title: Injectable and biodegradable thermosensitive hydrogels loaded with PHBHHx nanoparticles for the sustained and controlled release of insulin.
abstract: Biodegradable PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) nanoparticles containing insulin phospholipid complex were loaded in chitosan-based thermosensitive hydrogels for long-term sustained and controlled delivery of insulin. The injectable hydrogels, prepared by adding β-glycerophosphate disodium salt (GP) solution to chitosan (CS) solution under stirring, showed a rapid solution-to-gel transition at 37 °C, a porous structure and a comparative degradation and swelling rate in vitro. In the in vitro release studies, only 19.11% of total insulin was released from the nanoparticle-loaded hydrogel (NP-CS/GP) within 31 days. However, 96.41% of total insulin was released from the free insulin-loaded hydrogel (INS-CS/GP) within 16 days. Most importantly, the hypoglycemic effect of NP-CS/GP following subcutaneous injection in diabetic rats lasted for >5 days, much longer than the effect caused by INS-CS/GP or other long-acting insulin formulations. The pharmacological availability of NP-CS/GP relative to INS-CS/GP was 379.85%, indicating that the bioavailability of insulin was significantly enhanced by NP-CS/GP gels. Therefore, biodegradable and thermosensitive NP-CS/GP gels have great potential for use in novel ultralong-acting insulin injections. In addition, the NP-loaded hydrogel system also paves the way for long-term delivery of other proteins and peptides.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, People's Republic of China.
authors.forename: Q
authors.initials: Q
authors.lastname: Peng
authors.forename: X
authors.initials: X
authors.lastname: Sun
authors.forename: T
authors.initials: T
authors.lastname: Gong
authors.forename: C-Y
authors.initials: CY
authors.lastname: Wu
authors.forename: T
authors.initials: T
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Tan
authors.forename: Z-R
authors.initials: ZR
authors.lastname: Zhang
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000737:chemistry*; D000818:Animals; D001673:Biodegradation, Environmental; D001786:Blood Glucose / Q000187:drug effects; D002208:Caproates / Q000737:chemistry*; D048271:Chitosan / Q000737:chemistry; D003692:Delayed-Action Preparations; D005994:Glycerophosphates / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007267:Injections; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions; D034421:Sus scrofa; D013696:Temperature; D000094122:Polyhydroxybutyrates
chemical_list: D020155:3-Hydroxybutyric Acid; D001786:Blood Glucose; D002208:Caproates; D048271:Chitosan; D003692:Delayed-Action Preparations; D005994:Glycerophosphates; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007004:Hypoglycemic Agents; D007328:Insulin; D012996:Solutions; C115940:poly(3-hydroxybutyrate-co-3-hydroxyhexanoate); D000094122:Polyhydroxybutyrates; C031463:beta-glycerophosphoric acid