Characterization of a smart pH-cleavable PEG polymer towards the development of dual pH-sensitive liposomes.
Int J Pharm
; 548(1): 288-296, 2018 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-29981407
ABSTRACT
To facilitate the development of PEG-cleavable pH-sensitive liposomes (CL-pPSL), this study aimed to fully characterize a new pH-sensitive polymer, PEGB-Hz-CHEMS. Polyethylene glycol (PEG) functionalised with 4-carboxybenzaldehyde (PEGB) was linked to cholesteryl hemisuccinate (CHEMS) via an acid labile hydrazide-hydrazone hybrid bond (CONHNCH) to form PEGB-Hz-CHEMS. The polymer was post-inserted into DOPE/CHEMS liposomes to form CL-pPSL. A validated stability-indicating HPLC-UV method was developed with the aid of multiple linear regression for the mobile phase. The assay was used to evaluate the pH-sensitivity, pathways of cleavage of the polymer and the PEGylation degree of CL-pPSL. The pH-sensitivity of CL-pPSL was compared with conventional PEGylated pH-sensitive (pPSL) using a calcein leakage assay. At 37⯰C, PEGB-Hz-CHEMS was relatively stable at pH 7.4 with a half-life of 24â¯h. In comparison, at pH 5.5 and pH 6.5 PEG detachment within 1â¯h was determined as 80%, and 50%, respectively. PEG detachment of the polymer was through simultaneous cleavage of the hydrazine (CON) and hydrazone (NC) bonds, depending on pH, thus the polymer is more pH-sensitive than those with a hydrazine bond only. The grafting densities of PEGB-Hz-CHEMS on CL-pPSL were optimised to achieve a PEG density of 1.7% (mol). The unilamellar CL-pPSL (123â¯nm) were shown to be sable at least for 3â¯months at 4⯰C and have enhanced pH-sensitivity compared with pPSL in the calcein leakage assay. Therefore, the smart cleavable PEG polymer is promising in liposome formulation to overcome the PEG dilemma.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polietilenoglicóis
/
Lipossomos
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Revista:
Int J Pharm
Ano de publicação:
2018
Tipo de documento:
Article