title: Targeted delivery of chitosan nanoparticles to Peyer's patch using M cell-homing peptide selected by phage display technique.
abstract: This study is aimed to develop an efficient oral vaccine carrier which specifically targets the follicle-associated epithelium region of Peyer's patch (PP). M cell-homing peptide was selected by the phase display technique and its targeting efficiency was validated using chitosan nanoparticles (CNs) conjugated with the discovered peptide. A phage clone encoding CKSTHPLSC (CKS9) peptide sequence was selected by analysis of comparative superiority in transcytosis efficacy across the M cell layer in vitro and in vivo among the candidates. CKS9 was chemically conjugated to water-soluble chitosan (WSC) and the CKS9-immobilized chitosan nanoparticles (CKS9-CNs) were prepared by ionic gelation of CKS9-WSC with tripolyphosphate, yielding spherical nanoparticles around 226.2 +/- 41.9 nm. The targeting ability of CKS9-CNs to the M cell and to the PP regions of rat small intestine was investigated by in vitro transcytosis assay and closed ileal loop assay, respectively, and was visualized by fluorescence-microscopy analysis. CKS9-CNs were transported more effectively across the M cell model and accumulated more specifically into PP regions in comparison with CNs, indicating that CKS9 peptide prominently enhanced the targeting and transcytosis ability of CNs to PP regions. These results suggest that the CKS9-CNs could be used as a new carrier for oral vaccine delivery.
authors.affiliation: School of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
authors.forename: Mi-Kyong
authors.initials: MK
authors.lastname: Yoo
authors.forename: Sang-Kee
authors.initials: SK
authors.lastname: Kang
authors.forename: Jin-Huk
authors.initials: JH
authors.lastname: Choi
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Park
authors.forename: Hee-Sam
authors.initials: HS
authors.lastname: Na
authors.forename: Hyun-Chul
authors.initials: HC
authors.lastname: Lee
authors.forename: Eun-Bae
authors.initials: EB
authors.lastname: Kim
authors.forename: Nam-Kyung
authors.initials: NK
authors.lastname: Lee
authors.forename: Jae-Woon
authors.initials: JW
authors.lastname: Nah
authors.forename: Yun-Jaie
authors.initials: YJ
authors.lastname: Choi
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002460:Cell Line; D048271:Chitosan / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008422:Materials Testing; D008969:Molecular Sequence Data; D015394:Molecular Structure; D053758:Nanoparticles; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D019151:Peptide Library; D010581:Peyer's Patches / Q000378:metabolism*; D051381:Rats
chemical_list: D004337:Drug Carriers; D005136:Eye Proteins; D010446:Peptide Fragments; D019151:Peptide Library; C052615:peptide M, retinal S antigen; D048271:Chitosan