The key objective of the current research was to fabricate and optimize Capecitabine (Cap)-loaded [poly(lactic-co-glycolic acid)] PLGA-based nanoparticles (NPs) by enabling quality by design (QbD) approach for enhancing antitumor activity by promising delivery of the drug at the colonic site. The current research was based on fabricating PLGA-based nanoparticles along with Eudragit S100 as enteric polymer employing solvent shifting method followed by optimization using QbD approach. This approach was found to be useful for understanding the multiple factors and their interaction influencing the product by utilizing Design of Experiment (DOE). Box-Behnken design (BBD) was adopted to achieve the required critical quality attributes (CQAs), i.e., minimizing particle size, maximizing entrapment efficiency, and minimizing PDI value. The optimized nanoparticles were lyophilized and characterized by FT-IR, DSC, TEM, DLS, MTT assay using HT-29 cell lines, and in vivo pharmacokinetic studies. The optimized PLGA-based nanoparticles were found to possess average particle size, PDI, zeta potential, and entrapment efficiency of 195 nm, 0.214, -6.65 mV, and 65%, respectively. TEM analysis revealed the spherical nature of nanoparticles. The FT-IR and DSC studies revealed no interaction. The bioavailability of Cap-loaded nanoparticles was found to be two fold increased than the pure drug, and also, it exhibited significantly more cytotoxic to tumor cells as compared to pure drug as confirmed by MTT assay. The optimized PLGA-based nanoparticles found to possess enhanced bioavailability and significantly more cytotoxic potential as compared to pure drug.
Keywords: Capecitabine; Cytotoxic potential; DoE; MTT assay; PLGA; Quality by design (QbD).
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