Polymer–drug conjugates: present state of play and future perspectives

Pang, Xin; Du, Hongchuan; Zhang, Hai-Qun; Zhai, Yingjie; Zhai, Guangxi

doi:10.1016/j.drudis.2013.09.007

Cited by 83 publications

(41 citation statements)

References 49 publications

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“…Currently, all of the polymer-drug conjugates that have now entered clinical development are explored on passive targeting, also known as enhanced permeability and retention (EPR) effect [5]. This was a landmark discovery in oncology research, and first proposed by Maeda et al who demonstrated the principle of passive tumor targeting of particles in the 1980s [6].…”

Section: Passive Targeted Polymer-drug Conjugatesmentioning

confidence: 98%

Targeted polymer-drug conjugates: Current progress and future perspective

Yang

et al. 2015

Colloids and Surfaces B: Biointerfaces

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Section: Passive Targeted Polymer-drug Conjugatesmentioning

confidence: 98%

Targeted polymer-drug conjugates: Current progress and future perspective

Yang

et al. 2015

Colloids and Surfaces B: Biointerfaces

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“…A polymer-drug conjugate is an area of polymer therapeutics where the chemotherapeutic agent is not encapsulated but covalently linked to a polymeric macromolecular carrier via biodegradable spacer [3,76,77]. The spacer is usually stable in the systemic circulation but cleaved at the target site in response to specific stimuli, such as temperature, pH, redox potential, light, and enzymes.…”

Section: Chitosan-drug Conjugatesmentioning

confidence: 99%

Recent Advances in Chitosan-Based Nanomedicines for Cancer Chemotherapy

Saneja

Nehate

Alam

et al. 2015

Springer Series on Polymer and Composite Materials

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Chitosan, a cationic polysaccharide, has prompted the continuous impetus for the development of tumor targeted drug delivery systems, thanks to the polymer's biocompatibility, low toxicity, and biodegradability. The presence of primary hydroxyl and amine groups on its backbone allows it for chemical modifications to control its physical properties. The nanomedicines prepared from chitosan and its derivatives can be delivered through different routes, such as oral, intravenous, and intraperitoneal. Chitosan-based nanomedicines including nanoparticles, microspheres, drug conjugates, micelles, hydrogels, etc. are in various stages of development. This polymer is being currently investigated for simultaneous delivery of two chemotherapeutic agents or chemotherapeutic agent with a gene carrier to produce synergistic effects. This chapter summarizes the recent advances in application of chitosan and its derivatives as a carrier for chemotherapeutic agents as well as gene carriers for cancer chemotherapeutics.

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“…PEGylated irinotecan, docetaxel, and SN38 (SN 38, 7-ethyl-10-hydroxy-camptothecin) are under phase II or III clinical trials by the intravenous route for the treatment of solid tumors [22,23]. However, the application of PEGylated chemotherapeutics in lung cancer using pulmonary delivery has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

PEGylation of paclitaxel largely improves its safety and anti-tumor efficacy following pulmonary delivery in a mouse model of lung carcinoma

Luo

Loira-Pastoriza

Patil

et al. 2016

Journal of Controlled Release

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The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. AbstractPulmonary delivery offers an attractive route of administration for chemotherapeutic agents, with the advantages of high drug concentrations locally and low side effects systemically. However, fast clearance mechanisms result in short residence time of small molecule drugs in the lungs. Moreover, the local toxicity induced by antineoplastic drugs is considered a major obstacle for the clinical application of inhaled chemotherapy. In this study, we explored the utility of 6 kDa and 20 kDa polyethylene glycol-paclitaxel (PEG-PTX) conjugates to retain paclitaxel within the lungs, achieve its sustained release locally, and thereby, improve its efficacy and reduce its pulmonary toxicity. The conjugates increased the maximum tolerated dose of paclitaxel by up to 100-fold following intratracheal instillation in healthy mice. PEG-PTX conjugates induced lung inflammation. However, the inflammation was lower than that induced by an equivalent dose of the free drug and it was reversible. Conjugation of paclitaxel to both PEG sizes significantly enhanced its anti-tumor efficacy following intratracheal instillation of a single dose in a Lewis lung carcinoma model in mice. PEG-PTX 20k showed equivalent efficacy as PEG-PTX 6k delivered at a 2.5-fold higher dose, suggesting that the molecular weight of the conjugate plays a role in anti-cancer activity. PEG-PTX 20k conjugate presented a prolonged residency and a sustained paclitaxel release within the lungs. This study showed that PEGylation of paclitaxel offers a potential delivery system for inhalation with improved anti-cancer efficacy, prolonged exposure of lung-resident tumors to the antineoplastic drug and reduced local toxicity.

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Polymer–drug conjugates: present state of play and future perspectives

Cited by 83 publications

References 49 publications

Targeted polymer-drug conjugates: Current progress and future perspective

Targeted polymer-drug conjugates: Current progress and future perspective

Recent Advances in Chitosan-Based Nanomedicines for Cancer Chemotherapy

PEGylation of paclitaxel largely improves its safety and anti-tumor efficacy following pulmonary delivery in a mouse model of lung carcinoma

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