Zhao Xiaoyu, Zhang Suohui, Yang Guozhong, Zhou Zequan, Gao Yunhua
Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Polymers (Basel). 2020 Jan 1;12(1):59. doi: 10.3390/polym12010059.
Hydrophobic drugs wrapped in poly (lactic-co-glycolic acid) (PLGA)-based microneedles (MNs) require a long time to release completely. To obtain the desired duration, it is still necessary to modulate the release of hydrophobic drugs from MNs, while the PLGA composition is unchangeable. In this work, implantable PLGA microneedles (IPMNs) composed of PLGA arrowheads encapsulating levonorgestrel (LNG) and a water-soluble supporting array were designed. We explored trehalose used as a porogen on the release of hydrophobic LNG from PLGA-based MNs. Varying the trehalose content in PLGA arrowheads could induce different rates of drug release. The highest cumulative release of LNG was 76.2 ± 3.9% for IPMNs with 33.3% trehalose during 21 days in vitro, while the cumulative release of LNG was 60.4 ± 3.5% for IPMNs without trehalose. Pharmacokinetic results in rats showed that plasma levels of LNG were sustained for 13 days for IPMNs with 33.3% trehalose and 16 days for IPMNs without trehalose. Furthermore, the PLGA arrowheads with trehalose degraded more rapidly than those without trehalose over 21 days in rats. Consequently, using trehalose as a porogen was a feasible approach to modulate the release of a hydrophobic drug from PLGA-based MNs.
包裹在聚乳酸-乙醇酸共聚物（PLGA）基微针（MNs）中的疏水性药物需要很长时间才能完全释放。为了获得所需的释放持续时间，在PLGA组成不变的情况下，仍有必要调节疏水性药物从微针中的释放。在这项工作中，设计了由包裹左炔诺孕酮（LNG）的PLGA箭头和水溶性支撑阵列组成的可植入PLGA微针（IPMNs）。我们研究了用作致孔剂的海藻糖对基于PLGA的微针中疏水性LNG释放的影响。改变PLGA箭头中海藻糖的含量可诱导不同的药物释放速率。在体外21天内，含33.3%海藻糖的IPMNs中LNG的最高累积释放率为76.2±3.9%，而不含海藻糖的IPMNs中LNG的累积释放率为60.4±3.5%。大鼠体内药代动力学结果表明，含33.3%海藻糖的IPMNs中LNG的血浆水平维持13天，不含海藻糖的IPMNs中LNG的血浆水平维持16天。此外，在大鼠体内21天内，含海藻糖的PLGA箭头比不含海藻糖的PLGA箭头降解得更快。因此，使用海藻糖作为致孔剂是调节基于PLGA的微针中疏水性药物释放的一种可行方法。
