Journal
BIOMATERIALS
Volume 45, Issue -, Pages 1-9Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.12.042
Keywords
Gel; Implant; Drug delivery; Phospholipid; Long-term release; Irritation
Funding
- National S & T Major Project of China [2012ZX09304004]
- National Basic Research Program of China (973 program) [2013CB932504]
- National Natural Science Foundation of China [81273443]
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Peptide and protein drugs are currently under rapid development attributed to their high potency and efficacy in therapy. Their successful delivery, however, is highly limited by their short half-life, fast degradation and rapid clearance. Here, we present a high content phospholipids-based phase separation gel (PPSG), which is readily injectable due to its low initial viscosity and can rapidly transform into an in situ implant after injection upon exposure to an aqueous environment. A selected model peptide, octreotide acetate, is loaded into PPSG and achieves sustained release profiles for one month in rats. In addition, the local irritation caused by ethanol contained in PPSG is ethanol content-dependent and the irritation of PPSG with 70% phospholipids content can be eliminated by partially replacing ethanol with medium chain triglyceride. The mechanisms underlying phase transition of PPSG are based on water-insolubility of phospholipids. Our findings demonstrate that PPSG is a readily injectable, highly safe and efficient in situ forming implant for sustained delivery of peptides. (C) 2014 Elsevier Ltd. All rights reserved.
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