Key functions in polymer carriers for intestinal absorption of insulin.
This work aimed to clarify the relationship between polymer function and insulin absorption, and to evaluate the optimized preparative formulation predicted from this relationship. Insulin-loaded polymer (ILP) carrier systems were prepared following a two-factor composite second-order spherical experimental design. To investigate the polymer function, we evaluated its insulin release, bioadhesiveness, and protective effect. Each ILP was administered intestinally, and glucose reduction was monitored as the pharmacological effect. Based on these data, an optimized formulation was predicted and how the polymer function affects insulin absorption was clarified by multivariate spline (MVS) interpolation. A greater pharmacological effect was apparent in ILPs with a smaller particle size and loaded with more insulin. The pharmacological effect predicted by MVS after the administration of ILP made under optimized preparative conditions was almost identical to the observed effect. Moreover, MVS clarified the relationship between the polymer function and the pharmacological effect. These results supported that MVS can be an effective tool with which to approximate the relationship between the function of a dosage form and its absorption, and to explore the optimized preparative conditions.
Nakamura
Koji
K
Department of Pharmaceutics, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
Morishita
Mariko
M
Ehara
Junpei
J
Onuki
Yoshinori
Y
Yamagata
Tetsuo
T
Kamei
Noriyasu
N
Lowman
Anthony M
AM
Peppas
Nicholaos A
NA
Takayma
Kozo
K
D000268:Adhesiveness; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D008863:Microspheres; D015999:Multivariate Analysis; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D011108:Polymers; D011109:Polymethacrylic Acids; D011092:Polyethylene Glycols