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Objectives: The objective of this work was to enhance the bioavailability of rizatriptan for brain targeted drug delivery through glutathione conjugated liposomes. Methods: Cholesterol glutathione conjugate was synthesized used as a rigidizing agent for liposomes. Liposomes with free cholesterol were also prepared for comparison. 9 batches each were prepared for glutathione conjugated liposomes and non-conjugated liposomes. All formulations were administered to rats. Results: For optimum nonconjugated liposomes batch particle size, drug release and entrapment efficiency were found to be 181nm, 90.2% and 88.1% respectively whereas the same values for glutathione conjugated batch were 194 nm, 84.9% and 86.4% respectively. Zeta potential was between 5 to 19. Polydispersity index was below 0.5. Scanning electron microscopy revealed slightly different shapes for both types of liposomes. These two types of rizatriptan liposomes and marketed oral tablet were administrated to rats to study plasma and brain levels. The tmax for liposomes was faster (1 hr) as compared to the oral tablet. Cmax and AUC values for oral tablet, nonconjugated liposomes and conjugated liposomes were found to be 150.19 ng/ml and 223.99 ng.hr/ml; 320.55 ng/ml and 426.6 ng.hr/ml; 410.12 ng/ ml and 543.49 respectively. Maximum brain levels were achieved by glutathione conjugated liposomes over other liposomes and oral delivery (Cmax 310.46, 135.42 and 79.16 ng.ml respectively; AUC 786.94, 229.55 and 118.11 ng.hr/ml respectively). Drug targeting efficiency for conjugated liposomes was about 5 times higher. Conclusion: The study concluded that glutathione conjugated liposomes of rizatriptan administered by nasal transmucosal route can offer a promising approach to enhance targeted delivery to brain and bioavailability.

Brain Targeted Delivery of Rizatriptan using Glutathione Conjugated Liposomes through Transmucosal Nasal Route