Skip to main content
SpringerLink
Log in

Preparation of gelatin/hyaluronic acid microspheres with different morphologies for drug delivery

  • Original Paper
  • Published:
Polymer Bulletin Aims and scope Submit manuscript

Abstract

Gelatin/hyaluronic acid (Gel/HA) microspheres were prepared by emulsion–coagulation method using glutaraldehyde as cross-linker. The influence of treatment methods, including removing water by different concentrations of acetone/water solution and freeze drying, on surface morphology was also investigated. The in vitro release behaviors of icariin from smooth Gel/HA microspheres were also studied. The results indicated that the smooth and wrinkled Gel/HA microspheres were obtained when treated by pure acetone/water solution (volume ratio of 3:1) and pure acetone, respectively. More wrinkled microcracks could be observed when the Gel/HA microspheres were washed by pure acetone for longer time. The microspheres with porous structure were prepared when the obtained smooth Gel/HA microspheres were treated by freeze-drying method at −45 °C. The size of Gel/HA microspheres increased with increasing immersion time in distilled water and showed deeper and bigger pores after freeze-drying process. The cumulative drug release of icariin from the microspheres decreased with increasing GA content. The results of icariin release kinetics from Gel/HA microspheres indicated Fickian diffusion.

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

Access this article

Log in via an institution

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
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Kawaguchi H (2000) Functional polymer microspheres. Prog Polym Sci 25:1171

    Article  CAS  Google Scholar 

  2. Freiberg S, Zhu XX (2004) Polymer microspheres for controlled drug release. Int J Pharm 282:1

    Article  CAS  Google Scholar 

  3. Allemann E, Gurny R, Doelker E (1993) Drug loaded nanoparticle preparation methods and drug targeting issues. Eur J Pharm Biopharm 39:173

    CAS  Google Scholar 

  4. Chen YS, Chang JY, Cheng CY, Tsai FJ, Yao CH, Liu BS (2005) An in vivo evaluation of a biodegradable genipin-cross-linked gelatin peripheral nerve guide conduit material. Biomaterials 26:3911

    Article  CAS  Google Scholar 

  5. Ponticiello MS, Schinagl RM, Kadiyala S, Barry FP (2000) Gelatin based resorbable sponge as a carrier matrix for human mesenchymal stem cells in cartilage regeneration therapy. J Biomed Mater Res 52:246

    Article  CAS  Google Scholar 

  6. Peng ZY, Li ZP, Shen YQ (2012) Influence of chemical cross-linking on properties of gelatin/chitosan microspheres. Polym Plast Technol 51:381–385

    Article  CAS  Google Scholar 

  7. Peng ZY, Li ZP, Shen YQ (2012) Preparation and in vitro characterization of gelatin microspheres containing 5-fluorouracil. J Macromol Sci B 51:1117–1124

    Article  CAS  Google Scholar 

  8. Ohta S, Nitta N, Takahashi M, Murata K, Tabata Y (2007) Degradable gelatin microspheres as an embolic agent: an experimental study in a rabbit renal model. Korean J Radiol 8:418

    Article  Google Scholar 

  9. Rokhade AP, Agnihotri SA, Patil SA, Mallikarjuna NN, Kulkarni PV, Aminabhavi TM (2006) Semi-interpenetrating polymer network microspheres of gelatin and sodium carboxymethyl cellulose for controlled release of ketorolac tromethamine. Carbohyd Polym 65:243

    Article  CAS  Google Scholar 

  10. Babu VR, Kanth VR, Mukund JM, Aminabhavi TM (2010) Novel methyl cellulose-grafted-acrylamide/gelatin microspheres for controlled release of nifedipine. J Appl Polym Sci 115:3542

    Article  CAS  Google Scholar 

  11. Kajjari PB, Manjeshwar LS, Aminabhavi TM (2011) Semi-interpenetrating polymer network hydrogel blend microspheres of gelatin and hydroxyethyl cellulose for controlled release of theophylline. Indust Eng Chem Res 50:7833

    Article  CAS  Google Scholar 

  12. Phadke KV, Manjeshwar LS, Aminabhavi TM (2014) Microspheres of gelatin and poly(ethylene glycol) coated with ethyl cellulose for controlled release of metronidazole. Indust Eng Chem Res 53:6575

    Article  CAS  Google Scholar 

  13. Maria AV, Marcello R, Alessandra M, Manuela G, Paolo G, Francesco R, Flavio F (2004) Microwave-treated gelatin microspheres as drug delivery system. J Control Release 96:67

    Article  Google Scholar 

  14. Burdick JA, Prestwich GD (2011) Hyaluronic acid hydrogels for biomedical applications. Adv Mater 23:H41

    Article  CAS  Google Scholar 

  15. Collins MN, Birkinshaw C (2008) Physical properties of crosslinked hyaluronic acid hydrogels. J Mater Sci Mater Med 19:3335

    Article  CAS  Google Scholar 

  16. Collins MN, Birkinshaw C (2008) Investigation of the swelling behaviour of crosslinked hyaluronic acid films and hydro-gels produced using homogeneous reactions. J Appl Polym Sci 109:923

    Article  CAS  Google Scholar 

  17. Kim J, Park Y, Tae G, Lee KB, Hwang SJ, Kim IS, Noh I, Sun K (2008) Synthesis and characterization of matrix metalloprotease sensitive-low molecular weight hyaluronic acid based hydrogels. J Mater Sci Mater Med 19:3311

    Article  CAS  Google Scholar 

  18. Zhou ZH, Chen JH, Peng C, Huang TL, Zhou H, Ou BL, Chen J, Liu QQ, He SL, Cao DF, Huang HH, Xiang LJ (2014) Fabrication and physical properties of gelatin/sodium alginate/hyaluronic acid composite wound dressing hydrogel. J Macromol Sci A 51:318

    Article  CAS  Google Scholar 

  19. Yamane S, Iwasaki N, Majima T, Funakoshi T, Masuko T, Harada K, Minami A, Monde K, Nishimura S (2005) Feasibility of chitosan-based hyaluronic acid hybrid biomaterial for a novel scaffold in cartilage tissue engineering. Biomaterials 26:611

    Article  CAS  Google Scholar 

  20. Zhou ZH, He SL, Huang TL, Liu LH, Liu QQ, Zhao YM, Ou BL, Zeng WN, Yang ZM, Cao DF (2013) Degradation behavior and biological properties of gelatin/hyaluronic acid composite scaffolds. Mater Res Innov 17:420

    Article  CAS  Google Scholar 

  21. Zhou ZH, Yang ZM, Huang TL, Liu LH, Liu QQ, Zhao YM, Zeng WN, Yi QF, Cao DF (2013) Effect of chemical cross-linking on properties of gelatin/hyaluronic acid composite hydrogels. Polym Plast Technol 52:45

    Article  CAS  Google Scholar 

  22. Muvaffak A, Hasirci N (2002) Controlled release from glutaraldehyde crosslinked gelatin microspheres. Technol Health Care 10:347

    Google Scholar 

  23. Sun XD, Sun XW, Jin XD, Zhang XL, Liu CL, Lei L, Jin LH, Liu HW (2011) Icariin induces mouse embryonic stem cell differentiation into beating functional cardiomyocytes. Mol Cell Biochem 349:117

    Article  CAS  Google Scholar 

  24. Su M, Na Li, Tian JZ (2012) Preparation technology of total combined with icariin saponins from panax notoginseng chitosan microspheres. Chin J Exp Tradit Med Formul 18:30

    CAS  Google Scholar 

  25. Zhang AH, Yao KD (2006) Preparation and in vitro release of icariin-loaded chitosan/gelatin microsphere. Polym Bull 4:60

    Google Scholar 

  26. Molin SO, Nygren H, Dolonius L (1978) A new method for the study of glutaraldehyde-induced crosslinking properties in proteins with special reference to the reaction with amino groups. J Histochem Cytochem 26:412

    Article  CAS  Google Scholar 

  27. Zhou ZH, Liu LH, Liu QQ, Zhao YM, Xu GR, Tang AP, Zeng WN, Zhou JN (2012) Study on controlled release of 5-fluorouracil from gelatin/chitosan microspheres. J Macromol Sci A 49:1030

    Article  CAS  Google Scholar 

  28. Peppas NA (1985) Analysis of Fickian and non-Fickian drug release from polymers. Pharm Acta Helv 60:110

    CAS  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the National Natural Science Fund of China (No. 51273062 and No. 51443002), the Hunan Provincial Natural Science Fund of China (No. 12JJA003) and the Aid Program for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province.

Author information

Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan, People’s Republic of China

    Zhihua Zhou, Siliang He, Hu Zhou, Qingquan Liu, Wennan Zeng, Lihua Liu, Huihua Huang, Liujiao Xiang & Hua Yan

  2. Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan University of Science and Technology, Xiangtan, People’s Republic of China

    Zhihua Zhou

  3. Hunan Province College Key Laboratory of QSAR/QSPR, Hunan University of Science and Technology, Xiangtan, People’s Republic of China

    Zhihua Zhou

  4. Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China

    Tianlong Huang

  5. Department of Burns and Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China

    Cheng Peng

Authors
  1. Zhihua Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Siliang He
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tianlong Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cheng Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hu Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qingquan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wennan Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lihua Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Huihua Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Liujiao Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hua Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhihua Zhou.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, Z., He, S., Huang, T. et al. Preparation of gelatin/hyaluronic acid microspheres with different morphologies for drug delivery. Polym. Bull. 72, 713–723 (2015). https://doi.org/10.1007/s00289-015-1300-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00289-015-1300-0

Keywords

Search

Navigation