Polymer-prodrug conjugates as candidates for degradable, long-acting implants, releasing the water-soluble nucleoside reverse-transcriptase inhibitor emtricitabine.
Polymer-prodrug conjugates as candidates for degradable, long-acting implants, releasing the water-soluble nucleoside reverse-transcriptase inhibitor emtricitabine.
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聚合物-前药偶联物作为可降解，长效植入物的候选物，释放水溶性核苷逆转录酶抑制剂恩曲他滨。
DOI：
10.1039/d3tb02268d
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发表时间：
2023-12-13
期刊：
影响因子：
--
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多年来，循环的可溶性聚合物-药物缀合物已被用于帮助递送敏感的、难溶性的或细胞毒性的药物，延长循环时间或使副作用最小化。长效治疗剂在医疗保健方面的重要性日益增加，其中液体制剂的肌内和皮下给药是最常见的。可降解的植入物也提供了机会，并且聚合物-前药缀合物作为植入物材料的用途在这方面尚未被广泛报道。在这里，水溶性核苷逆转录酶抑制剂恩曲他滨（FTC）的聚合物-前药缀合物的潜力进行了研究。一种新的二醇单体支架，允许前药取代的变化，已被用于形成聚酯和聚碳酸酯的逐步增长聚合。已经筛选了能够形成植入物的材料的物理性质，研究了药物释放以提供机制见解，并且已经证明了在相关生理条件下至少两周的时间内FTC的可调延长释放。恩曲他滨已被修饰以形成一系列用于侧链聚合物-前药缀合物合成的二醇单体。筛选已经确定了能够通过酶裂解机制释放母体药物的植入物形成结构。
Circulating, soluble polymer–drug conjugates have been utilised for many years to aid the delivery of sensitive, poorly-soluble or cytotoxic drugs, prolong circulation times or minimise side effects. Long-acting therapeutics are increasing in their healthcare importance, with intramuscular and subcutaneous administration of liquid formulations being most common. Degradable implants also offer opportunities and the use of polymer–prodrug conjugates as implant materials has not been widely reported in this context. Here, the potential for polymer–prodrug conjugates of the water soluble nucleoside reverse transciption inhibitor emtricitabine (FTC) is studied. A novel diol monomer scaffold, allowing variation of prodrug substitution, has been used to form polyesters and polycarbonates by step-growth polymerisation. Materials have been screened for physical properties that enable implant formation, studied for drug release to provide mechanistic insights, and tunable prolonged release of FTC has been demonstrated over a period of at least two weeks under relevant physiological conditions. Emtricitabine, has been modified to form a series of diol monomers for pendant polymer–prodrug conjugate synthesis. Screening has identified structures for implant formation able to release parent drug via enzymatic cleavage mechanisms.
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影响因子：
2.8
作者：
Wisniewska-Jarosinska M;Sliwinski T;Kasznicki J;Kaczmarczyk D;Krupa R;Bloch K;Drzewoski J;Chojnacki J;Blasiak J;Morawiec-Sztandera A
通讯作者：
Morawiec-Sztandera A
影响因子：
2.3
作者：
Nasiri, Muhammad Iqbal;Yousuf, Rabia Ismail;Anwer, Sohail
通讯作者：
Anwer, Sohail
DOI：
10.1039/d2tb00825d
发表时间：
2022-06-15
期刊：
Journal of materials chemistry. B
影响因子：
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作者：
通讯作者：
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影响因子：
1.8
作者：
Dong, Kesu;Sugita-Konishi, Yoshiko;Kumagai, Susumu
通讯作者：
Kumagai, Susumu
DOI：
10.1021/6010062o
发表时间：
2002-03-01
期刊：
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
影响因子：
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作者：
Mattioni, BE;Jurs, PC
通讯作者：
Jurs, PC