Skip to main content
Log in

5β-Cholanic Acid/Glycol Chitosan Self-Assembled Nanoparticles (5β-CHA/GC-NPs) for Enhancing the Absorption of FDs and Insulin by Rat Intestinal Membranes

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The absorption-enhancing effects of glycol chitosan modified by 5β-cholanic acid nanoparticles (5β-CHA/GC-NPs) on a drug with poor absorption in the intestine were studied by the method of in situ closed loop. We chose fluorescein isothiocyanate-labeled dextrans (FDs) and insulin as the model drugs. 5β-CHA/GC-NPs loaded to different drugs were prepared by the dialysis method, and the physicochemical characteristics and in vitro release profiles of nanoparticles were also estimated. The results showed that 5β-CHA/GC-NPs markedly increased the absorption of insulin and FDs in the jejunum, ileum, and colon. The ratios of absorption for all the drugs in the jejunum were higher than those in the ileum and colon. In addition, the enhancing effect of 5β-CHA/GC-NPs for the absorption of FDs from the jejunum was decreased with increasing molecular weights. In the toxicity test, 5β-CHA/GC-NPs did not significantly increase the release of protein and the activities of LDH, indicating that the nanoparticles did not cause any membrane damage to the intestine. These findings suggested that 5β-CHA/GC-NPs were safe and useful carriers for enhancing the absorption of the drug with poor absorption by intestinal membranes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Niu Z, Conejos-Sánchez I, Griffin BT, O’Driscoll CM, Alonso MJ. Lipid-based nanocarriers for oral peptide delivery. Adv Drug Deliv Rev. 2016;106(PtB):337–54.

    Article  CAS  Google Scholar 

  2. Yin T, Zhang Y, Liu Y, Chen Q, Fu Y, Liang J, et al. The efficiency and mechanism of N-octyl-O, N-carboxymethyl chitosan-based micelles to enhance the oral absorption of silybin. Int J Pharm. 2017;536(1):231–40.

    Article  Google Scholar 

  3. Arafat M, Kirchhoefer C, Mikov M, Sarfraz M, Löbenberg R. Nanosized liposomes containing bile salt: a vesicular nanocarrier for enhancing oral bioavailability of BCS class III drug. J Pharm Pharm Sci. 2017;20:305–18.

    Article  Google Scholar 

  4. Pooja D, Kulhari H, Kuncha M, Rachamalla SS, Adams DJ, Bansal V, et al. Improving efficacy, oral bioavailability, and delivery of paclitaxel using protein-grafted solid lipid nanoparticles. Mol Pharm. 2016;13(11):3903–12.

    Article  CAS  Google Scholar 

  5. Mooranian A, Negrulj R, Mathavan S, Martinez J, Sciarretta J, Chen-Tan N, et al. An advanced microencapsulated system: a platform for optimized oral delivery of antidiabetic drug-bile acid formulations. Pharm Dev Technol. 2015;20(6):702–9.

    Article  CAS  Google Scholar 

  6. Janes KA, Calvo P, Alonso MJ. Polysaccharide colloidal particles as delivery systems for macromolecules. Adv Drug Deliv Rev. 2001;47:83–97.

    Article  CAS  Google Scholar 

  7. Lehr CM, Bouwstra JA, Schacht E, Junginger HE. In vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers. Int J Pharm. 1992;78:43–8.

    Article  CAS  Google Scholar 

  8. Aspden TJ, Mason JD, Jones NS. Chitosan as a nasal delivery system: the effect of chitosan solutions on in vitro and in vivo mucociliary transport rates in human turbinates and volunteers. J Pharm Sci. 1997;86:509–13.

    Article  CAS  Google Scholar 

  9. Barbari GR, Dorkoosh FA, Amini M, Sharifzadeh M, Atyabi F, Balalaie S, et al. A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides. Int J Nanomedicine. 2017;12:3471–83.

    Article  CAS  Google Scholar 

  10. Hecq J, Siepmann F, Siepmann J, Amighi K, Goole J. Development and evaluation of chitosan and chitosan derivative nanoparticles containing insulin for oral administration. Drug Dev Ind Pharm. 2015;41(12):2037–44.

    Article  CAS  Google Scholar 

  11. Sonaje K, Chuang EY, Lin KJ, Yen TC, Su FY, Tseng MT, et al. Opening of epithelial tight junctions and enhancement of paracellular permeation by chitosan: microscopic, ultrastructural, and computed-tomographic observations. Mol Pharm. 2012;9(5):1271–9.

    Article  CAS  Google Scholar 

  12. Mao HQ, Roy K, Troung-Le VL, Janes KA, Lin KY, Wang Y, et al. Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency. J Control Release. 2001;70:399–421.

    Article  CAS  Google Scholar 

  13. Yinbo P, Chenlu S, Chuanfeng Y, Qige G, Min Y. Low molecular weight chitosan-coated silver nanoparticles are effective for the treatmentof MRSA-infected wounds. Int J Nanomedicine. 2017;12:295–304.

    Google Scholar 

  14. Zeng L, Qin C, Wang W, Chi W, Li W. Absorption and distribution of chitosan in mice after oral administration. Carbohydr Polym. 2008;71:435–40.

    Article  CAS  Google Scholar 

  15. Prego C, Torres D, Fernandez-Megia E, Novoa-Carballal R, Quiñoá E, Alonso MJ. Chitosan–PEG nanocapsules as new carriers for oral peptide delivery. Effect of chitosan pegylation degree. J Control Release. 2006;111(3):299–308.

    Article  CAS  Google Scholar 

  16. Yhee JY, Son S, Kim SH, Park K, Choi K, Kwon IC. Self-assembled glycol chitosan nanoparticles for disease-specific theranostics. J Control Release. 2014;193:202–13.

    Article  CAS  Google Scholar 

  17. Lee SJ, Koo H, Jeong H, Huh MS, Choi Y, Jeong SY, et al. Comparative study of photosensitizer loaded and conjugated glycol chitosan nanoparticles for cancer therapy. J Control Release. 2011;152:21–9.

    Article  CAS  Google Scholar 

  18. Tieshi L, Lara L, Froilan GM, Timothy JM, Yun Y, Anna S. Use of glycol chitosan modified by 5β-cholanic acid nanoparticles for the sustained release of proteins during murine embryonic limb skeletogenesis. J Control Release. 2010;144(1):101–8.

    Article  Google Scholar 

  19. Hyung GJ, Kyung HM, Tae HN, Seong JN, Jae HP, Seo YJ. Prolonged antidiabetic effect of zinc-crystallized insulin loaded glycol chitosan nanoparticles in type 1 diabetic rats. Arch Pharm Res. 2008;31(7):918–23.

    Article  Google Scholar 

  20. Park JH, Cho YW, Chung H, Kwon IC, Jeong SY. Synthesis and characterization of sugar-bearing chitosan derivatives: aqueous solubility and biodegradability. Biomacromolecules. 2003;4(4):1087–91.

    Article  CAS  Google Scholar 

  21. Zheng Y, Wu Y, Yang W, Wang C, Fu S, Shen X. Preparation, characterization, and drug release in vitro of chitosan-glycyrrhetic acid nanoparticles. J Pharm Sci. 2005;95(1):181–91.

    Article  Google Scholar 

  22. Farnaz E, Mohammad HG, Behnaz E, Mohammad RK, Fatemeh A, Rassoul D. PLGA nanoparticles of different surface properties: preparation and evaluation of their body distribution. Int J Pharmaceut. 2008;349(1):249–55.

    Google Scholar 

  23. Fetih G, Habib F, Okada N, Fujita T, Attia M, Yamamoto A. Nitricoxide donors can enhance the intestinal transport and absorption of insulin and [Asu1,7]-eel calcitonin in rats. J Control Release. 2005;106:287–97.

    Article  CAS  Google Scholar 

  24. Chengyun Y, Jiwei G, Yuguang L, Weiguo S, Hongying J. Improved intestinal absorption of water-soluble drugs by acetylation of G2 PAMAM dendrimer nanocomplexes in rat. Drug Deliv Transl Res. 2017;7:408–15.

    Article  Google Scholar 

  25. Koo H, Min KH, Lee SC, Park JH, Park K, Jeong SY, et al. Enhanced drug-loading and therapeutic efficacy of hydrotropic oligomer-conjugated glycol chitosan nanoparticles for tumor-targeted paclitaxel delivery. J Control Release. 2013;172:823–31.

    Article  CAS  Google Scholar 

  26. Lamprecht A, Schafer U, Lehr CM. Size-dependent bioadhesion of micro- and nanoparticulate carriers to the inflamed colonic mucosa. Pharm Res. 2001;18:788–93.

    Article  CAS  Google Scholar 

  27. Kim JH, Kim YS, Kim S, Park JH, Kim K, Choi K, et al. Hydrophobically modified glycol chitosan nanoparticles as carriers for paclitaxel. J Control Release. 2006;111:228–34.

    Article  CAS  Google Scholar 

  28. Kwon S, Park JH, Chung H, Kwon IC, Jeong SY. Physicochemical characteristics of self-assembled nanoparticles based on glycol chitosan bearing 5-cholanic acid. Langmuir. 2003;19(24):10188–93.

    Article  CAS  Google Scholar 

  29. Takeuchi H, Yamamoto H, Kawashima Y. Mucoadhesive nanoparticulate systems for peptide drug delivery. Adv Drug Deliv Rev. 2001;47:39–55.

    Article  CAS  Google Scholar 

  30. Takeuchi H, Matsui Y, Yamamoto H, Kawashima Y. Mucoadhesive liposomes coated with chitosan or carbopol for oral administration of peptide drugs. In: Proceedings of 26th international symposiumon controlled release of bioactive materials; 1999. p. 988–9.

    Google Scholar 

  31. Park JH, Kwon S, Nam JO, Park RW, Chung H, Seo SB, et al. Self-assembled nanoparticles based on glycol chitosan bearing 5beta-cholanic acid for RGD peptide delivery. J Control Release. 2004;95:579–88.

    Article  CAS  Google Scholar 

  32. Kim JH, Kim YS, Park K, Kang E, Lee S, Nam HY, et al. Self-assembled glycol chitosan nanoparticles for the sustained and prolonged delivery of antiangiogenic small peptide drugs in cancer therapy. Biomaterials. 2008;29:1920–30.

    Article  CAS  Google Scholar 

  33. Yuan Z, Ye Y, Gao F, Yuan H, Lan M, Lou K, et al. Chitosan-graft-β-cyclodextrin nanoparticles as a carrier for controlled drug release. Int J Pharm. 2013;446:191–8.

    Article  CAS  Google Scholar 

  34. Park K, Hong HY, Moon HJ, Lee BH, Kim IS, Kwon IC, et al. A new atherosclerotic lesion probe based on hydrophobically modified chitosan nanoparticles functionalized by the atherosclerotic plaque targeted peptides. J Control Release. 2008;128(3):217–23.

    Article  CAS  Google Scholar 

  35. Yamabe K, Kato Y, Onishi H, Machida Y. Potentiality of double liposomes containing salmon calcitonin as an oral dosage form. J Control Release. 2003;20:429–36.

    Article  Google Scholar 

  36. Lee VHL, Yamamoto A, Kompella UB. Mucosal penetration enhancers for facilitation of peptide and protein drug absorption. Crit Rev Ther Drug Carrier Syst. 1991;8:91–2.

    CAS  PubMed  Google Scholar 

Download references

Funding

We sincerely thank the National Natural Science Foundation of China (No. 31860266) and the Program of GuangXi Provincial Natural Science Foundation of China (No. 2018JJA140093) for the financial support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chengyun Yan.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yan, C., Gu, J., Lv, Y. et al. 5β-Cholanic Acid/Glycol Chitosan Self-Assembled Nanoparticles (5β-CHA/GC-NPs) for Enhancing the Absorption of FDs and Insulin by Rat Intestinal Membranes. AAPS PharmSciTech 20, 30 (2019). https://doi.org/10.1208/s12249-018-1242-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-018-1242-6

KEY WORDS

Navigation