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 enhanci...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-05-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/12/5/451 |
| _version_ | 1797568038951714816 |
|---|---|
| author | Nermin E. Eleraky Mahmoud M. Omar Hemat A. Mahmoud Heba A. Abou-Taleb |
| author_facet | Nermin E. Eleraky Mahmoud M. Omar Hemat A. Mahmoud Heba A. Abou-Taleb |
| author_sort | Nermin E. Eleraky |
| collection | DOAJ |
| description | 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<sup>2</sup> full factorial design. The optimum formulation (NLC-1) consisted of; Compritol<sup>®</sup> 888 ATO (75 mg), oleic acid (25 mg), and Poloxamer<sup>®</sup> 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 <sup>99m</sup>Tc-temazepam NLC-1 formulation versus the <sup>99m</sup>Tc-temazepam suspension. Pharmacokinetic data revealed a significant increase in the relative bioavailability of <sup>99m</sup>Tc-temazepam NLC-1 formulation (292.7%), compared to that of oral <sup>99m</sup>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. |
| first_indexed | 2024-03-10T19:50:41Z |
| format | Article |
| id | doaj.art-7d1c72507d5940448489d6bf1ba85146 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T19:50:41Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-7d1c72507d5940448489d6bf1ba851462023-11-20T00:24:22ZengMDPI AGPharmaceutics1999-49232020-05-0112545110.3390/pharmaceutics12050451Nanostructured Lipid Carriers to Mediate Brain Delivery of Temazepam: Design and In Vivo StudyNermin E. Eleraky0Mahmoud M. Omar1Hemat A. Mahmoud2Heba A. Abou-Taleb3Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Deraya University, Minia 61768, EgyptDepartment of Clinical Oncology and Nuclear Medicine, Assiut University, Assiut 71526, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Nahda University (NUB), Beni-Suef 62511, EgyptThe 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<sup>2</sup> full factorial design. The optimum formulation (NLC-1) consisted of; Compritol<sup>®</sup> 888 ATO (75 mg), oleic acid (25 mg), and Poloxamer<sup>®</sup> 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 <sup>99m</sup>Tc-temazepam NLC-1 formulation versus the <sup>99m</sup>Tc-temazepam suspension. Pharmacokinetic data revealed a significant increase in the relative bioavailability of <sup>99m</sup>Tc-temazepam NLC-1 formulation (292.7%), compared to that of oral <sup>99m</sup>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.https://www.mdpi.com/1999-4923/12/5/451lipid nanoparticlesbrain deliverynanostructured lipid carriersfactorial design |
| spellingShingle | Nermin E. Eleraky Mahmoud M. Omar Hemat A. Mahmoud Heba A. Abou-Taleb Nanostructured Lipid Carriers to Mediate Brain Delivery of Temazepam: Design and In Vivo Study Pharmaceutics lipid nanoparticles brain delivery nanostructured lipid carriers factorial design |
| title | Nanostructured Lipid Carriers to Mediate Brain Delivery of Temazepam: Design and In Vivo Study |
| title_full | Nanostructured Lipid Carriers to Mediate Brain Delivery of Temazepam: Design and In Vivo Study |
| title_fullStr | Nanostructured Lipid Carriers to Mediate Brain Delivery of Temazepam: Design and In Vivo Study |
| title_full_unstemmed | Nanostructured Lipid Carriers to Mediate Brain Delivery of Temazepam: Design and In Vivo Study |
| title_short | Nanostructured Lipid Carriers to Mediate Brain Delivery of Temazepam: Design and In Vivo Study |
| title_sort | nanostructured lipid carriers to mediate brain delivery of temazepam design and in vivo study |
| topic | lipid nanoparticles brain delivery nanostructured lipid carriers factorial design |
| url | https://www.mdpi.com/1999-4923/12/5/451 |
| work_keys_str_mv | AT nermineeleraky nanostructuredlipidcarrierstomediatebraindeliveryoftemazepamdesignandinvivostudy AT mahmoudmomar nanostructuredlipidcarrierstomediatebraindeliveryoftemazepamdesignandinvivostudy AT hematamahmoud nanostructuredlipidcarrierstomediatebraindeliveryoftemazepamdesignandinvivostudy AT hebaaaboutaleb nanostructuredlipidcarrierstomediatebraindeliveryoftemazepamdesignandinvivostudy |