title: Low molecular weight chitosan in DNA vaccine delivery via mucosa.
abstract: It is acknowledged that low molecular weight chitosan (LMWC) is advantageous over high molecular weight chitosan (HMWC) in the biodegradability. In this report, the potential of LMWC in DNA vaccine delivery via mucosa was evaluated. Firstly, the effects of molecular weight of chitosan on the physicochemical properties and in vitro transfection efficiency of chitosan/DNA polyplexes were investigated. Secondly, the capabilities of the polyplexes based on LMWC to elicit serum IgG antibodies and to attenuate the development of atherosclerosis after intranasal vaccination were compared with the polyplexes based on HMWC in the rabbit model. Finally, the intramucosal transport of the double-labeled polyplexes was observed by confocal microscopy. The results indicated that LMWC had lower binding affinity to DNA and mediated higher transfection efficiency. Intranasal vaccination with LMWC/DNA polyplexes could elicit significant systemic immune responses, modulate the plasma lipoprotein profile and attenuate the progression of atherosclerosis. Those aspects were comparable to those obtained by HMWC/DNA polyplexes. As revealed by confocal images, LMWC/DNA polyplexes remained stable during interaction with the nasal mucosa, and were internalized by nasal epithelial cells, which was similar to the case of HMWC/DNA polyplexes. In conclusion, LMWCs have potential applications in DNA vaccine delivery via mucosa.
authors.affiliation: Institute of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Tong Jia Xiang 24, Nanjing 210009, Jiangsu, People's Republic of China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Yang
authors.forename: Xiying
authors.initials: X
authors.lastname: Yuan
authors.forename: Danning
authors.initials: D
authors.lastname: Cai
authors.forename: Shaoying
authors.initials: S
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Zong
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000276:immunology; D001692:Biological Transport; D048271:Chitosan / Q000737:chemistry*; D018450:Disease Progression; D004337:Drug Carriers / Q000737:chemistry*; D007074:Immunoglobulin G / Q000276:immunology; D008074:Lipoproteins / Q000097:blood; D008297:Male; D018613:Microscopy, Confocal; D008970:Molecular Weight; D009297:Nasal Mucosa / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D007074:Immunoglobulin G; D008074:Lipoproteins; D019444:Vaccines, DNA; D048271:Chitosan