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Journal of Nanoparticle Research

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01-02-2015 | Research Paper

pH-sensitive thiolated nanoparticles facilitate the oral delivery of insulin in vitro and in vivo

Authors: Yan Zhang, Xia Lin, Xuli Du, Sicong Geng, Hongren Li, Hong Sun, Xing Tang, Wei Xiao

Published in: Journal of Nanoparticle Research | Issue 2/2015

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Abstract

In this work, we designed and developed a delivery system composed of enteric Eudragit L100-cysteine/reduced glutathione nanoparticles (Eul-cys/GSH NPs) for oral delivery of insulin. First, interactions between Eul-cys and mucin glycoproteins, which are believed to be the result of disulfide bonds, were confirmed using rheology experiments. Subsequently, the insulin-loaded Eul-cys/GSH NPs were prepared by the diffusion method using the rich gel network multipore structure at the surface of the Eul-cys when the pH was higher than the pKa of Eul-cys polymer. The Eul-cys/GSH NPs obtained were characterized by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. The results obtained showed that the average particle size ranged from 240 to 280 nm, and the particles were almost spherical in shape. The in vitro drug release results showed that the Eul-cys/GSH NPs retained a large amount of insulin in simulated gastric fluid, while a significant insulin release was found in simulated intestinal fluid. The in situ release study suggested that NPs released a greater amount of FITC-insulin (49.2 %) into the intestinal mucus layer compared with that of FITC-insulin solution (16.4 %), which facilitating insulin delivery through the intestinal mucosa. Eul-cys/GSH NPs exhibited promising mucoadhesive properties demonstrated using an in vitro cell model. Consequently, NPs were introduced into the ileum loop of healthy rats, thus enhancing the intestinal absorption of insulin and providing a prolonged reduction in blood glucose levels. These results suggest that Eul-cys/GSH NPs may be a promising delivery system for the treatment of diabetes.

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Attivi D, Werhle P, Maincent P et al (2005) Formulation of insulin-loaded polymeric nanoparticles using response surface methodology. Drug Dev Ind Pharm 31:179–189CrossRef

Bakhru SH, Furtado S, Morello AP et al (2013) Oral delivery of proteins by biodegradable nanoparticles. Adv Drug Deliv Rev 65:811–821CrossRef

Bernkop-Schnurch A, Guggi D, Pinter Y (2004) Thiolated chitosans: development and in vitro evaluation of a mucoadhesive, permeation enhancing oral drug delivery system. J Control Release 94:177–186CrossRef

Chen MC, Sonaje K, Sung HW et al (2011) A review of the prospects for polymeric nanoparticle platforms in oral insulin delivery. Biomaterials 32:9826–9838CrossRef

Clausen A, Kast C, Bernkop-Schnurch A (2002) The role of glutathione in the permeation enhancing effect of thiolated polymers. Pharm Res 19:602–608CrossRef

Deat-Laine E, Hoffart V, Beyssac E et al (2012) Development and in vitro characterization of insulin loaded whey protein and alginate microparticles. Inter J Pharm 439:136–144CrossRef

Desai M, Labhasetwar V, Levy R et al (1996) Gastrointestinal uptake of biodegradable microparticles: effect of particle size. Pharm Res 13:1838–1845CrossRef

Ensign LM, Cone R, Hanes J (2012) Oral drug delivery with polymeric nanoparticles: The gastrointestinal mucus barriers. Adv Drug Deliv Rev 64:557–570CrossRef

Felber AE, Dufresne MH, Leroux JC (2012) pH-sensitive vesicles, polymeric micelles, and nanospheres prepared with polycarboxylates. Adv Drug Deliv Rev 64:979–992CrossRef

Gamboa JM, Leong KW et al (2013) In vitro and in vivo models for the study of oral delivery of nanoparticles. Adv Drug Deliv Rev 65:800–810CrossRef

Ganguly K, Chaturvedi K, Aminabhavi TM et al (2014) Polysaccharide-based micro/nanohydrogels for delivering macromolecular therapeutics. J Control Release 193:162–173CrossRef

George M, Abraham TE (2006) Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan—a review. J Control Release 114:1–14CrossRef

Jain S, Rathi VV, Godugu C et al (2012) Folate-decorated PLGA nanoparticles as a rationally designed vehicle for the oral delivery of insulin. Nanomedicine 7:1311–1337CrossRef

Kawashima Y, Yamamoto H, Kuno Y et al (2000) Mucoadhesive DL-lactide/glycolide copolymer nanospheres coated with chitosan to improve oral delivery of elcatonin. Pharm Dev Technol 5:77–85CrossRef

Lai SK, Wang YY, Hanes J (2009) Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev 61:158–171CrossRef

Li M, Lu W, Zhang Q et al (2007) Distribution, transition, adhesion and release of insulin loaded nanoparticles in the gut of rats. Int J Pharm 329:182–191CrossRef

Lin YH, Chung CK, Sung HW et al (2005) Preparation of nanoparticles composed of chitosan/poly-γ-glutamic acid and evaluation of their permeability through Caco-2 cells. Biomacromolecules 6:1104–1112CrossRef

Liu Y, Kong M, Chen XG et al (2013) Biocompatibility, cellular uptake and biodistribution of the polymeric amphiphilic nanoparticles as oral drug carriers. Colloids Surf B 103:345–353CrossRef

Lopes MA, Abrahim BA, Ribeiro AJ et al (2014) Intestinal absorption of insulin nanoparticles: Contribution of M cells. Nanomedicine 10:1139–1151CrossRef

Makhlof A, Tozuka Y, Takeuchi H (2011) Design and evaluation of novel pH-sensitive chitosan nanoparticles for oral insulin delivery. Eur J Pharm Sci 42:445–451CrossRef

Morishita M, Goto T, Lowman AM et al (2004) Mucosal insulin delivery systems based on complexation polymer hydrogels: effect of particle size on insulin enteral absorption. J Control Release 97:115–124CrossRef

Mundargi RC, Rangaswamy V, Aminabhavi TM (2011) pH-Sensitive oral insulin delivery systems using Eudragit microspheres. Drug Dev Ind Pharm 37:977–985CrossRef

Nakamura K, Murray RJ, Lowman AM (2004) Oral insulin delivery using P(MAA-g-EG) hydrogels: effects of network morphology on insulin delivery characteristics. J Control Release 95:589–599CrossRef

Su FY, Lin KJ, Sung HW et al (2012) Protease inhibition and absorption enhancement by functional nanoparticles for effective oral insulin delivery. Biomaterials 33:2801–2811CrossRef

Takeuchi H, Yamamoto H, Kawashima Y (2001) Mucoadhesive nanoparticulate systems for peptide drug delivery. Adv Drug Deliv Rev 47:39–54CrossRef

Woitiski CB, Sarmento B, Veiga F (2011) Facilitated nanoscale delivery of insulin across intestinal membrane models. Int J Pharm 412:123–131CrossRef

Xiong XY, Li QH, Gong YC et al (2013) Pluronic P85/poly(lactic acid) vesicles as novel carrier for oral insulin delivery. Colloids Surf B 111:282–288CrossRef

Yang Y, Wang SP, Chen MW et al (2014) Advances in self-assembled chitosan nanomaterials for drug delivery. Biotechnol Adv 32:1301–1316CrossRef

Zhang Y, Du X, Tang X et al (2014) Thiolated Eudragit based nanoparticles for oral insulin delivery: preparation, characterization, and evaluation using intestinal epithelial cells in vitro. Macromol Biosci 14:842–852

Zhang Y, Wu X, Tang X et al (2012) Thiolated Eudragit nanoparticles for oral insulin delivery: preparation, characterization and in vivo evaluation. Int J Pharm 436:341–350CrossRef

Zhao X, Shan C, Li R et al (2013) Preparation, characterization, and evaluation in vivo of Ins-SiO2-HP55 (insulin-loaded silica coating HP55) for oral delivery of insulin. Int J Pharm 454:278–284CrossRef

Title: pH-sensitive thiolated nanoparticles facilitate the oral delivery of insulin in vitro and in vivo
Authors: Yan Zhang
Xia Lin
Xuli Du
Sicong Geng
Hongren Li
Hong Sun
Xing Tang
Wei Xiao
Publication date: 01-02-2015
Publisher: Springer Netherlands
Published in: Journal of Nanoparticle Research / Issue 2/2015
Print ISSN: 1388-0764
Electronic ISSN: 1572-896X
DOI: https://doi.org/10.1007/s11051-014-2847-7

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