Oral nuclear factor-κB decoy oligonucleotides delivery system with chitosan modified poly(d,l-lactide-co-glycolide) nanospheres for inflammatory bowel disease
2010; Elsevier BV; Volume: 32; Issue: 3 Linguagem: Inglês
10.1016/j.biomaterials.2010.09.034
ISSN1878-5905
AutoresKohei Tahara, Sota Samura, Kaori Tsuji, Hiromitsu Yamamoto, Yusuke Tsukada, Yohei Bando, Hiroyuki Tsujimoto, Ryuichi Morishita, Yoshiaki Kawashimà,
Tópico(s)Microscopic Colitis
ResumoChitosan (CS)-modified poly(D,L-lactide-co-glycolide) (PLGA) nanospheres (NS) were developed and evaluated for use with a nuclear factor kappa B (NF-κB) decoy oligonucleotide (ODN) oral delivery system in an experimental model of ulcerative colitis (UC). Decoy ODN-loaded PLGA NS were prepared by an emulsion solvent diffusion method, and the physicochemical properties of NS were investigated. CS-modified PLGA NS (CS-PLGA NS) showed positive zeta potential, while unmodified PLGA NS (plain-PLGA NS) were negatively charged. Decoy ODN uptake studies with Caco-2 cells using confocal laser scanning microscopy (CLSM) indicated that CS-PLGA NS were more effectively taken up by the cells than plain-PLGA NS. Decoy ODN-loaded CS-PLGA NS were able to improve the stability of ODN against DNase I or an acidic medium, such as gastric juice. Daily oral administration of CS-PLGA NS in a rat model significantly improved dextran sulfate sodium-induced diarrhea, bloody feces, shortening of colon length, and myeloperoxidase activity. Furthermore, decoy ODN-loaded CS-PLGA NS were specifically deposited and adsorbed on the inflamed mucosal tissue of the UC model rat. These results suggested that CS-PLGA NS provide an effective means of colon-specific oral decoy ODN delivery in UC.
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