DESIGN, OPTIMIZATION AND IN SILICO STUDIES OF FOLIC ACID-CONJUGATED DOCETAXEL-LOADED LIPOSOMES FOR TARGETED DELIVERY TO A549 LUNG ADENOCARCINOMA CELLS
DOI:
https://doi.org/10.22159/ijap.2026v18i2.57010Keywords:
Docetaxel, Liposome, A549 lung adenocarcinoma cells, Folic acid, NHSAbstract
Objective: This study aimed to develop and optimize a folic acid-conjugated liposomal formulation of docetaxel (FA-Opt-DTXL) for enhanced delivery and cytotoxic efficacy against folate receptor–overexpressing A549 lung adenocarcinoma cells.
Methods: A Box–Behnken design (BBD) coupled with response surface methodology was employed to optimize critical formulation parameter soya lecithin quantity, cholesterol content, and sonication time, affecting liposomal characteristics. The optimized docetaxel-loaded liposomes (Opt-DTXL) were characterized for particle size, entrapment efficiency, and zeta potential. FA–PEG–Cholesterol conjugate was synthesized via NHS-activated ester coupling and incorporated into preformed liposomes using the post-insertion method to yield FA-Opt-DTXL. Morphological analysis was performed using TEM, and cytotoxicity was assessed via IC₅₀ determination and fluorescence-based apoptosis assays.
Results: The optimized Opt-DTXL formulation exhibited a particle size of 239.60 nm, entrapment efficiency of 84.03%, and zeta potential of –22.85 mV, closely matching predicted values. TEM imaging confirmed spherical, well-defined vesicles. Compared to Pure-DXT and Opt-DTXL, FA-Opt-DTXL demonstrated superior cytotoxicity, with an IC₅₀ of 16.67 µg/ml. Apoptotic assays revealed dominant red fluorescence and chromatin fragmentation in FA-Opt-DTXL–treated cells, indicating enhanced receptor-mediated uptake and intracellular drug accumulation. The integration of statistical optimization and Network pharmacology and folate-targeted surface modification yielded a potent nanocarrier system with improved cytotoxicity against A549 lung adenocarcinoma cells.
Conclusion: FA-Opt-DTXL represents a promising platform for site-specific docetaxel delivery in folate receptor–positive malignancies, offering translational potential for targeted cancer therapy, also supported by network pharmacology and molecular docking studies.
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