Use of a non-covalent cell-penetrating peptide strategy to enhance the nasal delivery of interferon beta and its PEGylated form.
Int J Pharm
; 510(1): 304-10, 2016 Aug 20.
Article
em En
| MEDLINE
| ID: mdl-27343364
ABSTRACT
The conjugation of therapeutic proteins to polyethylene glycol (PEG) is known as PEGylation. It improves their retention in the body and reduces the frequency of injections. Development of noninvasive delivery systems for biopharmaceuticals can improve the patients' quality of life. The present study aimed to evaluate the cell-penetrating peptides (CPPs), which act as bioenhancers, for the nasal delivery of protein drug interferon beta (IFN-ß) and its PEGylated form (PEG-IFN-ß). The ability of CPPs to enhance the nasal mucosal absorption of unmodified IFN-ß was assessed in rats. It was shown that only d-amino acid forms of amphipathic CPPs, penetratin and PenetraMax significantly enhanced the nasal absorption of IFN-ß. Especially, D-penetratin (up to 2mM) enhanced the absorption of INF-ß in a dose-dependent manner. The maximum absolute bioavailability reached 8.26% following in situ nasal coadministration of IFN-ß with d-penetratin (2mM). Furthermore, it was found that the coadministration of d-penetratin also facilitated the nasal absorption of PEG-IFN-ß, which remained in the circulation for more than 6h. Moreover, the toxicity assessments showed no damage to the epithelial membranes after nasal administration of CPPs including penetratin and PenetraMax. Altogether, this study provides the first evidence that the noncovalent coadministration of PEGylated proteins with CPPs could be a potent strategy for the noninvasive and sustained nasal delivery of therapeutic proteins.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polietilenoglicóis
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Interferon beta
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Sistemas de Liberação de Medicamentos
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Peptídeos Penetradores de Células
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Mucosa Nasal
Aspecto:
Patient_preference
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Japão