Dissolvable microneedle patch containing doxorubicin and docetaxel is effective in 4T1 xenografted breast cancer mouse model

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 mu g, 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.