title: Controlled release of insulin from self-assembling nanofiber hydrogel, PuraMatrix™: application for the subcutaneous injection in rats.
abstract: The concept of this research is, using the acetyl-(Arg-Ala-Asp-Ala)₄-CONH₂ peptide hydrosol (PuraMatrix™, PM), to develop an new injectable formula of controlled insulin delivery for subcutaneous injection. PM has sol-gel phase transition behavior, and was developed as a scaffold in the field of tissue engineering. The aqueous media of the PM including insulin changed from a sol to a gel phase with increasing ion strength of phosphate ion and pH in working environments in vitro and in vivo. In this study, we examined the in vitro insulin dissolution behavior and the in vivo pharmacokinetics and pharmacodynamics after subcutaneous administration of PM-insulin sol (PM-Isol). In the in vitro release study, after PM-Isol was converted to a gel phase (PM-Igel), PM concentration-dependent and controlled release of insulin were observed at the final concentrations of PM between 0.1% and 2.0% (w/v). The PM-Isol is changed to gel form in vivo, and exhibited a sustained-release pharmacokinetics of insulin, where PM concentration-dependent prolongation of efficacy was found. The plasma glucose level markedly decreased, and the lowest plasma glucose level was maintained up to 24h when 2.0% (w/v) PM-Isol was administered subcutaneously to rats. The PM-Isol, we developed here, is applicable for the wild-type of insulin, and increased the bioavailability and hypoglycemic efficacy of insulin after subcutaneous injection. Hence, the PM is a useful inactive ingredient to produce various types of control-released system of insulin by making just a few changes in PM content of the formulation.
authors: Department of Biopharmaceutics, Doshisha Women's College of Liberal Arts, Kyotanabe, Kyoto 610-0395, Japan.
authors: Asako
authors: A
authors: Nishimura
authors: Taro
authors: T
authors: Hayakawa
authors: Yu
authors: Y
authors: Yamamoto
authors: Mami
authors: M
authors: Hamori
authors: Keiko
authors: K
authors: Tabata
authors: Keiko
authors: K
authors: Seto
authors: Nobuhito
authors: N
authors: Shibata
mesh_terms: D000818:Animals; D001682:Biological Availability; D001786:Blood Glucose / Q000032:analysis; D002417:Cattle; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004339:Drug Compounding; D020100:Hydrogels; D006863:Hydrogen-Ion Concentration; D007003:Hypoglycemia / Q000097:blood* / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D057139:Nanofibers / Q000737:chemistry*; D009994:Osmolar Concentration; D010455:Peptides / Q000737:chemistry*; D044367:Phase Transition; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
chemical_list: D001786:Blood Glucose; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; C546681:RADA16-I