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Controlled release of doxorubicin and Smac‐derived pro‐apoptotic peptide from self‐assembled KLD‐based peptide hydrogels
Author(s) -
YishaySafranchik Eliya,
Golan Moran,
David Ayelet
Publication year - 2014
Publication title -
polymers for advanced technologies
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.61
H-Index - 90
eISSN - 1099-1581
pISSN - 1042-7147
DOI - 10.1002/pat.3300
Subject(s) - self healing hydrogels , peptide , doxorubicin , drug delivery , in vitro , materials science , glycine , phenylalanine , biophysics , amino acid , biochemistry , chemistry , nanotechnology , polymer chemistry , biology , chemotherapy , genetics
Self‐assembled peptide hydrogels comprise an important class of biomaterials that find application in tissue engineering and drug delivery. We have developed injectable in situ ‐forming hydrogel formulations based on self‐assembled KLD motifs to control the delivery of a conventional cytotoxic drug (doxorubicin [DOX]) or a Smac‐derived pro‐apoptotic peptide (SDPP) for cancer therapy. The core KLD peptide ([KLDL] 3 ) was separated into two β‐sheet peptides by a three or four glycine‐containing spacer (designated as 3G or 4G, respectively) or by a spacer containing four glycines and a phenylalanine (termed 4GF) to fine tune and influence the bulk properties. We found that the KLD‐based hydrogel can effectively load DOX and SDPP within the hydrogel network. Addition of a three or four glycine‐containing spacer arm decreased the time for gel formation, while inclusion of a single aromatic amino acid (F) into 4G sequence (4GF) significantly increased the rate of gel formation and improved its mechanical strength when compared to 3G‐ and 4G‐containing gels. KLD16‐ and 4GF‐based hydrogels presenting higher peptide concentrations can self‐assemble very rapidly (in a few seconds) and were very effective at controlling the release of DOX and SDPP and inhibiting tumor cell growth in vitro . Pre‐complexation of SDPP with polyanionic molecule (polyglutamic acid) further sustained in vitro drug release from 4GF‐based formulations. This study is the first to test interactions between KLD‐based hydrogel matrices and DOX or SDPP for local drug delivery applications. Copyright © 2014 John Wiley & Sons, Ltd.