Nanostructured Lipid Carriers to Mediate Brain Delivery of Temazepam: Design and In Vivo Study

The opposing effect of the blood–brain barrier against the delivery of most drugs warrants the need for an efficient brain targeted drug delivery system for the successful management of neurological disorders. Temazepam-loaded nanostructured lipid carriers (NLCs) have shown possibilities for enhancing bioavailability and brain targeting affinity after oral administration. This study aimed to investigate these properties for insomnia treatment. Temazepam-NLCs were prepared by the solvent injection method and optimized using a 4(2) full factorial design. The optimum formulation (NLC-1) consisted of; Compritol(®) 888 ATO (75 mg), oleic acid (25 mg), and Poloxamer(®) 407 (0.3 g), with an entrapment efficiency of 75.2 ± 0.1%. The average size, zeta potential, and polydispersity index were determined to be 306.6 ± 49.6 nm, −10.2 ± 0.3 mV, and 0.09 ± 0.10, respectively. Moreover, an in vitro release study showed that the optimized temazepam NLC-1 formulation had a sustained release profile. Scintigraphy images showed evident improvement in brain uptake for the oral (99m)Tc-temazepam NLC-1 formulation versus the (99m)Tc-temazepam suspension. Pharmacokinetic data revealed a significant increase in the relative bioavailability of (99m)Tc-temazepam NLC-1 formulation (292.7%), compared to that of oral (99m)Tc-temazepam suspension. Besides, the NLC formulation exhibited a distinct targeting affinity to rat brain. In conclusion, our results indicate that the developed temazepam NLC formulation can be considered as a potential nanocarrier for brain-mediated drug delivery in the out-patient management of insomnia.