Development of chitosan nanoparticles as drug delivery system for a prototype capsid inhibitor.
Int J Pharm
; 495(2): 771-82, 2015 Nov 30.
Article
em En
| MEDLINE
| ID: mdl-26428629
ABSTRACT
Oral delivery of biopharmaceutics drug disposition classification system (BDDCS) Class II or IV drugs with poor aqueous solubility and poor enzymatic and/or metabolic stability is very challenging. Bay41-4109, a member of the heteroaryldihydropyrimidine (HAP) family, inhibits HBV replication by destabilizing capsid assembly. It pertains to class II of the BDDCS which has a practically insoluble solubility which is 38 µg/mL (LYSA) and the oral delivery resulted in low bioavailability. The purpose of the current research work was to develop and evaluate Bay41-4109 loaded chitosan nanoparticles to increase the solubility and bioavailability for treatment of HBV. The Bay41-4109 nanoparticles were prepared by gelation of chitosan with tripolyphosphate (TPP) through ionic cross-linking. A three-factor three-level central composite design (CCD) was introduced to perform the experiments. A quadratic polynomial model was generated to predict and evaluate the independent variables with respect to the dependent variables. Bay41-4109 was encapsulated in the chitosan nanoparticles were demonstrated by PLM, FTIR, DSC, XRD and TEM etc. The in vivo results suggest that Bay41-4109 nanoparticles have better bioavailability and would be a promising approach for oral delivery of Bay41-4109 for the treatment of HBV.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
Base de dados:
MEDLINE
Assunto principal:
Piridinas
/
Pirimidinas
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Sistemas de Liberação de Medicamentos
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Quitosana
/
Nanopartículas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2015
Tipo de documento:
Article