Dipartimento di Chimica e Tecnologia del Farmaco, University of Perugia, Perugia, Italy.
AAPS PharmSciTech. 2010 Mar;11(1):212-20. doi: 10.1208/s12249-009-9361-8. Epub 2010 Feb 2.
The aim of this work was the formulation and characterization of alginate (ALG)-doxycycline (DOX) hydrogel microparticles (MPs) embedded into Pluronic F127 thermogel for DOX intradermal sustained delivery. ALG-DOX MPs were formed by adding a solution of the drug into a 1.5% polymer solution while stirring. The MPs were cross-linked by dispersion into a 1.2% CaCl2 solution. Free MPs were characterized in terms of size, drug content, and release behavior by HPLC and UV-vis. DOX and hydrogel MPs were embedded into PF127, PF127-HPMC, and PF127-Methocel thermogels. The thermogels were characterized in terms of gelling time, morphology, and release behavior. A target release period of 4-7 days was considered optimal. The hydrogel MPs were about 20 microm in size with 90% of the population <59 microm. Drug content was about 35% (w/w). DOX released rapidly from the MPs, 90% within 2 days. An expected faster release was observed for free DOX from the thermogels with 80-90% of drug released after 3.5-4 h even in the presence of 1% HPMC or Methocel. The release was sustained after embedding the MPs into PF127 and PF127-HPMC thermogels. In particular, the PF127-HPMC thermogel showed an almost linear release, reaching 80% after 3 days and 90% up to 6 days. Although a further characterization and formulation assessment is required to optimize MP characteristics, ALG/DOX-loaded hydrogel MPs, when embedded into a PF127-HPMC thermogel, show a potential for achieving a 7-day sustained release formulation for DOX intradermal delivery.
本工作的目的是制备并表征藻酸盐（ALG）-盐酸多西环素（DOX）水凝胶微球（MPs），并将其嵌入泊洛沙姆 F127（Pluronic F127）温敏凝胶中，以实现 DOX 的皮内持续释放。ALG-DOX MPs 通过将药物溶液加入到 1.5%聚合物溶液中同时搅拌形成。MPs 通过分散到 1.2%氯化钙溶液中进行交联。通过 HPLC 和 UV-vis 对游离 MPs 的粒径、药物含量和释放行为进行了表征。将 DOX 和水凝胶 MPs 嵌入到泊洛沙姆 F127、泊洛沙姆 F127-羟丙甲纤维素（HPMC）和泊洛沙姆 F127-甲基纤维素（Methocel）温敏凝胶中。对温敏凝胶的胶凝时间、形态和释放行为进行了表征。考虑将 4-7 天的目标释放期作为最佳释放期。水凝胶 MPs 的粒径约为 20 微米，其中 90%的粒径小于 59 微米。药物含量约为 35%（w/w）。DOX 从 MPs 中快速释放，2 天内释放 90%。即使存在 1%的 HPMC 或 Methocel，游离 DOX 从温敏凝胶中的释放速度也更快，80-90%的药物在 3.5-4 小时内释放。将 MPs 嵌入到泊洛沙姆 F127 和泊洛沙姆 F127-HPMC 温敏凝胶中后，释放得到了持续。特别是，泊洛沙姆 F127-HPMC 温敏凝胶表现出几乎线性的释放，3 天后达到 80%，6 天后达到 90%。虽然还需要进一步的特征描述和配方评估来优化 MPs 的特性，但负载 ALG/DOX 的水凝胶 MPs 嵌入泊洛沙姆 F127-HPMC 温敏凝胶后，有望实现 DOX 皮内持续释放 7 天的配方。
