Abstract
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 42 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 99mTc-temazepam NLC-1 formulation versus the 99mTc-temazepam suspension. Pharmacokinetic data revealed a significant increase in the relative bioavailability of 99mTc-temazepam NLC-1 formulation (292.7%), compared to that of oral 99mTc-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.
Highlights
The blood-brain barrier (BBB) has a preventive effect against the permeation of most therapeutics across the brain, limiting the effective management of most neurological diseases [1]
It was hypothesized that nanostructured lipid carriers (NLCs) containing high temazepam content are transported across the intestinal mucosa, thereby significantly increasing the fraction absorbed
The models generated for the significant factors are capable of identifying how they influence the critical quality attributes (CQAs) of the formulations, as well as identifying the interactions between the factors that allow the system to be optimized effectively
Summary
The blood-brain barrier (BBB) has a preventive effect against the permeation of most therapeutics across the brain, limiting the effective management of most neurological diseases [1]. The restrictive nature of BBB is due to its complex structure, which includes several cells (endothelial cells, perivascular mast cells, pericytes, and astroglia). The tightness of the BBB inhibits the paracellular transport of most drugs [2,3,4]. The therapeutic targeting of the brain will, add numerous benefits through a rational approach. Temazepam (7-chloro-3-hydroxy-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one), (Figure 1), is a gamma-aminobutyric acid (GABA) modulator. It is widely used clinically because of its Temazepam (7-chloro-3-hydroxy-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one), (Figure 1), is a gamma-aminobutyric acid (GABA) modulator It is widely used clinically because of its anxiolytic, asendxaiotilvytei,c,asnedataivneti,caonndvaunlstaicnotnveufflescatnst e[ff5–e7ct]s.
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