Effective encapsulation of apomorphine into biodegradable polymeric nanoparticles through a reversible chemical bond for delivery across the blood-brain barrier.
Nanomedicine
; 17: 236-245, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-30738234
ABSTRACT
Apomorphine (AMP, used for treatment of Parkinson's disease) is susceptible to oxidation. Its oxidized products are toxic. To overcome these issues, AMP was conjugated to phenylboronic acid-functionalized polycarbonate through pH-sensitive covalent boronate ester bond between phenylboronic acid and catechol in AMP. Various conditions (use of base as catalyst, reaction time and initial drug loading) were optimized to achieve high AMP conjugation degree and mitigate polymer degradation caused by amine in AMP. Pyridine accelerated AMP conjugation and yielded ~74% conjugation within 5 min. Tertiary amine groups were incorporated to polycarbonate, and served as efficient catalyst (~80% conjugation within 5 min). AMP-conjugated polymer self-assembled into nanoparticles. AMP release from the nanoparticles was minimal at pH 7.4, while in acidic environment (endolysosomes) rapid release was observed. Encapsulation protected AMP from oxidization. The nanoparticles were significantly accumulated in the brain tissue after intranasal delivery. These AMP-loaded nanoparticles have potential use for treatment of Parkinson's disease.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cimento de Policarboxilato
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Portadores de Fármacos
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Apomorfina
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Agonistas de Dopamina
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article