title: Improved intestinal absorption of water-soluble drugs by acetylation of G2 PAMAM dendrimer nanocomplexes in rat.
abstract: In search of an effective and less toxic absorption enhancer, we synthesized primary amine acetylation of generation 2 polyamidoamine (G2 PAMAM) dendrimer (Ac-G2) by the reaction of G2 PAMAM dendrimer with acetic anhydride, and evaluated the effects of Ac-G2 on the intestinal absorption of poorly absorbable water-soluble drugs using an in situ closed-loop method in rats. The results indicated that Ac50-G2 had a greatest absorption enhancing effect for 5(6)-carboxyfluorescein (CF) in various acetylation levels of G2 PAMAM dendrimers. Ac50-G2 with various concentrations (0.1-1.0%, w/v) could significantly improve the intestinal absorption of alendronate, CF, and fluorescein isothiocyanate-labeled dextrans (FD4), although they did not enhance the absorption of macromolecular drug of FD10, and the absorption enhancement effect of Ac50-G2 was concentration-dependent. Furthermore, we examined the intestinal membrane damage with or without Ac50-G2. The results displayed Ac50-G2 at lower concentrations (0.1-0.5%, w/v) did not cause any observed toxic effect to the intestinal membranes. These findings suggested Ac50-G2 at lower concentrations (below 0.5%, w/v) might be promising as an effective and safe absorption enhancers to promote the intestinal absorption of poorly absorbable drugs.
authors.affiliation: College of Pharmacy|, Guilin Medical University, Guilin,, 541004, China. hademan@126.com.|First Affiliated Hospital of Jiamusi University, Jiamusi University, Jiamusi, 154000, China. hademan@126.com.
authors.forename: Chengyun
authors.initials: C
authors.lastname: Yan
authors.affiliation: First Affiliated Hospital of Jiamusi University, Jiamusi University, Jiamusi, 154000, China.
authors.forename: Jiwei
authors.initials: J
authors.lastname: Gu
authors.affiliation: College of Pharmacy, Jiamusi University, Jiamusi, 154000, China.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Lv
authors.affiliation: College of Pharmacy, Jiamusi University, Jiamusi, 154000, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Shi
authors.affiliation: First Affiliated Hospital of Jiamusi University, Jiamusi University, Jiamusi, 154000, China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Jing
mesh_terms: D000089:Acetic Anhydrides / Q000737:chemistry*; D000107:Acetylation; D019386:Alendronate / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D050091:Dendrimers / Q000008:administration & dosage* / Q000737:chemistry; D003911:Dextrans / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005452:Fluoresceins / Q000008:administration & dosage / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017208:Rats, Wistar; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000089:Acetic Anhydrides; D050091:Dendrimers; D003911:Dextrans; D005452:Fluoresceins; D005456:Fluorescent Dyes; C104700:PAMAM Starburst; C015219:fluorescein isothiocyanate dextran; D014867:Water; C031800:acetic anhydride; C024098:6-carboxyfluorescein; D016650:Fluorescein-5-isothiocyanate; D019386:Alendronate
keywords: Absorption enhancer; Acetylation modification; G2 PAMAM dendrimer; Intestinal absorption; Poorly absorbable drugs