Enhanced cytotoxicity of docetaxel delivered through folic acid grafted poloxamer P188 polymeric micelles

Year 2025, Volume: 29 Issue: 5, 2126 - 2142, 01.09.2025

Amol Tatode Divya Zambre Mohammad Qutub Tanvi Premchandani Milind Umekar Prashant Pande

https://doi.org/10.12991/jrespharm.1766361

Abstract

Nanotechnology-based drug delivery systems have gained significant attention for improving cancer treatment. In this study, folic acid (FA)-conjugated Poloxamer P188 (FA-P188) micelles were developed for targeted delivery of docetaxel (DTX) to cancer cells that overexpress folate receptors. The micelles were prepared using the thin- film hydration method, where polymers and DTX were dissolved in an organic solvent, followed by solvent evaporation to form a thin film, which was then hydrated with water to form micelles. The critical micelle concentration (CMC) was determined using UV spectroscopy with an iodine standard solution. Micelle size, polydispersity index (PDI), and surface charge were characterized using dynamic light scattering, and the morphology was visualized through scanning electron microscopy. Entrapment efficiency of DTX in micelles was quantified using ultracentrifugation and UV spectrophotometry, after separating the unencapsulated drug. In vitro drug release kinetics were assessed via dialysis and UV spectroscopy. Hemocompatibility was tested by measuring hemoglobin release from red blood cells using spectrophotometry. The anticancer efficacy of the DTX formulations was evaluated in MDA-MB-231 breast cancer cells using the MTT assay after a 72-hour exposure. Stability of the FA-P188-DTX micelles was assessed under accelerated conditions (40°C, 75% relative humidity) for three months. The study's findings showed successful conjugation of FA to P188 and effective encapsulation of DTX in FA-P188 micelles. The optimized FA-P188-DTX micelles demonstrated particle sizes smaller than 200 nm, a PDI of less than 0.2, and a drug entrapment efficiency exceeding 75%. In vitro cytotoxicity assays showed enhanced cytotoxicity of FA-P188-DTX micelles in MDA-MB-231 cancer cells compared to DTX alone and non-targeted micelles. These results highlight the targeting capability and sustained drug release properties of FA-P188-DTX micelles, suggesting their promising potential for targeted cancer therapy involving docetaxel.

Keywords

Docetaxel , targeted drug delivery , polymeric micelles , folic acid , cancer therapy

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