Delivery of Entrapped Loperamide in Polysorbate 80 Coated Liposomes to Brain for its Antinociceptive Activity Through Central Opiate Receptors

The delivery of drugs to the brain is often impeded by the blood-brain barrier (BBB), posing a significant challenge for therapeutic interventions targeting central nervous system (CNS) disorders. This study investigates the potential of encapsulating Loperamide within Polysorbate 80-coated nanosized liposomes to facilitate its transport across the BBB. The antinociceptive efficacy of these liposomes was evaluated in vivo. The formulation process involved coating Loperamide-loaded liposomes with 1% Polysorbate 80 using the reverse phase evaporation technique. Characterization of the liposomes was conducted using zetasizer analysis, revealing a mean particle diameter of 79.21±3.85 nm, indicative of enhanced permeability through the BBB relative to uncoated liposomes, which measured 146.15±2.65 nm. The zeta potential of the coated and uncoated formulations was -26.4 mV and -16.6 mV, respectively, while the polydispersity index demonstrated a more uniform size distribution for the coated liposomes (0.21) compared to uncoated ones (1.15). Transmission electron microscopy confirmed the presence of nanosized vesicles in the formulation. Animal studies using Wistar rats showed a significant increase in analgesic activity for the coated liposomes, with notable improvements observed in both the Eddy hot plate and tail flick tests. Brain quantification studies further confirmed the successful delivery of Loperamide to the brain in the coated formulation. These findings suggest that Polysorbate 80-coated liposomes are an effective carrier for Loperamide, facilitating its penetration across the BBB and subsequent CNS activity.