Skip to main content
Log in

5-Fluorouracil encapsulated HA/PLGA composite microspheres for cancer therapy

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

5-Fluorouracil (5FU) was successfully entrapped within poly(lactide-co-glycolide) (PLGA) and hydroyapatite (HA) composite microspheres using the emulsification/solvent extraction technique. The effects of HA to PLGA ratio, solvent ratio as well as polymer inherent viscosity (IV) on encapsulation efficiency were investigated. The degradation and drug release rates of the microspheres were studied for 5 weeks in vitro in phosphate buffered solution of pH 7.4 at 37 °C. The drug release profile followed a biphasic pattern with a small initial burst followed by a zero-order release for up to 35 days. The initial burst release decreased with increasing HA content. The potential of HA in limiting the initial burst release makes the incorporation of HA into PLGA microspheres advantageous since it reduces the risk of drug overdose from high initial bursts. The linear sustained drug release profile over the course of 5 weeks makes these 5-FU-loaded HA/PLGA composite microparticles a promising delivery system for the controlled release of chemotherapy drugs in the treatment of cancer.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Kohn J, Abramson S, Langer R. Bioresorbable and bioerodible materials, Ratner BD, Hoffman AS, Schoen FJ, Lemons JE, editors. Biomaterials science, an introduction to materials in medicine. 2nd ed. Elsevier; 2004: p. 115–27.

  2. Jain RA. The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials. 2000;21:2475–90.

    Article  CAS  Google Scholar 

  3. Heya T, Mikura Y, Nagai A, et al. Controlled release of thyrotropin releasing hormone from microspheres: evaluation of release profiles and pharmacokinetics after subcutaneous administration. J Pharm Sci. 1994;83:798–801.

    Article  CAS  Google Scholar 

  4. Jeffery H, Davis SS, O’Hagan DT. The preparation and characterization of poly(lactide-co-glycoloide) microparticles. II. The entrapment of a model protein using a (water-in-oil)-in-water emulsion solvent evaporation technique. Pharm Res. 1993;10:362–8.

    Article  CAS  Google Scholar 

  5. Uchida T, Martin S, Foster TP, et al. Dose and load studies for subcutaneous and oral delivery of poly(lactide-co-glycolide) microspheres containing ovalbumin. Pharm Res. 1994;11:1009–15.

    Article  CAS  Google Scholar 

  6. Song CX, Labhasetwar V, Murphy H, et al. Formulation and characterization of biodegradable nanoparticles for intravascular local drug delivery. J Control Release. 1997;43:197–212.

    Article  Google Scholar 

  7. Chen L, Apte RN, Cohen S. Characterization of PLGA microspheres for the controlled delivery of IL-1 for tumor immunotherapy. J Control Release. 1997;43:261–72.

    Article  Google Scholar 

  8. Menei P, Daniel V, Montero-Menei C, Brouillard M, Pouplard-Barthelaix A, Benoit JP. Biodegradation and brain tissue reaction to poly(d,l-lactide-co-glycolide) microspheres. Biomaterials. 1993;14:470–8.

    Article  CAS  Google Scholar 

  9. Geze A, Venier-Julienne MC, Saulnier P, Varlet P, Daumas-Duport C, Devauchelle P, Benoit JP. Modulated release of IdUrd from poly(d, l-lactide-co-glycolide) microspheres by addition of poly(d, l-lactide) oligomers. J Control Release. 1998;58:311–22.

    Article  Google Scholar 

  10. Pean JM, Venier-Julienne MC, Boury F, Menei P, Denizot B, Benoit JP. NGF release from poly(d,l-lactide-co-glycolide) microspheres: effects of some formulation parameters on encapsulated NGF stability. J Control Release. 1998;56:175–87.

    Article  CAS  Google Scholar 

  11. Boisdron-Celle M, Menei P, Benoit JP. Preparation and characterization of 5-fluorouracil-loaded microparticles as biodegradable anticancer drug carriers. J Pharm Pharmacol. 1995;47:108–14.

    Article  CAS  Google Scholar 

  12. Menei P, Boisdron-Celle M, Croue A, Guy G, Benoit JP. Effect of stereotactic implantation of biodegradable 5-fluorouracil-loaded microspheres in healthy and C6 glioma-bearing rats. Neurosurgery. 1996;39:117–23.

    Article  CAS  Google Scholar 

  13. Faisant N, Akiki J, Siepmann F, Benoit JP, Siepmann J. Effects of the type of release medium on drug release from PLGA-based microparticles: experiment and theory. Int J Pharm. 2006;314:189–97.

    Article  CAS  Google Scholar 

  14. Freiberg S, Zhu X. Polymer microspheres for controlled drug release. Int J Pharm. 2004;282:1–18.

    Article  CAS  Google Scholar 

  15. Langenbach RJ, Dancenberg PV, Heidelberger C. Thymidylate synthetase: mechanism of inhibition of 5-fluorouracil-2-deoxyuridylate. Biochem Biophys Res Commun. 1972;48:1565–71.

    Article  CAS  Google Scholar 

  16. Yoshikawa R, Kusunoki M, Yanagi H, Noda M, Furuyama J, Yamamura T, Hashimoro-Tamaoki T. Dual antitumor effects of 5-fluorouracil on the cell cycle in colorectal carcinoma cells: a novel target mechanism concept for pharmacokinetic modulating chemotherapy. Cancer Res. 2001;61:1029–37.

    CAS  Google Scholar 

  17. Yu J, Zhang L, Hwang PM, Rago C, Kinzler KW, Vogelstein B. Identification and classification of p-53 regulated genes. Proc Natl Acad Sco USA. 1999;96:14517–22.

    Article  CAS  Google Scholar 

  18. Diasio RB, Harris BE. Clinical pharmacology of 5-fluorouracil. Clin Pharmacokinet. 1989;16:215–37.

    Article  CAS  Google Scholar 

  19. Kubo M, Kuwayama N, Hirashima Y, Takaku A, Ogawa T, Endo S. Hydroxyapatite ceramics as a particulate embolic material: report of the clinical experience. Am J Neuroradiol. 2003;24:1545–7.

    Google Scholar 

  20. Prakesh KH, Kumar R, Ooi CP, Cheang P, Khor KA. Apparent solubility of hydroxyapatite in aqueous medium and its influence on the morphology of nanocrystallites with precipitation temperature. Langmuir. 2006;22:11002–8.

    Article  Google Scholar 

  21. Siepmann J, Faisant N, Akki J, Richard J, Benoit JP. Effect of the size of biodegradable microparticles on drug release: experiment and theory. J Control Release. 2004;96:123–34.

    Article  CAS  Google Scholar 

  22. Siepmann J, Faisant N, Benoit JP. A new mathematical model quantifying drug release from bioerodible microparticles using Monte Carlo simulations. Pharm Res. 2002;19:1885–93.

    Article  CAS  Google Scholar 

  23. Chen X, Ooi CP. Hydrolytic degradation and drug release properties of ganciclovir-loaded biodegradable microspheres. Acta Biomaterialia. 2008;4:1046–56.

    Article  CAS  Google Scholar 

  24. Yang YY, Chia HH, Chung TS. Effect of preparation temperature on the characteristics and release profiles of PLGA microspheres containing protein fabricated by double-emulsion solvent extraction/evaporation method. J Control Release. 2000;69:81–96.

    Article  CAS  Google Scholar 

  25. Li H, Chang J. pH-compensation effect of bioactive inorganic fillers on the degradation of PLGA. Compos Sci Technol. 2005;65:2226–32.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chui Ping Ooi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lin, Y., Li, Y. & Ooi, C.P. 5-Fluorouracil encapsulated HA/PLGA composite microspheres for cancer therapy. J Mater Sci: Mater Med 23, 2453–2460 (2012). https://doi.org/10.1007/s10856-012-4723-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-012-4723-2

Keywords

Navigation