4.6 Article

Cross-linked valerolactone copolymer implants with tailorable biodegradation, loading and in vitro release of paclitaxel

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Publisher

ELSEVIER
DOI: 10.1016/j.ejps.2021.105808

Keywords

Paclitaxel (PTX); Polymeric drug delivery; Implant; Degree of swelling; Cross-linking; Loading and release; Degradation

Funding

  1. Natural Sciences and Engineering Research Council of Canada [503143]
  2. Pendant Biosciences Inc. (Toronto, ON)
  3. Pendant Biosciences Inc. (Nashville, TN)
  4. Leslie Dan Faculty of Pharmacy at the University of Toronto

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The study synthesized two novel cross-linkable copolymers for preparing disc-shaped implants, and the manipulation of composition and drug loading conditions was found to influence system performance. The results support further development of cross-linkable matrices for sustained drug delivery.
Implantable drug delivery systems, formed from degradable and non-degradable polymers, can offer several advantages over traditional dosage forms for sustained drug delivery. The majority of degradable implant systems developed to date are composed of poly(lactide-co-glycolide) (PLGA). However, PLGA-based systems are not suitable for the delivery of all drugs. Each drug is unique in terms of physico-chemical properties, and polymer-drug compatibility plays a significant role in determining a drug formulation's performance. In this study, two novel cross-linkable delta-valerolactone-based copolymers were synthesized and used to prepare crosslinked disc-shaped implants. The manipulation of the composition of the discs and conditions used during drug loading were found to influence various aspects of the delivery system performance including the degree of swelling, degradation, drug-loading and in vitro release. The polymeric discs resulted in no adverse effects following subcutaneous implantation in naive rats. These studies support further development of cross-linkable valerolactone matrices as implantable formulations for sustained drug delivery.

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