Development And Evaluation Of Folate Conjugated Nanostructured Lipid Carriers Of Emtricitabine For Targeted Brain Therapy

ABSTRACTBackground: Delivery of antiretroviral drugs to the central nervous system is challengingbecause of the restrictive blood–brain barrier. Nanostructured lipid carriers (NLCs) provide alipid-based platform for drug incorporation, controlled release and surface functionalization. Thepresent study aimed to develop folate-conjugated NLCs of emtricitabine as a potential braintargeted delivery system. Methods: Emtricitabine was screened for solubility in selected solidand liquid lipids. A UV spectrophotometric method was established at 281 nm. Nine NLCformulations were prepared using glyceryl monostearate (GMS), oleic acid, Poloxamer 188 andsoya lecithin. The formulations were evaluated for entrapment efficiency and in vitro drugrelease, and the optimized formulation was surface-functionalized with folic acid usingcarbodiimide chemistry. The optimized folate-conjugated NLC was characterized by FTIR,SEM, dynamic light scattering, zeta potential and short-term stability testing. Results: GMS andoleic acid showed the highest apparent solubilization among the screened solid and liquid lipids,respectively. The optimized precursor formulation was F8, containing 100 mg emtricitabine, 650mg GMS, 150 mg oleic acid, 300 mg Poloxamer 188 and 50 mg soya lecithin. F8 showed 89.46± 1.02% entrapment efficiency and 91.17 ± 1.28% cumulative drug release at 24 h. After folateconjugation, the optimized system exhibited a Z-average particle size of 86.7 nm, PDI of 0.218and zeta potential of -34.0 mV. SEM showed predominantly spherical to nearly sphericalnanoparticles. At 4 ± 2°C for 30 days, particle size was 88.3 ± 2.0 nm, PDI 0.225 ± 0.011, drugremaining 98.87 ± 0.51% and entrapment efficiency 88.62 ± 1.09%. Conclusion: The developedfolate-conjugated emtricitabine NLC showed favorable nanoscale characteristics, high drugentrapment, prolonged release and short-term physical stability. The findings support furtherbiological investigation; however, brain targeting, BBB transport and therapeutic superioritywere not established by the present formulation study and require dedicated in vitro and in vivoevaluation.