title: A high-efficiency, low-toxicity, phospholipids-based phase separation gel for long-term delivery of peptides.
abstract: 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.
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors: Ting
authors: T
authors: Zhang
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors: Qiang
authors: Q
authors: Peng
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors: Feng-Ying
authors: FY
authors: San
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors: Jing-Wen
authors: JW
authors: Luo
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors: Meng-Xin
authors: MX
authors: Wang
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors: Wen-Qi
authors: WQ
authors: Wu
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address: gongtaoy@126.com.
authors: Tao
authors: T
authors: Gong
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address: zrzzl@vip.sina.com.
authors: Zhi-Rong
authors: ZR
authors: Zhang
mesh_terms: D000818:Animals; D004058:Diffusion; D016503:Drug Delivery Systems; D005782:Gels / Q000009:adverse effects* / Q000737:chemistry*; D007267:Injections; D008297:Male; D015282:Octreotide / Q000008:administration & dosage; D010455:Peptides / Q000008:administration & dosage*; D044367:Phase Transition; D010743:Phospholipids / Q000009:adverse effects / Q000737:chemistry*; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D012996:Solutions; D012997:Solvents / Q000737:chemistry; D013194:Staining and Labeling; D013997:Time Factors; D014783:Viscosity; D014867:Water / Q000737:chemistry
chemical_list: D005782:Gels; D010455:Peptides; D010743:Phospholipids; D012996:Solutions; D012997:Solvents; D014867:Water; D015282:Octreotide
keywords: Drug delivery; Gel; Implant; Irritation; Long-term release; Phospholipid