In vitro and in vivo study of N-trimethyl chitosan nanoparticles for oral protein delivery.
In this study, the effects of alginate modification on absorption properties of FITC-BSA loaded TMC nanoparticles were investigated on an in vitro model of GI epithelium (Caco-2 cells). The feasibility of applying TMC nanoparticles loaded with a model vaccine urease in oral vaccination was also studied. Alginate modified TMC nanoparticles showed higher FITC-BSA permeate efficiency than non-modified TMC nanoparticles. However, alginate modification barely had any effect on TMC nanoparticles' property of decreasing TEER or enhancing drug paracellular transport. Mice s.c. immunized with urease loaded TMC nanoparticles showed highest systematic immune response (IgG levels) but the lowest mucosal response (secretory IgA levels). In the contrast, mice i.g. immunized with urease loaded TMC nanoparticles showed much higher antibody titers of both IgG and secretory IgA than those with urease solution or urease co-administrated with TMC solution. These results indicated that TMC nanoparticles are potential carriers for oral protein and vaccine delivery.
Chen
Fu
F
Key Laboratory of Drug Targeting of Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, PR China.
Zhang
Zhi-Rong
ZR
Yuan
Fang
F
Qin
Xuan
X
Wang
Minting
M
Huang
Yuan
Y
D000284:Administration, Oral; D000464:Alginates; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage; D018938:Caco-2 Cells; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004563:Electrochemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D007114:Immunization; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D011506:Proteins / Q000008:administration & dosage*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000493:pharmacokinetics; D014510:Urease / Q000008:administration & dosage / Q000276:immunology