Department of Chemistry, University of Liverpool, Crown Street, Liverpool, L69 7ZD, UK.
Materials Innovation Factory, University of Liverpool, Crown Street, L69 7ZD, UK.
J Mater Chem B. 2022 Jun 15;10(23):4395-4404. doi: 10.1039/d2tb00825d.
Long-acting drug delivery is a growing area of interest as it overcomes many challenges related to patient adherence to therapy and the pill burden associated with chronic illness. Injectable formulations are becoming more common and drug-releasing implants also provide several opportunities. Highly water soluble drug compounds are poor candidates for long-acting delivery. Here, the water-soluble nucleoside reverse transcriptase inhibitor emtricitabine (FTC) has been used as a novel A-B monomer in step-growth polymerisation with chloroformate functional C monomers, to produce new poly(carbamate/carbonate) structures with varying architecture. The polymer prodrugs were all solid at ambient temperature and have been shown to release FTC when subjected to mixed gender human plasma. Vacuum compression moulding has been used to form solid rod implants without polymer degradation; the rods show FTC release over long periods in the presence of microsomes, establishing the basis of a polymer prodrug strategy for FTC delivery.
长效药物递送是一个日益受到关注的领域，因为它克服了许多与患者对治疗的依从性以及与慢性病相关的药物负担相关的挑战。注射制剂变得越来越普遍，药物释放植入物也提供了许多机会。高度水溶性药物化合物不适合长效递送。在这里，水溶性核苷逆转录酶抑制剂恩曲他滨（FTC）已被用作逐步增长聚合中的新型 A-B 单体，与氯甲酸酯功能 C 单体一起生产具有不同结构的新型聚（碳酸酯/氨基甲酸酯）结构。聚合物前药在环境温度下均为固体，并且当暴露于混合性别人血浆时已显示出 FTC 的释放。真空压缩成型已用于形成无聚合物降解的固体棒状植入物；在微粒体存在的情况下，这些棒状植入物显示出 FTC 的长期释放，为 FTC 递药的聚合物前药策略奠定了基础。
