx.doi.org/10.3390/polym14204329.

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Polymer-based systems have been demonstrated in novel therapeutic and diagnostic (theranostic) treatments for cancer and other diseases. Polymers provide a useful scaffold to develop multifunctional nanosystems that combine various beneficial properties such as drug delivery, bioavailability, and photosensitivity. For example, to provide passive tumour targeting of small drug molecules, polymers have been used to modify and functionalise the surface of water-insoluble drugs. This approach also allows the reduction of adverse side effects, such as retinoids. However, multifunctional polymer conjugates containing several moieties with distinct features have not been investigated in depth. This report describes the development of a one-pot approach to produce a novel multifunctional polymer conjugate. As a proof of concept, we synthesised polyvinyl alcohol (PVA) covalently conjugated with rhodamine B (a tracking agent), folic acid (a targeting agent), and all-trans retinoic acid (ATRA, a drug). The obtained polymer (PVA@RhodFR) was characterised by MALDI-TOF mass spectrometry, gel permeation chromatography, thermal analysis, dynamic light-scattering, NMR, UV-Vis, and fluorescence spectroscopy. Finally, to evaluate the efficiency of the multifunctional polymer conjugate, cellular differentiation treatments were performed on the neuroblastoma SH-SY5Y cell line. In comparison with standard ATRA-based conditions used to promote cell differentiation, the results revealed the high capability of the new PVA@RhodFR to induce neuroblastoma cells differentiation, even with a short incubation time and low ATRA concentration.

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19

Šubr, Vladimír, Robert Pola, Shanghui Gao, Rayhanul Islam, Takuma Hirata, Daiki Miyake, Kousuke Koshino, et al. "Tumor Stimulus-Responsive Biodegradable Diblock Copolymer Conjugates as Efficient Anti-Cancer Nanomedicines." Journal of Personalized Medicine 12, no. 5 (April 27, 2022): 698. http://dx.doi.org/10.3390/jpm12050698.

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Biodegradable nanomedicines are widely studied as candidates for the effective treatment of various cancerous diseases. Here, we present the design, synthesis and evaluation of biodegradable polymer-based nanomedicines tailored for tumor-associated stimuli-sensitive drug release and polymer system degradation. Diblock polymer systems were developed, which enabled the release of the carrier drug, pirarubicin, via a pH-sensitive spacer allowing for the restoration of the drug cytotoxicity solely in the tumor tissue. Moreover, the tailored design enables the matrix-metalloproteinases- or reduction-driven degradation of the polymer system into the polymer chains excretable from the body by glomerular filtration. Diblock nanomedicines take advantage of an enhanced EPR effect during the initial phase of nanomedicine pharmacokinetics and should be easily removed from the body after tumor microenvironment-associated biodegradation after fulfilling their role as a drug carrier. In parallel with the similar release profiles of diblock nanomedicine to linear polymer conjugates, these diblock polymer conjugates showed a comparable in vitro cytotoxicity, intracellular uptake, and intratumor penetration properties. More importantly, the diblock nanomedicines showed a remarkable in vivo anti-tumor efficacy, which was far more superior than conventional linear polymer conjugates. These findings suggested the advanced potential of diblock polymer conjugates for anticancer polymer therapeutics.

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20

Kaur, Harmeet, Sapna D. Desai, Virender Kumar, Pooja Rathi, and Jasbir Singh. "Heterocyclic Drug-polymer Conjugates for Cancer Targeted Drug Delivery." Anti-Cancer Agents in Medicinal Chemistry 16, no. 11 (October 3, 2016): 1355–77. http://dx.doi.org/10.2174/1871520615666160504094044.

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21

Kratz, Felix, Ulrich Beyer, and Mark Thomas Schutte. "Drug-Polymer Conjugates Containing Acid-Cleavable Bonds." Critical Reviews in Therapeutic Drug Carrier Systems 16, no. 3 (1999): 245–88. http://dx.doi.org/10.1615/critrevtherdrugcarriersyst.v16.i3.10.

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22

Sanchis, Joaquin, Fabiana Canal, Rut Lucas, and María J. Vicent. "Polymer–drug conjugates for novel molecular targets." Nanomedicine 5, no. 6 (August 2010): 915–35. http://dx.doi.org/10.2217/nnm.10.71.

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23

Yokoyama, Masayuki, Glenn S. Kwon, Teruo Okano, Yasuhisa Sakurai, Takashi Seto, and Kazunori Kataoka. "Preparation of micelle-forming polymer-drug conjugates." Bioconjugate Chemistry 3, no. 4 (July 1992): 295–301. http://dx.doi.org/10.1021/bc00016a007.

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24

Girase, Monika Lotansing, Priyanka Ganeshrao Patil, and Pradum Pundlikrao Ige. "Polymer-drug conjugates as nanomedicine: a review." International Journal of Polymeric Materials and Polymeric Biomaterials 69, no. 15 (September 19, 2019): 990–1014. http://dx.doi.org/10.1080/00914037.2019.1655745.

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25

Khandare, Jayant, and Tamara Minko. "Polymer–drug conjugates: Progress in polymeric prodrugs." Progress in Polymer Science 31, no. 4 (April 2006): 359–97. http://dx.doi.org/10.1016/j.progpolymsci.2005.09.004.

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26

Ke, S., L. Milas, C. Charnsangavej, S. Wallace, and C. Li. "Potentiation of radioresponse by polymer–drug conjugates." Journal of Controlled Release 74, no. 1-3 (July 2001): 237–42. http://dx.doi.org/10.1016/s0168-3659(01)00322-4.

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27

Krakovičová, Hana, Tomáš Etrych, and Karel Ulbrich. "HPMA-based polymer conjugates with drug combination." European Journal of Pharmaceutical Sciences 37, no. 3-4 (June 2009): 405–12. http://dx.doi.org/10.1016/j.ejps.2009.03.011.

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28

Canal, Fabiana, Joaquin Sanchis, and María J. Vicent. "Polymer–drug conjugates as nano-sized medicines." Current Opinion in Biotechnology 22, no. 6 (December 2011): 894–900. http://dx.doi.org/10.1016/j.copbio.2011.06.003.

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29

Duncan, R., and F. Spreafico. "Polymer-drug conjugates: Challenges for phase I." European Journal of Cancer 29 (January 1993): S35. http://dx.doi.org/10.1016/0959-8049(93)90787-g.

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30

Kaur, Loveleen, Ajay Kumar Thakur, Pradeep Kumar, and Inderbir Singh. "Synthesis and characterization of Chitosan-Catechol conjugates: Development and in vitro, in silico and in vivo evaluation of mucoadhesive pellets of lafutidine." Journal of Bioactive and Compatible Polymers 36, no. 2 (March 2021): 139–51. http://dx.doi.org/10.1177/0883911521997849.

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Present study was aimed to synthesize and characterize Chitosan-Catechol conjugates and to design and develop mucoadhesive pellets loaded with lafutidine. SEM images indicated the presence of fibrous structures responsible for enhanced mucoadhesive potential of Chitosan-Catechol conjugates. Thermodynamic stability and amorphous nature of conjugates was confirmed by DSC and XRD studies respectively. Rheological studies were used to evaluate polymer mucin interactions wherein strong interactions between Chitosan-Catechol conjugate and mucin was observed in comparison to pristine chitosan and mucin. The mucoadhesion potential of Chitosan-Catechol (Cht-C) versus Chitosan (Cht) was assessed in silico using molecular mechanics simulations and the results obtained were compared with the in vitro and ex vivo results. Cht-C/mucin demonstrated much higher energy stabilization (∆E ≈ −65 kcal/mol) as compared to Cht/mucin molecular complex. Lafutidine-loaded pellets were prepared from Chitosan (LPC) and Chitosan-Catechol conjugates (LPCC) and were evaluated for various physical properties viz. flow, circularity, roundness, friability, drug content, particle size and percent mucoadhesion. In vitro drug release studies on LPC and LPCC pellets were performed for computing t50%, t90% and mean dissolution time. The values of release exponent from Korsmeyer-Peppas model was reported to be 0.443 and 0.759 for LPC and LPCC pellets suggesting Fickian and non-Fickian mechanism representing drug release, respectively. In vivo results depicted significant controlled release and enhanced residence of the drug after being released from the chitosan-catechol coated pellets. Chitosan-Catechol conjugates were found to be a promising biooadhesive polymer for the development of various mucoadhesive formulations.

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Ulbrich, Karel, Jiří Strohalm, Vladimír Šubr, Dana Plocová, Ruth Duncan, and Blanka Říhová. "Polymeric conjugates of drugs and antibodies for site‐specific drug delivery." Macromolecular Symposia 103, no. 1 (January 1996): 177–92. http://dx.doi.org/10.1002/masy.19961030118.

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AbstractThe synthesis of targetable conjugates of doxorubicin bound to N‐(2‐hydroxypropyl)methacrylamide copolymers was investigated. Anti‐CD3 antibody against TCR/CD3 complex was used to target the conjugates to T‐cells. The effect of structure of the oligopeptide spacer between the drug and polymer as well as of the polymer modification with the antibody on the rate of drug release from the polymeric carrier system incubated in vitro with cathepsin B or with a mixture of intracellular enzymes (tritosomes) is discussed. The results of in vitro drug‐release experiments are correlated with the evaluation of T‐cell cytotoxicity of targeted and nontargeted polymer‐bound doxorubicin conjugates measured in vitro as the inhibition of Con‐A stimulated growth of human peripheral blood lymphocytes (3H‐thymidine incorporation method).

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32

Senevirathne, Suchithra A., Katherine E. Washington, Michael C. Biewer, and Mihaela C. Stefan. "PEG based anti-cancer drug conjugated prodrug micelles for the delivery of anti-cancer agents." Journal of Materials Chemistry B 4, no. 3 (2016): 360–70. http://dx.doi.org/10.1039/c5tb02053k.

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Development of polymer prodrug conjugates has evolved recently in the nano-medicine field for cancer diagnosis and treatment. This review focuses on the development of different types of PEG based polymer drug conjugates used for the delivery of anti-cancer agents.

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Parveen, Shazia, Farukh Arjmand, and Sartaj Tabassum. "Clinical developments of antitumor polymer therapeutics." RSC Advances 9, no. 43 (2019): 24699–721. http://dx.doi.org/10.1039/c9ra04358f.

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Polymer therapeutics encompasses polymer–drug conjugates that are nano-sized, multicomponent constructs already in the clinic as antitumor compounds, either as single agents or in combination with other organic drug scaffolds.

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Duro-Castano, A., J. Movellan, and M. J. Vicent. "Smart branched polymer drug conjugates as nano-sized drug delivery systems." Biomaterials Science 3, no. 10 (2015): 1321–34. http://dx.doi.org/10.1039/c5bm00166h.

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Branched polymers own special properties derived from their intrinsic characteristics. These properties make them ideal candidates to be used as carriers for an improved generation of polymer-drug conjugates.

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Theodosis-Nobelos, Panagiotis, Despina Charalambous, Charalampos Triantis, and Maria Rikkou-Kalourkoti. "Drug Conjugates Using Different Dynamic Covalent Bonds and their Application in Cancer Therapy." Current Drug Delivery 17, no. 7 (September 15, 2020): 542–57. http://dx.doi.org/10.2174/1567201817999200508092141.

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Polymer-drug conjugates are polymers with drug molecules chemically attached to polymer side chains through either a weak (degradable bond) or a dynamic covalent bond. These systems are known as pro-drugs in the inactive form when passing into the blood circulation system. When the prodrug reaches the target organ, tissue or cell, the drug is activated by cleavage of the bond between the drug and polymer, under certain conditions existing in the target organ. The advantages of polymer-drug conjugates compared to other controlled-release carriers and conventional pharmaceutical formulations are the increased drug loading capacity, prolonged <i>in vivo</i> circulation time, enhanced intercellular uptake, better-controlled release, improved therapeutic efficacy, and enhanced permeability and retention effect. The aim of the present review is the investigation of polymer-drug conjugates bearing anti-cancer drugs. The polymer, through its side chains, is linked to the anti-cancer drugs <i>via</i> dynamic covalent bonds, such as hydrazone/imine bonds, disulfide bonds, and boronate esters. These dynamic covalent bonds are cleaved in conditions existing only in cancer cells and not in healthy ones. Thus, ensuring the selective release of drug to the targeted tissue, reducing in this way, the frequent side effects of chemotherapy, leading to a more targeted application, despite the nature of the applied polymer, possessing the ability to aim tumors selectively <i>via</i> incorporation of a relative ligand.

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Kumbhani, Kerul, and Yadavendra Agrawal. "Drug Conjugated Nanomedicine as Prodrug Carrier." Nanoscience & Nanotechnology-Asia 11, no. 6 (July 2013): 86–84. http://dx.doi.org/10.2174/22106812112039990001.

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: It is new approach to combine one or multiple drugs onto the same drug-delivery nanocarrier in accurately controllable manner, by covalently preconjugating one or multiple therapeutic agents by covalent bond to form drug conjugates. It provides the advantages of nano size system with the targeted delivery of drug with great precision. The conjugation system allows the modification in the metabolic path way in the blood stream and can target the delivery to the heart, liver or brain. The cleavable covalent bond allows the therapeutic activity of the individual drugs to be resumed after the drug conjugates are delivered into the target site and get separated from the carriers. The characters of drug conjugated system are (a) a covalent bond between drug and carrier moiety, (b) in vitro cleavage of the bond, (c) optimum release of drug at site of action to ensure effectiveness, (d) no alteration in drug action. As a proof of the concept, synthesis and characterization of stearic acid/oleic acid- diminazene conjugates nanoparticles are demonstrated. It is shown that after conjugation with lipid and/or polymer and synthesized to nanoparticles there is significant improvement in cyctotoxicity and targeted controlled delivery of drug than the free drug.

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Yang, Qiang, Ruogu Qi, Jing Cai, Xiang Kang, Si Sun, Haihua Xiao, Xiabin Jing, Wenliang Li, and Zehua Wang. "Biodegradable polymer–platinum drug conjugates to overcome platinum drug resistance." RSC Advances 5, no. 101 (2015): 83343–49. http://dx.doi.org/10.1039/c5ra11297d.

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Marasini, Nirmal, Shadabul Haque, and Lisa M. Kaminskas. "Polymer-drug conjugates as inhalable drug delivery systems: A review." Current Opinion in Colloid & Interface Science 31 (September 2017): 18–29. http://dx.doi.org/10.1016/j.cocis.2017.06.003.

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Deneka, Alexander Y., Yanis Boumber, Tim Beck, and Erica A. Golemis. "Tumor-Targeted Drug Conjugates as an Emerging Novel Therapeutic Approach in Small Cell Lung Cancer (SCLC)." Cancers 11, no. 9 (September 3, 2019): 1297. http://dx.doi.org/10.3390/cancers11091297.

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There are few effective therapies for small cell lung cancer (SCLC), a highly aggressive disease representing 15% of total lung cancers. With median survival <2 years, SCLC is one of the most lethal cancers. At present, chemotherapies and radiation therapy are commonly used for SCLC management. Few protein-targeted therapies have shown efficacy in improving overall survival; immune checkpoint inhibitors (ICIs) are promising agents, but many SCLC tumors do not express ICI targets such as PD-L1. This article presents an alternative approach to the treatment of SCLC: the use of drug conjugates, where a targeting moiety concentrates otherwise toxic agents in the vicinity of tumors, maximizing the differential between tumor killing and the cytotoxicity of normal tissues. Several tumor-targeted drug conjugate delivery systems exist and are currently being actively tested in the setting of SCLC. These include antibody-drug conjugates (ADCs), radioimmunoconjugates (RICs), small molecule-drug conjugates (SMDCs), and polymer-drug conjugates (PDCs). We summarize the basis of action for these targeting compounds, discussing principles of construction and providing examples of effective versus ineffective compounds, as established by preclinical and clinical testing. Such agents may offer new therapeutic options for the clinical management of this challenging disease in the future.

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Fuhrmann, Gregor, Marc A. Gauthier, and Jean-Christophe Leroux. "Polymer–Enzyme Conjugates for Oral Drug Delivery Applications." CHIMIA International Journal for Chemistry 67, no. 9 (September 18, 2013): 685. http://dx.doi.org/10.2533/chimia.2013.685.

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Singh, Jasbir, Sapna Desai, Snehlata Yadav, Balasubramanian Narasimhan, and Harmeet Kaur. "Polymer Drug Conjugates: Recent Advancements in Various Diseases." Current Pharmaceutical Design 22, no. 19 (May 10, 2016): 2821–43. http://dx.doi.org/10.2174/1381612822666160217125515.

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Greco, Francesca. "Polymer-drug conjugates: current status and future trends." Frontiers in Bioscience 13, no. 13 (2008): 2744. http://dx.doi.org/10.2741/2882.

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Forte, Gianpiero, Isabella Chiarotto, Ilaria Giannicchi, Maria Antonietta Loreto, Andrea Martinelli, Roberta Micci, Federico Pepi, et al. "Characterization of naproxen–polymer conjugates for drug-delivery." Journal of Biomaterials Science, Polymer Edition 27, no. 1 (November 7, 2015): 69–85. http://dx.doi.org/10.1080/09205063.2015.1108637.

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Seifu, Muluneh Fromsa, and Lila Kanta Nath. "Polymer-Drug Conjugates: Novel Carriers for Cancer Chemotherapy." Polymer-Plastics Technology and Materials 58, no. 2 (June 2018): 158–71. http://dx.doi.org/10.1080/03602559.2018.1466172.

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Vicent, Maria J. "Polymer-drug conjugates as modulators of cellular apoptosis." AAPS Journal 9, no. 2 (June 2007): E200—E207. http://dx.doi.org/10.1208/aapsj0902022.

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Rojo, Luis, Mar Fernandez-Gutierrez, Sanjukta Deb, Molly M. Stevens, and Julio San Roman. "Designing dapsone polymer conjugates for controlled drug delivery." Acta Biomaterialia 27 (November 2015): 32–41. http://dx.doi.org/10.1016/j.actbio.2015.08.047.

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Pang, Xin, Yue Jiang, Qicai Xiao, Albert Wingnang Leung, Heyu Hua, and Chuanshan Xu. "pH-responsive polymer–drug conjugates: Design and progress." Journal of Controlled Release 222 (January 2016): 116–29. http://dx.doi.org/10.1016/j.jconrel.2015.12.024.

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Thakor, Pradip, Valamla Bhavana, Reena Sharma, Saurabh Srivastava, Shashi Bala Singh, and Neelesh Kumar Mehra. "Polymer–drug conjugates: recent advances and future perspectives." Drug Discovery Today 25, no. 9 (September 2020): 1718–26. http://dx.doi.org/10.1016/j.drudis.2020.06.028.

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Alven, S., B. A. Aderibigbe, M. O. Balogun, W. M. R. Matshe, and S. S. Ray. "Polymer-drug conjugates containing antimalarial drugs and antibiotics." Journal of Drug Delivery Science and Technology 53 (October 2019): 101171. http://dx.doi.org/10.1016/j.jddst.2019.101171.

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Pang, Xin, Xiaoye Yang, and Guangxi Zhai. "Polymer-drug conjugates: recent progress on administration routes." Expert Opinion on Drug Delivery 11, no. 7 (April 23, 2014): 1075–86. http://dx.doi.org/10.1517/17425247.2014.912779.

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