Exendin-4 Loaded Nanoparticles with a Lipid Shell and Aqueous Core Containing Micelles for Enhanced Intestinal Absorption.
The purpose of this study was to formulate nanoparticles with an elaborate structure for oral delivery of exendin-4 using a simple preparation process. The nanoparticles possessed a mixed lipid shell and an aqueous core which contained drug-loaded micelles. Formulation was optimized by a central composite design and the structure of the nanoparticles was validated. The efficacy for delivery of exendin-4 was evaluated both in vitro and in vivo. The drug encapsulation efficiency of the nanoparticles reached 97.7%. The nanoparticles greatly enhanced the cellular uptake and transport of encapsulated exendin-4 in vitro. The in situ study showed that exendin-4 could be transported across the epithelium into intestinal capillaries, while the lipid materials largely remained in the epithelium. Pharmacodynamic studies in diabetic KKAy mice demonstrated that the exendin-4-loaded nanoparticles exhibited a marked hypoglycemia effect with a pharmacological availability of 12.7% after intestinal administration.
Chunhui
C
Chen
Xi
X
Zhu
Yanfeng
Y
Dou
Juan
J
Xu
Jian
J
Zhang
Tingting
T
Fan
Junrong
J
Du
Ke
K
Liu
Yihong
Y
Deng
Liyan
L
Zhao
Yuan
Y
Huang
D000818:Animals; D018938:Caco-2 Cells; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry; D000077270:Exenatide; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000187:drug effects; D008081:Liposomes / Q000737:chemistry; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008822:Mice, Transgenic; D008823:Micelles; D053758:Nanoparticles / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014688:Venoms / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014867:Water / Q000737:chemistry
D004337:Drug Carriers; D007004:Hypoglycemic Agents; D008081:Liposomes; D008823:Micelles; D010455:Peptides; D014688:Venoms; D014867:Water; D000077270:Exenatide