Research Journal of Pharmacy and Technology

Brain is one of the dominant reservoirs of HIV. Blood Brain Barrier (BBB) provides a great challenge in the delivery of Tenofovir disoproxil fumerate (TDF) to CNS after systemic administration which makes it clinically ineffective. The Intranasal route has a direct passage to the brain bypassing the BBB. So this novel TDF loaded biodegradable NLCs on intranasal administration has the potential to deliver TDF inside the brain in its therapeutic level. TDF is slightly soluble in water (13.4 mg/ml) and pump out by the endothelial layer of BBB. Present work was performed to develop TDF loaded NLCs composed of Compretol 888 ATO and oleic acid. The drug content and entrapment efficiencies were analyzed by UV analysis. The mean diameter of the NLCs was observed to be at 94.7 ± 15.70 nm with PDI of 0.380 ± 0.024 and 134.3 ± 9.71 nm with PDI of 0.358 ± 0.038 respectively for T4 and T5 NLC formulation. The shape of the NLCs were spherical in nature confirmed by TEM and SEM. The zeta potential value of -17.0± 3.87 mV and -17.17 ± 1.05 mV and %EE of 35.5 ± 1.04 % and 34.2 ± 2.78 % were found for T4 and T5 respectively. Stability study reveals the great stability of NLCs in the refrigerated condition and were found to be safe for IN administration as indicated by cytotoxicity study on bEnd.3 cell line and histopathology study on pig nasal mucosa. A sustained release profile of TDF from the NLCs in CSF was observed after in-vitro release study. In vivo pharmacokinetics study on rat plasma and brain implied the rapid availability of NLCs in the brain and gives higher MRT, C_max, and AUC. These data indicate the brain localization and accumulation of NLCs delivering TDF in a sustained manner, which is confirmed by CLSM images of brain cryosections labeled with caumarin-6 NLCs. The results suggest that the developed NLCs have the potential to deliver TDF in the brain for long duration of time for the treatment of Neuro AIDS.