title: Beneficial properties for insulin absorption using superporous hydrogel containing interpenetrating polymer network as oral delivery vehicles.
abstract: In this investigation, superporous hydrogels containing poly (acrylic acid-co-acrylamide)/O-carboxymethyl chitosan (O-CMC) full-interpenetrating polymer networks (SPH-IPNs) were evaluated for their potentials in effective insulin absorption via the oral route. Insulin release from the SPH-IPNs exhibited sensitivity towards pH and ionic strength. After drug loading and release, the circular dichroism (CD) spectra revealed that conformation of insulin had no significant alteration and bioactivity of insulin was well preserved according to hypoglycaemic effect in mice. Through their abilities to bind Ca(2+) and to entrap the enzymes, SPH-IPNs could partly inactivate trypsin and alpha-chymotrypsin, and SPH-IPN with higher O-CMC/monomer ratio appeared more potent. Swollen SPH-IPNs could attach mechanically and muco-adhere to the intestinal wall, thus achieving improved retentive properties compared to commonly used muco-adhesive excipient Carbopol 934. Transport of insulin across rat intestine and colon ex vivo was enhanced around two- to three-fold after application of the SPH-IPN. Insulin-loaded SPH-IPN showed significant hypoglycaemic effects following oral administration to healthy rats, achieving a 4.1% pharmacological availability compared to subcutaneous insulin injection. These pronounced properties demonstrated that the SPH-IPN would be a promising peroral carrier for insulin and other peptide drugs.
authors.affiliation: School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Lichen
authors.initials: L
authors.lastname: Yin
authors.forename: Jieying
authors.initials: J
authors.lastname: Ding
authors.forename: Likun
authors.initials: L
authors.lastname: Fei
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.forename: Fuying
authors.initials: F
authors.lastname: Cui
authors.forename: Cui
authors.initials: C
authors.lastname: Tang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Yin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002118:Calcium / Q000737:chemistry; D048271:Chitosan / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D003300:Copper / Q000737:chemistry; D004355:Drug Stability; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage*; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D008297:Male; D009994:Osmolar Concentration; D014677:Pharmaceutical Vehicles; D016062:Porosity; D011487:Protein Conformation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014361:Trypsin Inhibitors / Q000494:pharmacology
chemical_list: D007328:Insulin; C504164:O-carboxymethylchitosan; D014677:Pharmaceutical Vehicles; D014361:Trypsin Inhibitors; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D003300:Copper; D048271:Chitosan; D002918:Chymotrypsin; C117608:alpha-chymotrypsin; D002118:Calcium