Identification of a peptide sequence that improves transport of macromolecules across the intestinal mucosal barrier targeting goblet cells

Kang, Soo‐Kyung; Woo, Jeong Soo; Kim, Minkook; Woo, Sang Ho; Choi, Jin Hyuk; Lee, Hong Gu; Lee, Nam Kyung; Choi, Yun Jaie

doi:10.1016/j.jbiotec.2008.01.021

Cited by 72 publications

(53 citation statements)

References 18 publications

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“…This is supported by the fact that we found transcytosis into lymph occurring within 30 min after intestinal delivery of selected library phage. Rapid transportation of library phage was previously observed in a study in rats in which phage were recovered from tissues such as spleen, liver or kidney soon after injection into the jejunum 21 . Taken together these results provide strong evidence that our panning procedure resulted in the selection of specific transcytosis reagents.…”

Section: Determination Of Systemic Delivery Of a 13c -Protein Constructmentioning

confidence: 78%

“…Consequently we used 13C in follow up mouse studies to confirm the efficacy of the trans-mucosal delivery of proteins in a second animal model. Interestingly a phage display study in rats identified a nine amino acid long peptide (CSK; CSKSSDYQC) which increased uptake via the intestinal mucosa 21 . Our peptide 13C and CSK share some sequence similarities, notably the presence of a ser-ser motif.…”

Section: Determination Of Systemic Delivery Of a 13c -Protein Constructmentioning

confidence: 99%

“…For example, gastrointestinal administration of proteins, in the absence of adjuvants, preferentially induces immunological tolerance ("oral tolerance") 1 , but adjuvant-including enteric vaccines are superior in inducing IgA responses which are important to prevent infections with 4 targeting [13][14][15] and receptor identification 16,17 . Extensive screening of phage display libraries has also been used to identify ligands that facilitate translocation across the mucosa of the gastrointestinal tract 18 or binding to and transport via M cells 19,20 or goblet cells 21,22 .…”

Section: Introductionmentioning

confidence: 99%

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Identification of Targeting Peptides for Mucosal Delivery in Sheep and Mice

et al. 2015

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In this study we identified and characterized a novel cyclic peptide that facilitates the rapid transportation of conjugated molecules across the epithelial layer of the small intestine. The peptide was initially selected from phage display libraries using a large animal experimental model which employed consecutive in vitro and in vivo panning. The procedure was designed to enrich for peptides that facilitated transcytosis across the intestinal epithelium into the intestinal afferent lymphatic system. A small set of peptides was repeatedly isolated using this selection method, 2 however the cyclic nonamer CTANSSAQC, 13C dominated. The activity of the putative targeting peptide C13 was then verified using a mouse model. These experiments showed that the 13C peptide as well as macromolecules conjugated to it were rapidly transported across the intestinal mucosa into distinct subsets of epithelial cells and CD11+ cells located in the lamina propria and Peyer's Patches. Significant amounts of intact protein could be delivered into the systemic circulation after rectal and nasal application. Thus, peptide 13C is regarded as an attractive carrier candidate for mucosal delivery of large molecules. The preferential targeting to distinct intestinal cells may be utilized to deliver active biological drugs for the effective control of diseases of the gut.

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Section: Determination Of Systemic Delivery Of a 13c -Protein Constructmentioning

confidence: 78%

Section: Determination Of Systemic Delivery Of a 13c -Protein Constructmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of Targeting Peptides for Mucosal Delivery in Sheep and Mice

et al. 2015

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“…Chen et al identified a peptide, TD-1 (AC-SSSPS-KH-CG), based on in vivo phage display on mouse skin (17). In another study, Kang et al identified a sequence C-SKSSDYQ-C that enhances oral absorption after oral delivery of the phage library (30). More recently, Morris et al studied translocation of phage library in alveolar epithelial cultures and identified a sequence C-TSGTHPR-C that enables translocation (31).…”

Section: Discussionmentioning

confidence: 99%

Delivery of siRNA and other macromolecules into skin and cells using a peptide enhancer

Hsu

Mitragotri

2011

Proc. Natl. Acad. Sci. U.S.A.

189

143

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Delivery of macromolecules into cells and tissues such as skin is a major challenge. This obstacle poses a particular challenge for the delivery of siRNA where cellular and tissue level transport barriers need to be overcome. siRNAs are potential therapeutics for various dermatological diseases including psoriasis, atopic dermatitis, and cancer; however, their utility is limited by their low absorption across the stratum corneum (SC) and into viable cells of skin. Here, we address this challenge using a peptide identified by phage display termed skin penetrating and cell entering (SPACE) peptide. In vitro studies indicated that the SPACE peptide, when conjugated to cargoes such as small molecules and proteins, was able to facilitate their penetration across the SC into epidermis and dermis. The peptide also exhibited increased penetration into various cells including keratinocytes, fibroblasts, and endothelial cells, likely through a macropinocytosis pathway. The ability of SPACE peptide to deliver siRNA was tested in vivo using two targets, interleukin-10 and GAPDH. Conjugation of the peptide to siRNA led to their enhanced absorption into skin and knockdown of corresponding protein targets.

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“…However, the M cells account for only small number of intestinal cells and the targeting ligands usually were used to transport vaccine, thus limits their application. Apart from the M cells, goblet cells have also been studied as potential targets for oral drug delivery (Kang et al, 2008). Our group recently reported a goblet cell-targeting NPs by conjugating N-trimethyl chitosan chloride (TMC) with CSKSSDYQC peptide, which specifically recognized goblet cells and posed a preferable hypoglycemic effect as compared with the unmodified ones (Jin et al, 2012;Zhang et al, 2014b), whereas goblet cells account for only 12% of intestinal cells.…”

Section: Introductionmentioning

confidence: 99%

A novel ligand conjugated nanoparticles for oral insulin delivery

et al. 2015

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In order to enhance the interaction between nanocarrier and gastrointestinal epithelial cells, we developed nanoparticles (NPs) modified with targeting ligand FQSIYPpIK (FQS), which specifically interact with integrin avb3 receptor expressing on the intestinal epithelium. The targeting NPs were prepared by coating the insulin-loaded poly(lactide-co-glycolide)-monomethoxy-poly(polyethylene glycol) micelle cores with FQS modified trimethyl chitosan chloride. In in vitro study, the fabricated NPs showed ameliorated drug release profile and improved enzymatic stability compared with micelles alone. In the integrin avb3 receptor over-expressed Caco-2 cells model, FQS modified NPs exhibited significantly accelerated intracellular uptake due to the active ligand-receptor mediation. Meanwhile, the targeting NPs also showed enhanced transport across the Caco-2 monolayer cells via both transcellular and paracellular pathways. Besides, orally administered FQS modified NPs produced a prominent hypoglycemic response and an increase of the serum insulin concentration in diabetic rats. Both in vitro and in vivo results demonstrated the FQS peptide modified NPs as promising intestinal cell-targeting nanocarriers for efficient oral delivery of insulin.

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Identification of a peptide sequence that improves transport of macromolecules across the intestinal mucosal barrier targeting goblet cells

Cited by 72 publications

References 18 publications

Identification of Targeting Peptides for Mucosal Delivery in Sheep and Mice

Identification of Targeting Peptides for Mucosal Delivery in Sheep and Mice

Delivery of siRNA and other macromolecules into skin and cells using a peptide enhancer

A novel ligand conjugated nanoparticles for oral insulin delivery

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