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

• Published in: Pharmaceutics Vol. 12; no. 5; p. 451
• Main Authors: E Eleraky, Nermin, M Omar, Mahmoud, A Mahmoud, Hemat, A Abou-Taleb, Heba
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14-05-2020; MDPI
• Subjects: Bioavailability; Blood-brain barrier; brain delivery; Drugs; Efficiency; factorial design; Investigations; Laboratory animals; lipid nanoparticles; Lipids; Nanoparticles; nanostructured lipid carriers; Particle size; Variables; United States > US; Egypt; brain delivery; factorial design; lipid nanoparticles; nanostructured lipid carriers
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics12050451

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
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
Tc-temazepam NLC-1 formulation versus the
Tc-temazepam suspension. Pharmacokinetic data revealed a significant increase in the relative bioavailability of
Tc-temazepam NLC-1 formulation (292.7%), compared to that of oral
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.