Harnessing Potential of ω-3 Polyunsaturated Fatty Acid with Nanotechnology for Enhanced Breast Cancer Therapy: A Comprehensive Investigation into ALA-Based Liposomal PTX Delivery

Our hypothesis posited that incorporating alpha-linolenic acid (ALA) into liposomes containing
Paclitaxel (PTX) could augment cellular uptake, decrease the therapeutic dosage, and alleviate
PTX-related side effects. Our investigation encompassed characterization of the liposomal
formulation, encompassing aspects like particle size, surface morphology, chemical structure,
drug release kinetics, and stability. Compatibility studies were performed through Fourier
transform infrared spectroscopy (FTIR). By utilizing the Box-Behnken design (BBD), we
developed ALA-based liposomes with satisfactory particle size and entrapment efficiency. It is
noteworthy that ALA incorporation led to a slight increase in particle size but did not notably
affect drug entrapment. In vitro drug release assessments unveiled a sustained release pattern, with ALA-PTX liposomes demonstrating release profiles comparable to PTX liposomes.
Morphological examinations confirmed the spherical structure of the liposomes, indicating that
substituting ALA with phosphatidylcholine did not alter the physicochemical properties. Cellular
uptake investigations showcased enhanced uptake of ALA-based liposomes in contrast to PTX
liposomes, likely attributed to the heightened fluidity conferred by ALA. Efficacy against MCF-7
cells demonstrated concentration-dependent reductions in cell viability, with ALA-PTX liposomes
exhibiting the lowest IC50 value. Morphological analysis confirmed apoptotic changes in cells
treated with all formulations, with ALA-PTX liposomes eliciting more pronounced changes,
indicative of enhanced anticancer efficacy.