(724b) Long Term Release of Anti-Cancer Drugs Using Double-Wall Microparticles for Breast Carcinoma Treatment

Multidrug resistance (MDR) in tumor cells is one of the major obstacles to successful cancer chemotherapy. MDR happens mainly because of the over-expression of P-glycoprotein (P-gp) that confines the entry of anticancer drugs into cells, affecting treatment outcome. One of the possible solutions to overcome MDR is the controlled delivery of therapeutic drugs at lower concentration and using complementary P-gp inhibitors, concurrently. Double-wall microparticles that can facilitate well-controlled and sustained delivery of anti-cancer agents may offer a new therapeutic approach against MDR in cancerous cells.

This study aims to utilize double-walled microspheres fabricated using coaxial electrohydrodynamic atomization (CEHDA) techniques and loaded with paclitaxel (PTX) as anticancer drug and verapamil (VRP), a P-gp inhibitor, in different core/shell compartments, and to investigate the co-delivery effects of both agents. The second objective is to study the release profile of the above-mentioned drugs loaded in different core/shell phases. Double-wall microparticles of poly (_D,L-lactide) and poly(lactic-co-glycolic acid)  were used to encapsulate the drugs within the core and shell layers. The surface morphology, size, and inner structure of the microspheres were examined using scanning electron microscopy (SEM) and laser scanning confocal microscopy. In vitro drug release was conducted by suspending microspheres in phosphate buffer saline (PBS) solution containing 0.5% v/v Tween 80 over two months. The cytotoxicity effect of different microparticle formulations on MCF7 (human breast carcinoma) cells was determined using a [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)- 2-(4-sulfophenyl)-2H-tetrazolium (MTS) cell viability assay.

The results demonstrated that compared to PTX, the combination therapy of PTX and VRP delivered from double-walled microparticles improves the therapeutic efficacy. In addition, in vitro release tests showed that the system was tuneable for either parallel or sequential release, thereby providing flexibility for desired treatment.