Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad 500078, Telangana, India.
Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad 500078, Telangana, India.
Int J Pharm. 2019 Feb 10;556:263-275. doi: 10.1016/j.ijpharm.2018.12.022. Epub 2018 Dec 14.
Microneedle-devices provide a promising alternative to syringe-injection-based administration of chemotherapeutics. Dissolvable polymeric microneedles provide possibility of carrying greater payload and dual drugs. Here, we report development of polyvinyl pyrrolidone and polyvinyl alcohol composite dissolvable polymeric microneedle system for co-delivery of doxorubicin HCl and docetaxel. Microneedle patches were characterized using stereomicroscope, scanning electron microscope, texture analyzer and confocal microscope. The greatest amount of doxorubicin and docetaxel loaded within one microneedle patch was 533 ± 65 and 227 ± 23 µg, respectively. Ex-vivo studies in excised murine skin revealed insertion of microneedles and permeation of chemotherapeutics without lag time. Microneedles dissolved within 1 h of insertion in excised skin. Effectiveness of the delivery system was determined in 4T1 breast cancer cells xenografted athymic Balb/c mouse model. Intra-tumoral injection of doxorubicin and doxorubicin + docetaxel combination showed significant toxicity to animals evidenced by drastic reduction in the body weight and 100 percent death within 9-days and after 2-dose administration. Interestingly, doxorubicin and docetaxel administered using microneedles either alone or in combination showed significantly greater survival (100% survival after 16-days and 4-dose administration) compared with intratumoral injections. The normalized body weight, tumor volume and DNA fragmentation assay indicated superior effect of microneedle patch application. Furthermore, co-delivery of doxorubicin and docetaxel, controlled the tumor growth better than the administration of single molecules. Taken together, minimally invasive dissolvable microneedle patch application could compliment painful catheter assisted syringe injections to deliver combination chemotherapeutics.
微针给药系统为基于注射器注射的化疗药物给药提供了一种很有前途的替代方法。可溶解的聚合物微针具有携带更大载药量和双药物的可能性。在这里,我们报告了一种聚乙烯吡咯烷酮和聚乙烯醇复合可溶解聚合物微针系统的开发,用于阿霉素盐酸盐和多西他赛的共递送。使用立体显微镜、扫描电子显微镜、纹理分析仪和共聚焦显微镜对微针贴片进行了表征。每个微针贴片中负载的阿霉素和多西他赛的最大量分别为 533±65 和 227±23µg。在离体鼠皮上的研究表明,微针插入和化疗药物渗透没有滞后时间。在离体皮肤中插入 1 小时内微针溶解。在 4T1 乳腺癌细胞异种移植的无胸腺 Balb/c 小鼠模型中,确定了递药系统的有效性。阿霉素和阿霉素+多西他赛联合瘤内注射对动物有明显的毒性作用,表现为体重急剧下降,9 天内 100%死亡,2 剂给药后。有趣的是,阿霉素和多西他赛单独或联合使用微针给药的生存时间明显更长(16 天和 4 剂给药后 100%存活),与瘤内注射相比。归一化体重、肿瘤体积和 DNA 片段化分析表明微针贴片应用的效果更好。此外,与单一分子给药相比,多西他赛和阿霉素的共递送更好地控制了肿瘤生长。综上所述,微创可溶解微针贴片的应用可以补充疼痛的导管辅助注射器注射,以提供联合化疗药物。
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