title: Modified nanoparticles with cell-penetrating peptide and amphipathic chitosan derivative for enhanced oral colon absorption of insulin: preparation and evaluation.
abstract: Colon is an ideal absorptive site for oral protein and peptide drug (insulin), and yet it poses multiple barriers against the drug absorption, such as the barriers against the drug diffusion from colon lumen toward the absorptive mucosa and permeation across colon epithelium. In this study, modified nanoparticles (Tat-CS-NPs) with cell-penetrating peptide (Tat) and amphipathic chitosan derivative (a-CS) were used as carriers to improve colonic absorption of the drug. With a-CS as emulsifier and poly(lactic-co-glycolic acid) as matrix material, Tat-CS-NPs were prepared and evaluated in vitro/vivo. Using Caco-2 cell monolayers to imitate the colonic epithelial cells, it was found that the cellular uptake amount and transcellular transportation performance of Tat-CS-NPs were much enhanced compared with those of CS-NPs and PVA-NPs. The efficacy evaluation on diabetic rat models demonstrated that the hypoglycemic effect of Tat-CS-NPs loaded with insulin was 6.89 times higher than that of PVA-NPs, and 1.79 times higher than that of CS-NPs. By gavage of [(99m)Tc] isotope labeled Tat-CS-NPs in mini-pigs and single-photon emission computed tomography (SPECT) on pigs' gastrointestinal tract, it was further proved that the nanoparticles could reach colon and produce pharmacological effect. In conclusion, Tat-CS-NPs as vehicles for colon-specific drug delivery may be an efficient approach to improve oral bioavailability of protein and peptide drugs.
authors.affiliation: a Department of Pharmaceutics , China Pharmaceutical University , Nanjing, P.R. China and.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: a Department of Pharmaceutics , China Pharmaceutical University , Nanjing, P.R. China and.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: b School of Pharmacy, Nanchang University , Nanchang, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: b School of Pharmacy, Nanchang University , Nanchang, P.R. China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Zhu
authors.affiliation: b School of Pharmacy, Nanchang University , Nanchang, P.R. China.
authors.forename: Shuangxi
authors.initials: S
authors.lastname: Chen
authors.affiliation: b School of Pharmacy, Nanchang University , Nanchang, P.R. China.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Liu
authors.affiliation: b School of Pharmacy, Nanchang University , Nanchang, P.R. China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Zhong
authors.affiliation: a Department of Pharmaceutics , China Pharmaceutical University , Nanjing, P.R. China and.
authors.forename: Jianping
authors.initials: J
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D013552:Swine; D013667:Technetium / Q000737:chemistry*
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D007328:Insulin; D013667:Technetium; D048271:Chitosan
keywords: Cell-penetrating peptide; Tat; chitosan; insulin; nanoparticles