In vitro studies of Prednisolone loaded PLGA nanoparticles-surface functionalized with folic acid on glioma and macrophage cell lines

Background: Glucocorticoids are employed for their anti-inflammatory effects in treating glioma, whose cells are known to overexpress the folate receptors. Some glucocorticoids have shown inhibitory effects, but the efficacy of prednisolone when delivered via folate receptor-mediated uptake, has not been attempted. The study aimed to access the efficacy of targeted delivery of prednisolone on glioma cell lines like C6 and U87 via the folate receptors. Methods: Targeted delivery of prednisolone was achieved by initially conjugating folic acid (FA) to the di-block copolymer of polylactic acid (PLA) – polyethylene glycol (PEG). This moiety carrying di-block copolymer was incorporated on the surface of the drug-loaded poly lactic-co-glycolic acid (PLGA) nanoparticle (NP) by employing the Interfacial Activity Assisted Surface Functionalization (IAASF) technique. The NPs were evaluated for size, zeta potential, and drug loading. It was characterized using particle size analyser, SEM, 1H-NMR, and XRD. Cell uptake, cytotoxicity, and anti-inflammatory activities were studied for various formulations. Results: The cytotoxicity assay indicated a high cell growth inhibitory effect of drug encapsulated NPs with FA moiety as compared to free drug and NPs without the moiety for an incubation period of three, five, and six days. The growth-inhibitory effect of the free drug was short-lived, whereas FA functionalized NPs showed higher uptake and sustained inhibitory effect, and were also able to significantly control the release of pro-inflammatory cytokines like tumour necrosis factor-alpha (TNF-α) and nitric oxide (NO). Conclusion: Uptake, attenuation of pro-inflammatory signals, and the inhibitory effect of prednisolone on the cells were more effective when targeted with the FA moiety on the surface of NPs as compared to free drug and NPs without the moiety.