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

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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Bibliographic Details
Published in:Polymers Vol. 15; no. 19; p. 3890
Main Authors: Badran, Mohamed M, Alanazi, Abdulrahman E, Ibrahim, Mohamed Abbas, Alshora, Doaa Hasan, Taha, Ehab, H. Alomrani, Abdullah
Format: Journal Article
Language:English
Published: Basel MDPI AG 26-09-2023
MDPI
Subjects:
Bioavailability
Biocompatibility
Brain
Bromocriptine
bromocriptine mesylate
Chitosan
chitosan coating
Dependent variables
Design of experiments
Design parameters
Dopamine
Drug delivery systems
Drugs
Efficiency
Entrapment
ex vivo permeation
Factorial design
Hemodialysis
In vivo methods and tests
Molecular weight
Nanoparticles
Nose
Optimization
Particle size
Permeability
poly ε-caprolactone nanoparticles
Polycaprolactone
Polyethylene glycol
Polyols
Response surface methodology
Solvents
Sustained release
Tocopherol
Type 2 diabetes
Zeta potential
Germany
United Kingdom > UK
United States > US
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Summary: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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ISSN:2073-4360
2073-4360
DOI:10.3390/polym15193890