title: A rapid-acting, long-acting insulin formulation based on a phospholipid complex loaded PHBHHx nanoparticles.
abstract: The application of poly(hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) for sustained and controlled delivery of hydrophilic insulin was made possible by preparing insulin phospholipid complex loaded biodegradable PHBHHx nanoparticles (INS-PLC-NPs). The INS-PLC-NPs produced by a solvent evaporation method showed a spherical shape with a mean particle size, zeta potential and entrapment efficiency of 186.2 nm, -38.4 mv and 89.73%, respectively. In vitro studies demonstrated that only 20% of insulin was released within 31 days with a burst release of 5.42% in the first 8 h. The hypoglycaemic effect in STZ induced diabetic rats lasted for more than 3 days after the subcutaneous injection of INS-PLC-NPs, which significantly prolonged the therapeutic effect compared with the administration of insulin solution. The pharmacological bioavailability (PA) of INS-PLC-NPs relative to insulin solution was over 350%, indicating that the bioavailability of insulin was significantly enhanced by INS-PLC-NPs. Therefore, the INS-PLC-NPs system is promising to serve as a long lasting insulin release formulation, by which the patient compliance can be enhanced significantly. This study also showed that phospholipid complex loaded biodegradable nanoparticles (PLC-NPs) have a great potential to be used as a sustained delivery system for hydrophilic proteins to be encapsulated in hydrophobic polymers.
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, PR China.
authors: Qiang
authors: Q
authors: Peng
authors: Zhi-Rong
authors: ZR
authors: Zhang
authors: Tao
authors: T
authors: Gong
authors: Guo-Qiang
authors: GQ
authors: Chen
authors: Xun
authors: X
authors: Sun
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000737:chemistry*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002208:Caproates / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D005612:Freeze Drying; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007279:Injections, Subcutaneous; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010743:Phospholipids / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility / Q000187:drug effects; D013997:Time Factors; D014867:Water / Q000737:chemistry; D000094122:Polyhydroxybutyrates
chemical_list: D020155:3-Hydroxybutyric Acid; D001786:Blood Glucose; D002208:Caproates; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D010743:Phospholipids; D014867:Water; C115940:poly(3-hydroxybutyrate-co-3-hydroxyhexanoate); D000094122:Polyhydroxybutyrates