Purpose: Letrozole (LTZ) is effective for the treatment of hormone-receptor-positive breast cancer in postmenopausal women. In this work, and for the first time, using Vibrating Orifice Aerosol Generator (VOAG) technology, we aimed to prepare monodisperse poly-ε-caprolactone (PCL) and poly (D, L-Lactide) (PDLLA) LTZ-loaded microparticles and test their cytotoxicity against cancerous breast cells.
Methods: Plackett-Burman experimental design was utilized to identify the most significant factors affecting particle size distribution to optimize the prepared particles. The generated microparticles were characterized in terms of microscopic morphology, size, drug entrapment efficiency and release profile over one-month period. Long-term cytotoxicity of the microparticles was also investigated using MCF-7 human breast cancer cell lines in comparison with primary mammary epithelial cells (MEC).
Results: The prepared polymeric particles were monodisperse, spherical and apparently smooth, regardless of the polymer used or the loaded LTZ concentration. Particle size varied from 15.6 µm to 91.6 µm and from 22.7 µm to 99.6 µm with size distribution (expressed as span values) ranging from 0.22 to 1.24 and from 0.29 to 1.48 for PCL and PDLLA based microparticles, respectively. Upon optimizing the manufacture parameters, span was reduced to 0.162-0.195. Drug entrapment reached as high as 96.8%, and drug release from PDLLA and PCL followed a biphasic zero-order release using 5% or 30% drug loading in the formulations. Long term in vitro cytotoxicity studies indicated that microparticles formulations significantly and selectively inhibited the growth of MCF-7 cell line over a prolonged period of time but did not elicit any toxic effects on the normal breast epithelial cells.
Conclusion: This study successfully presented a novel approach of adopting a vibrating orifice technology for designing monodisperse polymeric microparticles loaded with LTZ.
Bayan Alemrayat– Pharmaceutics & Polymeric Drug Delivery Research Lab, College of Pharmacy, Qatar University
Mohamed Elrayess– Anti-Doping Lab Qatar, Doha, Qatar
Abdelbary Elhissi– Qatar University