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Optimization of Bromocriptine-Mesylate-Loaded Polycaprolactone Nanoparticles Coated with Chitosan for Nose-to-Brain Delivery: In Vitro and In Vivo Studies

Bromocriptine mesylate (BM), primarily ergocryptine, is a dopamine agonist derived from ergot alkaloids. This study aimed to formulate chitosan (CS)-coated poly ε-caprolactone nanoparticles (PCL NPs) loaded with BM for direct targeting to the brain via the nasal route. PCL NPs were optimized using r...

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Detalles Bibliográficos
Autores principales: Badran, Mohamed M., Alanazi, Abdulrahman E., Ibrahim, Mohamed Abbas, Alshora, Doaa Hasan, Taha, Ehab, H. Alomrani, Abdullah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10574927/
https://www.ncbi.nlm.nih.gov/pubmed/37835942
http://dx.doi.org/10.3390/polym15193890
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author Badran, Mohamed M.
Alanazi, Abdulrahman E.
Ibrahim, Mohamed Abbas
Alshora, Doaa Hasan
Taha, Ehab
H. Alomrani, Abdullah
author_facet Badran, Mohamed M.
Alanazi, Abdulrahman E.
Ibrahim, Mohamed Abbas
Alshora, Doaa Hasan
Taha, Ehab
H. Alomrani, Abdullah
author_sort Badran, Mohamed M.
collection PubMed
description Bromocriptine mesylate (BM), primarily ergocryptine, is a dopamine agonist derived from ergot alkaloids. This study aimed to formulate chitosan (CS)-coated poly ε-caprolactone nanoparticles (PCL NPs) loaded with BM for direct targeting to the brain via the nasal route. PCL NPs were optimized using response surface methodology and a Box–Behnken factorial design. Independent formulation parameters for nanoparticle attributes, including PCL payload (A), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) concentration (B), and sonication time (C), were investigated. The dependent variables were nanoparticle size (Y1), zeta potential (Y2), entrapment efficiency (EE; Y3), and drug release rate (Y4). The optimal formulation for BM-PCL NPs was determined to be 50 mg PCL load, 0.0865% TPGS concentration, and 8 min sonication time, resulting in nanoparticles with a size of 296 ± 2.9 nm having a zeta potential of −16.2 ± 3.8 mV, an EE of 90.7 ± 1.9%, and a zero-order release rate of 2.6 ± 1.3%/min. The optimized BM-PCL NPs were then coated with CS at varying concentrations (0.25, 0.5, and 1%) to enhance their effect. The CS-PCL NPs exhibited different particle sizes and zeta potentials depending on the CS concentration used. The highest EE (88%) and drug load (DL; 5.5%) were observed for the optimized BM-CS-PCL NPs coated with 0.25% CS. The BM-CS-PCL NPs displayed a biphasic release pattern, with an initial rapid drug release lasting for 2 h, followed by a sustained release for up to 48 h. The 0.25% CS-coated BM-CS-PCL NPs showed a high level of permeation across the goat nasal mucosa, with reasonable mucoadhesive strength. These findings suggested that the optimized 0.25% CS-coated BM-CS-PCL NPs hold promise for successful nasal delivery, thereby improving the therapeutic efficacy of BM.
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spelling pubmed-105749272023-10-14 Optimization of Bromocriptine-Mesylate-Loaded Polycaprolactone Nanoparticles Coated with Chitosan for Nose-to-Brain Delivery: In Vitro and In Vivo Studies Badran, Mohamed M. Alanazi, Abdulrahman E. Ibrahim, Mohamed Abbas Alshora, Doaa Hasan Taha, Ehab H. Alomrani, Abdullah Polymers (Basel) Article Bromocriptine mesylate (BM), primarily ergocryptine, is a dopamine agonist derived from ergot alkaloids. This study aimed to formulate chitosan (CS)-coated poly ε-caprolactone nanoparticles (PCL NPs) loaded with BM for direct targeting to the brain via the nasal route. PCL NPs were optimized using response surface methodology and a Box–Behnken factorial design. Independent formulation parameters for nanoparticle attributes, including PCL payload (A), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) concentration (B), and sonication time (C), were investigated. The dependent variables were nanoparticle size (Y1), zeta potential (Y2), entrapment efficiency (EE; Y3), and drug release rate (Y4). The optimal formulation for BM-PCL NPs was determined to be 50 mg PCL load, 0.0865% TPGS concentration, and 8 min sonication time, resulting in nanoparticles with a size of 296 ± 2.9 nm having a zeta potential of −16.2 ± 3.8 mV, an EE of 90.7 ± 1.9%, and a zero-order release rate of 2.6 ± 1.3%/min. The optimized BM-PCL NPs were then coated with CS at varying concentrations (0.25, 0.5, and 1%) to enhance their effect. The CS-PCL NPs exhibited different particle sizes and zeta potentials depending on the CS concentration used. The highest EE (88%) and drug load (DL; 5.5%) were observed for the optimized BM-CS-PCL NPs coated with 0.25% CS. The BM-CS-PCL NPs displayed a biphasic release pattern, with an initial rapid drug release lasting for 2 h, followed by a sustained release for up to 48 h. The 0.25% CS-coated BM-CS-PCL NPs showed a high level of permeation across the goat nasal mucosa, with reasonable mucoadhesive strength. These findings suggested that the optimized 0.25% CS-coated BM-CS-PCL NPs hold promise for successful nasal delivery, thereby improving the therapeutic efficacy of BM. MDPI 2023-09-26 /pmc/articles/PMC10574927/ /pubmed/37835942 http://dx.doi.org/10.3390/polym15193890 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Badran, Mohamed M.
Alanazi, Abdulrahman E.
Ibrahim, Mohamed Abbas
Alshora, Doaa Hasan
Taha, Ehab
H. Alomrani, Abdullah
Optimization of Bromocriptine-Mesylate-Loaded Polycaprolactone Nanoparticles Coated with Chitosan for Nose-to-Brain Delivery: In Vitro and In Vivo Studies
title Optimization of Bromocriptine-Mesylate-Loaded Polycaprolactone Nanoparticles Coated with Chitosan for Nose-to-Brain Delivery: In Vitro and In Vivo Studies
title_full Optimization of Bromocriptine-Mesylate-Loaded Polycaprolactone Nanoparticles Coated with Chitosan for Nose-to-Brain Delivery: In Vitro and In Vivo Studies
title_fullStr Optimization of Bromocriptine-Mesylate-Loaded Polycaprolactone Nanoparticles Coated with Chitosan for Nose-to-Brain Delivery: In Vitro and In Vivo Studies
title_full_unstemmed Optimization of Bromocriptine-Mesylate-Loaded Polycaprolactone Nanoparticles Coated with Chitosan for Nose-to-Brain Delivery: In Vitro and In Vivo Studies
title_short Optimization of Bromocriptine-Mesylate-Loaded Polycaprolactone Nanoparticles Coated with Chitosan for Nose-to-Brain Delivery: In Vitro and In Vivo Studies
title_sort optimization of bromocriptine-mesylate-loaded polycaprolactone nanoparticles coated with chitosan for nose-to-brain delivery: in vitro and in vivo studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10574927/
https://www.ncbi.nlm.nih.gov/pubmed/37835942
http://dx.doi.org/10.3390/polym15193890
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