title: Poly(ester amide) blend microspheres for oral insulin delivery.
abstract: This study developed a novel oral insulin formulation centered on microspheres consisting of a blend of biodegradable poly(ester amide) (PEA). In the formulation, L-lysine-/L-leucine-based PEA with pendant COOH groups (PEA-COOH) was used as a pH-responsive material for the protection of insulin from the harsh environmental conditions of the stomach. Arginine-based PEA (Arg-PEA) was introduced to improve the intestinal absorption of the drug. The influence of both the hydrophobicity of PEA-COOH and the content of Arg-PEA was investigated in detail on microsphere surface morphology, drug loading, and the in vitro release profile of insulin. The PEA-COOH/Arg-PEA blend microspheres protected the loaded insulin in simulated gastric fluid and released insulin in a fast and sustained manner in simulated intestinal fluid. The in vivo test demonstrated that the oral administration of insulin-loaded PEA blend microspheres could effectively suppress the blood glucose level in diabetic rats for 10h, and the oral bioavailability was improved to 5.89+1.84% in healthy rats. These results indicate that the PEA blend microspheres are promising vehicles for the oral delivery of insulin.
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
authors.forename: Pan
authors.initials: P
authors.lastname: He
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Liu
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.forename: Mingxiao
authors.initials: M
authors.lastname: Deng
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Xuan
authors.initials: X
authors.lastname: Pang
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001120:Arginine / Q000737:chemistry; D001682:Biological Availability; D003921:Diabetes Mellitus, Experimental; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D007930:Leucine / Q000737:chemistry; D008239:Lysine / Q000737:chemistry; D008297:Male; D008863:Microspheres; D009757:Nylons / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D009757:Nylons; D011091:Polyesters; D001120:Arginine; D007930:Leucine; D008239:Lysine
keywords: Arg-PEA; Blend microspheres; CLSM; DMA; DMF; DMSO; EE; ESEM; FITC; GI; L0.2; L0.2–30A; N,N-dimethylformamide; Oral insulin delivery; P(MAA-g-EG); PEA; PEA-COOH; PEA-COOH with 20% (molar content) of leucine-based monomer; Poly(ester amide); S/O/O; SC; SDS; SEM; STZ; Span83; arginine-based poly(ester amide); blend microspheres containing 30% Arg-PEA and 70% L0.2 by weight; dimethyl acetamide; dimethyl sulfoxide; encapsulation efficiency; environmental scanning electron microscopy; fluorescein isothiocyanate; gastrointestinal; laser scanning confocal microscopy; pH sensitivity; poly(ester amide); poly(ester amide) with pendant COOH groups; poly(methacrylic-g-ethylene glycol); scanning electron microscopy; sodium dodecyl sulphate; solid-in-oil-in-oil; sorbitan sesquioleate; streptozotocin; subcutaneous