Bufton Jack, Jung Sungmin, Evans James C, Bao Zeqing, Aguiar Dean, Allen Christine
Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, ON, M5S 3M2, Canada.
Pendant BioSciences Inc., JLabs Toronto, 661 University Avenue, Suite 1300, Ontario M5G 0B7, Canada.
Eur J Pharm Sci. 2021 Jul 1;162:105808. doi: 10.1016/j.ejps.2021.105808. Epub 2021 Mar 15.
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 δ-valerolactone-based copolymers were synthesized and used to prepare cross-linked 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 naïve rats. These studies support further development of cross-linkable valerolactone matrices as implantable formulations for sustained drug delivery.
由可降解和不可降解聚合物制成的可植入药物递送系统，与传统剂型相比，在持续药物递送方面具有若干优势。迄今为止开发的大多数可降解植入系统由聚（丙交酯-乙交酯）（PLGA）组成。然而，基于PLGA的系统并不适用于所有药物的递送。每种药物在物理化学性质方面都是独特的，聚合物-药物相容性在决定药物制剂的性能方面起着重要作用。在本研究中，合成了两种新型的可交联的基于δ-戊内酯的共聚物，并用于制备交联盘状植入物。发现盘状植入物的组成和载药过程中使用的条件的控制会影响递送系统性能的各个方面，包括溶胀程度、降解、载药和体外释放。在未处理的大鼠皮下植入后，聚合物盘状植入物未产生不良反应。这些研究支持进一步开发可交联的戊内酯基质作为用于持续药物递送的可植入制剂。
