Development of poly (lactic-Co-glycolic acid) nanoparticles of retinol using supercritical fluid technology: Factorial design-based optimization, physicochemical characterization and cell viability assessment

Retinol acetate (RA) has potential antineoplastic and chemo-preventive activities. However, RA is highly hydrophobic, which decreases its bioavailability and limits its therapeutic potential. Therefore, this study aimed to develop and characterize poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) using supercritical fluid technology (SFT). Additionally, the therapeutic effectiveness of RA-loaded PLGA-NPs was evaluated using cytotoxicity assay. In the present investigation, we have explored novel, green technology for preparing PLGA-NPs, which is the modified rapid expansion of supercritical solution (RESS) with mixing and sonication. Preoptimization feasibility studies were taken into consideration when choosing dependent and independent factors. 2³ full factorial design was applied to quantify the effect of dependent factors on independent factors. The optimized RA-loaded PLGA-NPs formulation was characterized by various parameters. The average particle size, polydispersity index, and zeta potential of optimized PLGA-NPs were 100.8 ± 10 nm, 0.412 ± 0.08, and −17.6 mV, respectively. The drug content was observed to be 82 ± 5 % and % entrapment efficiency was found to be 99.6 ± 0.32 %. The XRD and DSC of NPs showed that the drug is in a non-crystalline state. FTIR spectroscopy confirmed the effective incorporation of RA into the PLGA-NPs. SEM and TEM studies exhibit uniform-shaped particles of 70–100 nm size. The release of the drug from RA-PLGA nanoparticles was regulated by the initial diffusion of RA and later by the degradation of the biodegradable polymer. MTT assay revealed that the RA-loaded PLGA-NPs were superior in arresting cell growth as compared to free RA. In summary, RA-encapsulated PLGA-NPs, prepared by the SFT, have great potential as a drug delivery system for clinical applications in anti-cancer treatment.