Preparation and in vitro antitumor effects on MDA-MB-231 cells of niclosamide nanocrystals stabilized by poloxamer188 and PBS.

Abstract

Niclosamide (NLM) has prominent antitumor activities on various kinds of cancer. In this study, we developed a novel niclosamide nanocrystals (NLM-NCs) stabilized by phosphate buffered saline (PBS) and poloxamer188 (P188). The formed NLM-NCs displayed 12,039 times solubility improvement (2.769mg/mL) than that of free NLM and desired storage stability. Transmission electron microscope (TEM) observation illustrated NLM-NCs were needle-like shape. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) analysis indicated that NLM-NCs were not anhydrate or any monohydrate but probable a polymorphic mixture. In vitro release evaluation manifested more than 95% NLM released in 48h from NLM-NCs. In comparison to free NLM, NLM-NCs showed stronger cytotoxic effect on MDA-MB-231 cells and promoted cellular uptake. Wound healing assays indicated that NLM-NCs could inhibit cell migration and also decrease the expression of CD44 which is a marker of breast cancer stem cells. Overall, NLM-NCs were of raised solubility, feasible storage stability and desired killing effect for MDA-MB-231 cell, which revealed the impacts of NLM crystal form on its nanocrystals and provided a novel idea for the design of NLM antineoplastic formulation.