Design of vincristine sulfate loaded poloxamer in situ nanogel: Formulation and in vitro evaluation

Abstract

Vincristine is a naturally occurring anticancer drug with a specific mechanism of action, given intravenously/bolus to treat various types of cancers, including breast cancer. The present studies explored the potential of thermosensitive injectable nanogel of vincristine loaded nanoparticles. In situ gel was chosen as the delivery system because it restricts the unwanted exposure in blood and other healthy tissues, thus eliminate hemolytic side effects of the drug and offer easy administration in vivo. Furthermore, non-biodegradable and cytocompatible polymeric Eudragit RSPO nanoparticles are proposed as ideal candidates for biomedical usage. The method of preparation includes two major steps—the first formation of vincristine nanoparticles with positively charged Eudragit RSPO. In the second step, these nanoparticles were suspended into a thermosensitive gel base to act as an in situ nanogel. Characterization parameters performed are size, surface charge, vincristine sulfate release behavior and mechanism, polymer-drug interaction, and encapsulation efficiency. In situ nanogel was also evaluated for gelling time, drug release, hemocompatibility and cytotoxic activity in breast cancer MCF-7 cell lines. The magnitude of size (<200 nm) and unaltered presence of functional groups after nanoparticle preparation was confirmed by dynamic light scattering technique and FTIR resp. The desirable spherical contour and smooth surface of the prepared nanoparticles were confirmed by scanning electron microscopy. Almost 60% entrapment efficiency was obtained with the optimized batch. In MCF-7 cell lines, the in situ nanogel exhibited dose-dependent cytotoxic activity similar to free drug solution, which indicates incorporating the drug into nanogel does not deteriorate its cytotoxic activity. LD50 for in situ nanogel was 32.3 μg/mL and 12.9 μg/mL for the free drug.Furthermore, VS loaded in situ nanogels possessed less hemolytic activity than the pure drug. Hence, it can be concluded that thermo-receptive in situ nanogel of vincristine can be used to treat breast cancer cells with less hemolytic activity. Further in vivo studies are in progress to establish the effectiveness.