title: Enhanced oral bioavailability of insulin using PLGA nanoparticles co-modified with cell-penetrating peptides and Engrailed secretion peptide (Sec).
abstract: Biodegradable polymer nanoparticle drug carriers are an attractive strategy for oral delivery of peptide and protein drugs. However, their ability to cross the intestinal epithelium membrane is largely limited. Therefore, in the present study, cell-penetrating peptides (R8, Tat, penetratin) and a secretion peptide (Sec) with N-terminal stearylation were introduced to modify nanoparticles (NPs) on the surface to improve oral bioavailability of peptide and protein drugs. In vitro studies conducted in Caco-2 cells showed the value of the apparent permeability coefficient (Papp) of the nanoparticles co-modified with Sec and penetratin (Sec-Pen-NPs) was about two-times greater than that of the nanoparticles modified with only penetratin (Pen-NPs), while the increase of transcellular transport of nanoparticles modified together with Sec and R8 (Sec-R8-NPs), or Sec and Tat (Sec-Tat-NPs), was not significant compared with nanoparticles modified with only R8 (R8-NPs) or Tat (Tat-NPs). Using insulin as the model drug, in vivo studies performed on rats indicated that compared to Pen-NPs, the relative bioavailability of insulin for Sec-Pen-NPs was 1.71-times increased after ileal segments administration, and stronger hypoglycemic effects was also observed. Therefore, the nanoparticles co-modified with penetratin and Sec could act as attractive carriers for oral delivery of insulin.
authors.affiliation: a School of Pharmacy, Nanchang University , Jiangxi , China and.
authors.forename: Siqi
authors.initials: S
authors.lastname: Zhu
authors.affiliation: a School of Pharmacy, Nanchang University , Jiangxi , China and.
authors.forename: Shuangxi
authors.initials: S
authors.lastname: Chen
authors.affiliation: a School of Pharmacy, Nanchang University , Jiangxi , China and.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: a School of Pharmacy, Nanchang University , Jiangxi , China and.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: a School of Pharmacy, Nanchang University , Jiangxi , China and.
authors.forename: Fengying
authors.initials: F
authors.lastname: Li
authors.affiliation: a School of Pharmacy, Nanchang University , Jiangxi , China and.
authors.forename: Baogang
authors.initials: B
authors.lastname: Xie
authors.affiliation: b Department of Cardiothoracic Surgery , The Second Affiliated Hospital of Nanchang University , Jiangxi , China.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Zhou
authors.affiliation: a School of Pharmacy, Nanchang University , Jiangxi , China and.
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhong
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010539:Permeability; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D007328:Insulin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Cell-penetrating peptides; Engrailed secretion peptide (Sec); nanoparticles; oral administration; peptide and protein drugs