title: The implantable and biodegradable PHBHHx 3D scaffolds loaded with protein-phospholipid complex for sustained delivery of proteins.
abstract: OBJECTIVE
  PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) is an excellent biomaterial for tissue repair. Here, we aim to develop a PHBHHx-based three-dimensional (3D) scaffold system for sustained delivery of proteins (insulin serves as a model protein).
  
  
  METHODS
  The insulin-phospholipid complex (INS-PLC) was prepared to enhance the insulin lipophilicity. INS-PLC loaded PHBHHx 3D scaffolds (INS-PLC-SCAs) containing PEG-2000 were fabricated by lyophilization. In vitro release was performed in the medium with or without lipase. The bioactivity of INS-PLC-SCAs was measured in diabetic rats.
  
  
  RESULTS
  In vitro release shows that the release rate of INS-PLC-SCAs was very slow (~6% of total insulin was released within 120 days), and PEG-2000 or lipase had no effect on its release pattern. The bioactivity test shows that the hypoglycaemic effect of insulin was maintained after formulated into scaffolds. After subcutaneous (s.c.) implantation, its therapeutic effect lasted for over 130 h, and its bioavailability was enhanced by 4-fold.
  
  
  CONCLUSIONS
  PHBHHx based 3D scaffold has a great potential for sustained delivery of proteins, especially growth factors. When growth factors are incorporated, it can serve as a bifunctional system that provides a porous skeleton for cells attachment and proliferation, as well as a matrix for long term release of the loaded growth factors.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Section 3, South Renmin Road, Chengdu, 610041, People's Republic of China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Peng
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Yang
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Wu
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Zhang
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002208:Caproates / Q000737:chemistry* / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D010743:Phospholipids / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054457:Tissue Scaffolds / Q000737:chemistry; D000094122:Polyhydroxybutyrates
chemical_list: D020155:3-Hydroxybutyric Acid; D001672:Biocompatible Materials; D002208:Caproates; D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D007328:Insulin; D010743:Phospholipids; C115940:poly(3-hydroxybutyrate-co-3-hydroxyhexanoate); D000094122:Polyhydroxybutyrates