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

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• 作者：Yan Zhang ; Xia Lin ; Xuli Du ; Sicong Geng ; Hongren Li…
• 关键词：Mucoadhesive nanoparticles ; pH ; sensitive ; Thiolated polymers ; Permeation enhancing ; Oral drug delivery ; Nanomedicine
• 刊名：Journal of Nanoparticle Research
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：17
• 期：2
• 全文大小：899 KB
• 参考文献：1. Attivi D, Werhle P, Maincent P et al (2005) Formulation of insulin-loaded polymeric nanoparticles using response surface methodology. Drug Dev Ind Pharm 31:179-89 CrossRef
  2. Bakhru SH, Furtado S, Morello AP et al (2013) Oral delivery of proteins by biodegradable nanoparticles. Adv Drug Deliv Rev 65:811-21 CrossRef
  3. 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 94:177-86 CrossRef
  4. Chen MC, Sonaje K, Sung HW et al (2011) A review of the prospects for polymeric nanoparticle platforms in oral insulin delivery. Biomaterials 32:9826-838 CrossRef
  5. Clausen A, Kast C, Bernkop-Schnurch A (2002) The role of glutathione in the permeation enhancing effect of thiolated polymers. Pharm Res 19:602-08 CrossRef
  6. 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 439:136-44 CrossRef
  7. Desai M, Labhasetwar V, Levy R et al (1996) Gastrointestinal uptake of biodegradable microparticles: effect of particle size. Pharm Res 13:1838-845 CrossRef
  8. Ensign LM, Cone R, Hanes J (2012) Oral drug delivery with polymeric nanoparticles: The gastrointestinal mucus barriers. Adv Drug Deliv Rev 64:557-70 CrossRef
  9. Felber AE, Dufresne MH, Leroux JC (2012) pH-sensitive vesicles, polymeric micelles, and nanospheres prepared with polycarboxylates. Adv Drug Deliv Rev 64:979-92 CrossRef
  10. 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 65:800-10 CrossRef
  11. Ganguly K, Chaturvedi K, Aminabhavi TM et al (2014) Polysaccharide-based micro/nanohydrogels for delivering macromolecular therapeutics. J Control Release 193:162-73 CrossRef
  12. George M, Abraham TE (2006) Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan—a review. J Control Release 114:1-4 CrossRef
  13. 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 7:1311-337 CrossRef
  14. 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 5:77-5 CrossRef
  15. Lai SK, Wang YY, Hanes J (2009) Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev 61:158-71 CrossRef
  16. 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 329:182-91 CrossRef
  17. 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 6:1104-112
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Nanotechnology
  Inorganic Chemistry
  Characterization and Evaluation Materials
  Physical Chemistry
  Applied Optics, Optoelectronics and Optical Devices
  
• 出版者：Springer Netherlands
• ISSN：1572-896X

文摘

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.