Characterization of a smart pH-cleavable PEG polymer towards the development of dual pH-sensitive liposomes.

Show simple item record Kanamala, Manju en Palmer, Brian en Wilson, William en Wu, Zimei en 2019-03-13T22:03:17Z en 2018-09 en
dc.identifier.issn 0378-5173 en
dc.identifier.uri en
dc.description.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 24 h. In comparison, at pH 5.5 and pH 6.5 PEG detachment within 1 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 (123 nm) were shown to be sable at least for 3 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. en
dc.format.medium Print-Electronic en
dc.language eng en
dc.relation.ispartofseries International journal of pharmaceutics en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.subject Polyethylene Glycols en
dc.subject Benzaldehydes en
dc.subject Fluoresceins en
dc.subject Cholesterol Esters en
dc.subject Lipids en
dc.subject Liposomes en
dc.subject Hydrogen-Ion Concentration en
dc.title Characterization of a smart pH-cleavable PEG polymer towards the development of dual pH-sensitive liposomes. en
dc.type Journal Article en
dc.identifier.doi 10.1016/j.ijpharm.2018.07.009 en
pubs.issue 1 en
pubs.begin-page 288 en
pubs.volume 548 en
dc.rights.holder Copyright: The author en
pubs.end-page 296 en
pubs.publication-status Published en
dc.rights.accessrights en
pubs.subtype Journal Article en
pubs.elements-id 747812 en Medical and Health Sciences en Medical Sciences en Auckland Cancer Research en Pharmacy en Science en Science Research en Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 1873-3476 en
pubs.record-created-at-source-date 2018-07-08 en
pubs.dimensions-id 29981407 en

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