title: Preparation and evaluation of lectin-conjugated PLGA nanoparticles for oral delivery of thymopentin.
abstract: The purpose of this study was to design and evaluate lectin-conjugated PLGA nanoparticles for oral delivery of thymopentin. Thymopentin loaded PLGA nanoparticles (TP5-NPs) were prepared by a double emulsion-solvent evaporation technique. Novel WGA-PLGA conjugates were synthesized by coupling the amino groups of wheat germ agglutinin (WGA) to the carbodiimide-activated carboxylic groups of PLGA, and were incorporated into nanoparticles preparation to take mucoadhesive properties. Important characteristics such as particle size, zeta potential, entrapment efficiency, storage stability, as well as in vitro drug release behavior were investigated. The retention of biorecognitive activity of WGA after covalent coupling was confirmed by haemagglutination test. In vitro experiments with pig mucin (PM) demonstrated that the conjugation of WGA enhanced the interaction about 1.8-4.2 fold compared with that of the non-conjugated nanoparticles, and still exhibited sugar specificity. The pharmacodynamical studies on oral administration of WGA-TP5-NPs were performed in FACScan flow cytometry. The values of CD4(+)/CD8(+) ratios were significantly increased compared with that of TP5-NPs (p<0.01). The enhanced uptake was related to the increasing of WGA content on nanoparticles. These results confirmed that the conjugation of WGA onto PLGA nanoparticles effectively improved the intestinal absorption of TP5 due to specific bioadhesion on GI cell membrane.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, China. yinyashu@sina.com
authors.forename: Yashu
authors.initials: Y
authors.lastname: Yin
authors.forename: Dawei
authors.initials: D
authors.lastname: Chen
authors.forename: Mingxi
authors.initials: M
authors.lastname: Qiao
authors.forename: Zhe
authors.initials: Z
authors.lastname: Lu
authors.forename: Haiyang
authors.initials: H
authors.lastname: Hu
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D004912:Erythrocytes / Q000187:drug effects; D005434:Flow Cytometry; D006386:Hemagglutination Tests; D007108:Immune Tolerance / Q000187:drug effects; D019344:Lactic Acid / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D037121:Plant Lectins / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties; D016305:Thymopentin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D037121:Plant Lectins; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016305:Thymopentin