Department of Pharmaceutics, Dr. Prabhakar B Kore Basic Science Research Center, Off-campus, KLE College of Pharmacy (A constituent unit of KAHER-Belagavi), Rajajinagar, Bengaluru 560010 Karnataka, India.
Mol Pharm. 2023 Oct 2;20(10):5006-5018. doi: 10.1021/acs.molpharmaceut.3c00288. Epub 2023 Sep 1.
Tenofovir disoproxil fumarate (TDF)-loaded bioadhesive chitosan microparticles (CM) were developed by an emulsification internal gelation technique. Among different batches produced, ECH-4 was found to display a high % entrapment efficiency (68.93 ± 1.76%) and sustained drug release of 88.05 ± 0.38% at 24 h. Solid state characterization of ECH-4 employing DSC and PXRD indicated that the TDF existed in an amorphous state as a solid-solid solution in chitosan. Scanning electron microscopy revealed CM of ECH-4 was spherical in shape with a rough surface topography. Laser scattering analysis using Malvern Master sizer indicated that particle size of ECH-4 was in the range of 0.52 ± 0.10 μm to 284.79 ± 21.42 μm with a surface-mean diameter of 12.41 ± 0.06 μm. mucoadhesion studies using rabbit mucosa as a substrate indicated that 10.34 ± 2.08% of CM of ECH-4 was retained at the end of 24 h. The microparticles of ECH-4 were incorporated into dispersible tablets (DT-TCM) intended for intravaginal administration, in view to arrest the pre-exposure transmission of HIV during sexual intercourse. release from the dispersible tablet (F3) into simulated vaginal fluid (pH 4.5) displayed a sustained release profile of TDF as 89.98 ± 1.61% of TDF was released at 24 h. The dissolution profile of the DT-TCM was found to be similar to that of TDF loaded CM with the values of (difference factor) and (similarity factor) being 1.52 and 78.02, respectively. Therefore, DT-TCM would be a promising novel drug delivery platform for pre-exposure prophylaxis against HIV.
富马酸替诺福韦二吡呋酯（TDF）负载的生物黏附性壳聚糖微球（CM）通过乳化-内凝胶技术制备。在不同批次的产物中，ECH-4 显示出高的 %包封效率（68.93±1.76%）和 24 小时内 88.05±0.38%的持续药物释放。采用 DSC 和 PXRD 对 ECH-4 的固态特性进行表征表明，TDF 以无定形状态作为壳聚糖中的固-固溶液存在。扫描电子显微镜显示 ECH-4 的 CM 呈球形，表面形貌粗糙。使用 Malvern Master sizer 的激光散射分析表明，ECH-4 的粒径范围为 0.52±0.10 μm 至 284.79±21.42 μm，表面平均直径为 12.41±0.06 μm。使用兔黏膜作为基质的黏膜黏附研究表明，在 24 小时结束时，ECH-4 的 CM 中有 10.34±2.08%保留。将 ECH-4 的微球掺入用于阴道内给药的分散片（DT-TCM）中，以期在性交过程中阻止 HIV 的预先暴露传播。从分散片（F3）释放到模拟阴道液（pH 4.5）中，TDF 呈现出持续释放的特征，24 小时内释放了 89.98±1.61%的 TDF。DT-TCM 的溶解曲线与负载 TDF 的 CM 相似，（差异因子）和（相似因子）的值分别为 1.52 和 78.02。因此，DT-TCM 将是一种有前途的用于 HIV 预先暴露预防的新型药物传递平台。
