Advertisement

Journal of Pharmaceutical Investigation

, Volume 49, Issue 1, pp 37–44 | Cite as

Potential of different salt forming agents on the formation of chitosan nanoparticles as carriers for protein drug delivery systems

  • Manee Luangtana-anan
  • Jurairat Nunthanid
  • Sontaya Limmatvapirat
Original Article
  • 95 Downloads

Abstract

The effects of salt forming agents for chitosan on the potential for nanoparticle formation was investigated. The salt forms were prepared from the amino acid group, including glutamic and aspartic acids, and the alpha hydroxyl acid group, including lactic and glycolic acids. All types of chitosan salt could be used to prepare bovine serum albumin (BSA) loaded nanoparticles. The chitosan salts prepared from the amino acid group showed a higher salt formation ability as demonstrated using FTIR, hence a higher %encapsulation efficiency (%EE) and a reduction in zeta potential were obtained. The difference was due to the different organic acids used giving different polymer conformations and pH values in solution. Chitosan glutamate gave the highest salt formation ability and hence the highest %EE was obtained. The release of protein from all types of chitosan was similar and chitosan glutamate exhibited the highest release. Chitosan salt is therefore a material of choice for protein-loaded nanoparticles and the characteristics of nanoparticles can be readily modulated by different types of salt form.

Keywords

Chitosan salt Chitosan nanoparticle Protein Amino acid and alpha-hydroxyl acid 

Notes

Acknowledgements

This work was supported by the Research and Development Institute of Silpakorn University. This project would have been impossible without the facilities provided by the Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

References

  1. Agnihotri S, Mallikarjuna N, Aminabhavi T (2004) Recent advances on chitosan-based micro and nanoparticles in drug delivery. J Control Release 100:5–28CrossRefGoogle Scholar
  2. Ahsan F, Rivas IP, Khan MA, Torres Suárez AI (2002) Targeting to macrophages: role of physicochemical properties of particulate carriers—liposomes and microspheres—on the phagocytosis by macrophages. J Control Release 79(1):29–40CrossRefGoogle Scholar
  3. Boonsongrit Y, Mueller BW, Mitrevej A (2008) Characterization of drug-chitosan interaction by 1H NMR, FTIR and isothermal titration calorimetry. Eur J Pharm Sci 69(1):388–395Google Scholar
  4. Calvo P, Remuñan-López C, Vila-Jato JL, Alonso MJ (1997) Novel hydrophilic chitosan-polyethylene oxide nanoparticles as protein carriers. Pharm Res 14:1431–1436CrossRefGoogle Scholar
  5. Casettari L, Illum L (2014) Chitosan in nasal delivery systems for therapeutic drugs. J Control Release 190:189–200CrossRefGoogle Scholar
  6. Chen F, Zhang ZR, Huang Y (2007) Evaluation and modification of N-trimethyl chitosan chloride nanoparticles as protein carriers. Int J Pharm 336:166–173CrossRefGoogle Scholar
  7. Douglas KL, Piccirillo CA, Tabrizian M (2006) Effects of alginate inclusion on the vector properties of chitosan-based nanoparticles. J Control Release 115:354–361CrossRefGoogle Scholar
  8. Gan Q, Wang T (2007) Chitosan nanoparticle as protein delivery carrier-systematic examination of fabrication conditions for efficient loading and release. Colloid Surf B 59:24–34CrossRefGoogle Scholar
  9. Gan Q, Wang T, Cochrane C, McCarron P (2005) Modulation of surface charge, particle size and morphological properties of chitosan-TPP nanoparticles intended for gene delivery. Colloid Surf B 44:65–73CrossRefGoogle Scholar
  10. George M, Abraham TE (2006) Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan: a review. J Control Release 114:1–14CrossRefGoogle Scholar
  11. Graves RA, Ledet GA, Glotser EY, Mitchner DM, Bostanian LA, Mandal TK (2015) Formulation and evaluation of biodegradable nanoparticles for the oral delivery of fenretinide. Eur J Pharm Sci 76:1–9CrossRefGoogle Scholar
  12. He B, Ge J, Yue P, Yue X, Fu R, Liang J, Gao X (2017) Loading of anthocyanins on chitosan nanoparticles influences anthocyanin degradation in gastrointestinal fluids and stability in a beverage. Food Chem 221:1671–1677CrossRefGoogle Scholar
  13. Hejazi R, Amiji M (2003) Chitosan-based gastrointestinal delivery systems. J Control Release 89:151–165CrossRefGoogle Scholar
  14. Huanbutta K, Cheewatanakornkool K, Terada K, Nunthanid J, Sriamornsak P (2013) Impact of salt form and molecular weight of chitosan on swelling and drug release from chitosan matrix tablets. Carbohydr Polym 97(1):26–33CrossRefGoogle Scholar
  15. Huang GQ, Cheng LY, Xiao JX, Xiao-Na Han (2015) Preparation and characterization of O-carboxymethyl chitosan–sodium alginate polyelectrolyte complexes. Colloid Polym Sci 293:401–407CrossRefGoogle Scholar
  16. Ilium L (1998) Chitosan and its use as a pharmaceutical excipient. Pharm Res 15:1326–1331CrossRefGoogle Scholar
  17. Jung T, Kamm W, Breitenbach A, Xiao JX, Kissel T (2000) Biodegradable nanoparticles for oral delivery of peptides: is there a role for polymers to affect mucosal uptake. Eur J Pharm Biopharm 50(1):147–160CrossRefGoogle Scholar
  18. Ko JA, Park HJ, Hwang SJ, Lee JS (2002) Preparation and characterization of chitosan microparticles intended for controlled drug delivery. Int J Pharm 249:165–174CrossRefGoogle Scholar
  19. Kraisit P, Limmatvapirat S, Nunthanid J, Sriamornsak P, Luangtana-anan M (2013) Nanoparticle formation by using shellac and chitosan for a protein delivery system. Pharm Dev Technol 18(3):686–693CrossRefGoogle Scholar
  20. Lim ST, Martin GP, Berry DJ, Brown MB (2000) Preparation and evaluation of the in vitro drug release properties and mucoadhesion of novel microspheres of hyaluronic acid and chitosan. J Control Release 66(2):281–292CrossRefGoogle Scholar
  21. Limmatvapirat S, Limmatvapirat C, Puttipipatkhachorn S, Nuntanid J, Luangtana-anan M (2007) Enhanced enteric properties and stability of shellac films through composite salts formation. Eur J Pharm Biopharm 67:690–698CrossRefGoogle Scholar
  22. Lowry O, Rosebrough N, Farr A, Randall R (1951) Protein measurement with the folin–phenol reagents. J Biol Chem 193:265–275Google Scholar
  23. Luangtana-anan M, Opanasopit P, Ngawhirunpat T, Nunthanid J, Sriamornsak P, Limmatvapirat S, Lim LY (2005) Effect of chitosan salts and molecular weight on a nanoparticulate carrier for therapeutic protein. Pharm Dev Technol 10:189–196CrossRefGoogle Scholar
  24. Luangtana-anan M, Limmatvapirat S, Nunthanid J, Chalongsuk R, Yamamoto K (2010) Polyethylene glycol on stability of chitosan microparticulate carrier for protein. AAPS PharmSciTech 11:1376–1382CrossRefGoogle Scholar
  25. Ma Z, Yeoh HH, Lim LY (2002) Formulation pH modulates the interaction of insulin nanoparticles. J Pharm Sci 91:1396–1404CrossRefGoogle Scholar
  26. Mao HQ, Roy K, Troung-Le VL, Janes KA, Lin KY, Wang Y, August JT, Leong KW (2001) Chitosan–DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency. J Control Release 70:399–421CrossRefGoogle Scholar
  27. McClean S, Prosser E, Meehan E, O’Malley D, Clarke N, Ramtoola Z, Brayden D (1998) Binding and uptake of biodegradable poly-dl-lactide micro- and nanoparticles in intestinal epithelia. Eur J Pharm Sci 6:153–163CrossRefGoogle Scholar
  28. Pan Y, Li YJ, Zhao HY, Zheng JM, Xu H, Wei G, Hao JS, Cui FD (2002) Bioadhesive polysaccharide in protein delivery system: chitosan nanoparticles improve the intestinal absorption of insulin in vivo. Int J Pharm 249:139–147CrossRefGoogle Scholar
  29. Rampino A, Borgogna M, Blasi P, Bellich B, Cesàro A (2013) Chitosan nanoparticles: preparation, size evolution and stability. Int J Pharm 455(1):219–228CrossRefGoogle Scholar
  30. Sakuma S, Hayashi M, Akashi M (2001) Design of nanoparticles composed of graft copolymers for oral peptide delivery. Adv Drug Deliver Rev 47:21–37CrossRefGoogle Scholar
  31. Sarmento B, Ferreira D, Veiga F, Ribeiro A (2006) Characterization of insulin-loaded alginate nanoparticles produced by ionotropic pre-gelation through DSC and FTIR studies. Carbohydr Polym 66:1–7CrossRefGoogle Scholar
  32. Shu XZ, Zhu KJ (2002) Controlled drug release properties of ionically cross-linked chitosan beads: the influence of anion structure. Int J Pharm 233:217–225CrossRefGoogle Scholar
  33. Tsai ML, Chen RH, Ba SW, Chen WY (2010) The storage stability of chitosan/tripolyphosphate nanoparticles in a phosphate buffer. Carbohydr Polym 84(2):756–761CrossRefGoogle Scholar
  34. Vila A, Sanchez A, Janes K, Behrens I, Kissel T, Jato JLV, Alonso MJ (2004) Low molecular weight chitosan nanoparticles as new carriers for nasal vaccine delivery in mice. Eur J Pharm Biopharm 57:123–131CrossRefGoogle Scholar
  35. Xiong W, Zhang Q, Yin F, Yu S, Ye T, Pan W, Yang X (2016) Auricularia auricular polysaccharide-low molecular weight chitosan polyelectrolyte complex nanoparticles: preparation and characterization. Asian J Pharm Sci 11(3):439–448CrossRefGoogle Scholar
  36. Xu Y, Du Y (2003) Effect of molecular structure of chitosan on protein delivery properties of chitosan nanoparticles. Int J Pharm 250:215–226CrossRefGoogle Scholar
  37. Yuan XB, Li H, Yuan YB (2006) Preparation of cholesterolmodified chitosan self-aggregates for delivery of drugs to ocular surface. Carbohydr Polym 65:337–345CrossRefGoogle Scholar
  38. Zhang C, Ping Q, Zhang H, Shen J (2003) Synthesis and characterization of water-soluble O-succinyl-chitosan. Euro Polym J 39:1629–1634CrossRefGoogle Scholar

Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2017

Authors and Affiliations

  • Manee Luangtana-anan
    • 1
    • 2
  • Jurairat Nunthanid
    • 1
    • 2
  • Sontaya Limmatvapirat
    • 1
    • 2
  1. 1.Department of Pharmaceutical Technology, Faculty of PharmacySilpakorn UniversityNakhon PathomThailand
  2. 2.Pharmaceutical Biopolymer Group (PBiG), Faculty of PharmacySilpakorn UniversityNakhon PathomThailand

Personalised recommendations