Design, Formulation and in vivo Evaluation of Novel Honokiol-Loaded PEGylated PLGA Nanocapsules for Treatment of Breast Cancer.

ABSTRACT

BACKGROUND: Honokiol (HK) is a common herbal medicine extracted from magnolia plants. Low aqueous solubility and limited bioavailability of HK have hindered its clinical application, especially for cancer treatment. Nano-drug delivery system has the potential to enhance HK delivery and therefore, enhance its anti-cancer activity. PURPOSE: The study's aim is to design novel PEGylated-PLGA polymeric nanocapsules (NCs) for HK delivery to breast tumor-bearing mice after systemic administration. METHODS: Formulation of different HK-loaded NCs and their physio-chemical characterization were optimized through the use of different formulation variables. The antitumor activity of the HK-loaded NCs was investigated both in vitro using MCF-7 and EAC breast cancer cell lines and in vivo using solid Ehrlich carcinoma (SEC) breast cancer model. RESULTS: The optimum HK-loaded NCs were prepared from 15% PEG-PLGA diblock copolymer and exhibited the lowest nano size of 125 nm, smooth spherical morphology, highest drug loading of 94% and highest cellular uptake into breast cancer cells. HK-loaded PEGylated NCs can effectively inhibit the in vitro cell growth of breast cancer cells by 80.2% and 58.1% compared to 35% and 31% with free HK in the case of MCF-7 and EAC, respectively. HK-loaded NCs inhibited SEC tumor growth by 2.3 fold significantly higher than free HK, in vivo. CONCLUSION: The designed drug delivery system encapsulating HK exhibited a pronounced decrease in tumor growth biomarkers meanwhile proved its safety in animals. Therefore, 15% PEGylated HK-loaded NCs may act as a promising new approach for breast cancer treatment.