Engineered multifunctional biodegradable hybrid microparticles for paclitaxel delivery in cancer therapy

Abstract

Ovarian cancer is one of the most lethal gynecologic malignancies due to its rapid proliferation, frequent acquisition of chemoresistance, and widespread metastasis within the peritoneal cavity. Intraperitoneal (IP) chemotherapy has demonstrated significant anti-cancer potential but its broad clinical application is hindered by several drug delivery limitations. Herein, we engineer paclitaxel (PTX) laden hybrid microparticles (PTX-Hyb-MPs) for improved delivery of chemotherapy in ovarian cancer. The PTX-Hyb-MPs are comprised of a lipid-coated shell of poly (lactic acid-co-glycolic acid) (PLGA) encapsulating hydrophobic PTX. A co-axial electrohydrodynamic (CEH) process is used for one-step and scalable production of the PTX-Hyb-MP agent with controlled particles size, uniform size distribution, tunable thickness, and high encapsulation rate (92.17 ± 6.9%). The multi-layered structure of the PTX-Hyb-MPs is verified by transmission electron microscopy and confocal fluorescence microscopy. The effect of lipid coating on the enhancement of particle interactions with cancer cells is studied by flow cytometry and confocal fluorescence microscopy. The anti-cancer effect of the PTX-Hyb-MPs is evaluated in SKOV-3 ovarian cancer cells in vitro and a cancer xenograft model in vivo, in comparison with conventional drug delivery methods. Our studies reveal that the PTX-Hyb-MP agent can be potentially used for locoregional treatment of ovarian cancer and other tissue malignancies with sustained drug release, tunable release profiles, enhanced drug uptake, and reduced systemic toxicity.