Skip to main content
Log in

A modified spontaneous emulsification solvent diffusion method for the preparation of curcumin-loaded PLGA nanoparticles with enhanced in vitro anti-tumor activity

  • Research Article
  • Published:
Frontiers of Materials Science Aims and scope Submit manuscript

Abstract

To improve the anti-tumor activity of hydrophobic drug curcumin, we prepared curcumin-loaded PLGA nanoparticles (PLGA-Cur NPs) through a modified spontaneous emulsification solvent diffusion (modified-SESD) method. The influence of main preparation parameters was investigated, such as the volume ratio of binary organic solvents and the concentration of surfactant. Results indicated that the synthesized regular spherical PLGA NPs with the average diameter of 189.7 nm exhibited relatively higher yield (58.9%), drug loading (11.0% (w/w)) and encapsulation efficiency (33.5%), and also a controllable drug release profile. In order to evaluate the in vitro cytotoxicity of the prepared NPs, MTT assay was conducted, and results showed that the NPs could effectively inhibit HL60 and HepG2 cells with lower IC50 values compared with free curcumin. Furthermore, confocal microscopy together with flow cytometry analysis proved the enhanced apoptosis-inducing ability of PLGA-Cur NPs. Polymeric NP formulations are potential to be used for hydrophobic drug delivery systems in cancer therapy.

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.

Similar content being viewed by others

References

  1. Heeba G H, Mahmoud M E, Hanafy A A. Anti-inflammatory potential of curcumin and quercetin in rats: Role of oxidative stress, heme oxygenase-1 and TNF-α. Toxicology and Industrial Health, 2012, 30(6): 551–560

    Article  Google Scholar 

  2. Bhullar K S, Jha A, Youssef D, et al. Curcumin and its carbocyclic analogs: structure-activity in relation to antioxidant and selected biological properties. Molecules, 2013, 18(5): 5389–5404

    Article  Google Scholar 

  3. Zemljic L F, Volmajer J, Ristic T, et al. Antimicrobial and antioxidant functionalization of viscose fabric using chitosan-curcumin formulations. Textile Research Journal, 2014, 84(8): 819–830

    Article  Google Scholar 

  4. Gong C, Deng S, Wu Q, et al. Improving antiangiogenesis and anti-tumor activity of curcumin by biodegradable polymeric micelles. Biomaterials, 2013, 34(4): 1413–1432

    Article  Google Scholar 

  5. Fan X, Zhang C, Liu D B, et al. The clinical applications of curcumin: current state and the future. Current Pharmaceutical Design, 2013, 19(11): 2011–2031

    Google Scholar 

  6. Liu H, Liu Y Z, Zhang F, et al. Identification of potential pathways involved in the induction of cell cycle arrest and apoptosis by a new 4-arylidene curcumin analogue T63 in lung cancer cells: a comparative proteomic analysis. Molecular BioSystems, 2014, 10(6): 1320–1331

    Article  Google Scholar 

  7. Verderio P, Bonetti P, Colombo M, et al. Intracellular drug release from curcumin-loaded PLGA nanoparticles induces G2/M block in breast cancer cells. Biomacromolecules, 2013, 14(3): 672–682

    Article  Google Scholar 

  8. Ono M, Higuchi T, Takeshima M, et al. Differential anti-tumor activities of curcumin against Ras- and Src-activated human adenocarcinoma cells. Biochemical and Biophysical Research Communications, 2013, 436(2): 186–191

    Article  Google Scholar 

  9. Chang Z, Xing J, Yu X. Curcumin induces osteosarcoma MG63 cells apoptosis via ROS/Cyto-C/Caspase-3 pathway. Tumour Biology, 2014, 35(1): 753–758

    Article  Google Scholar 

  10. Li B, Konecke S, Wegiel L A, et al. Both solubility and chemical stability of curcumin are enhanced by solid dispersion in cellulose derivative matrices. Carbohydrate Polymers, 2013, 98(1): 1108–1116

    Article  Google Scholar 

  11. Rachmawati H, Al Shaal L, Müller R H, et al. Development of curcumin nanocrystal: physical aspects. Journal of Pharmaceutical Sciences, 2013, 102(1): 204–214

    Article  Google Scholar 

  12. Barui S, Saha S, Mondal G, et al. Simultaneous delivery of doxorubicin and curcumin encapsulated in liposomes of pegylated RGDK-lipopeptide to tumor vasculature. Biomaterials, 2014, 35(5): 1643–1656

    Article  Google Scholar 

  13. Zhao R B, Yang X Y, Chen C, et al. The anti-tumour effect of p53 gene loaded hydroxyapatite nanoparticles in vitro and in vivo. Journal of Nanoparticle Research, 2014, 16(4): 2353–2367

    Article  Google Scholar 

  14. Chuah L H, Roberts C J, Billa N, et al. Cellular uptake and anticancer effects of mucoadhesive curcumin-containing chitosan nanoparticles. Colloids and Surfaces B: Biointerfaces, 2014, 116: 228–236

    Article  Google Scholar 

  15. Nakayama M, Akimoto J, Okano T. Polymeric micelles with stimuli-triggering systems for advanced cancer drug targeting. Journal of Drug Targeting, 2014, 22(7): 584–599

    Article  Google Scholar 

  16. Ma J, Yang F, Both S K, et al. Comparison of cell-loading methods in hydrogel systems. Journal of Biomedical Materials Research Part A, 2014, 102(4): 935–946

    Article  Google Scholar 

  17. Ravichandran R. Studies on dissolution behaviour of nanoparticulate curcumin formulation. Advances in Nanoparticles, 2013, 2(1): 51–59

    Article  Google Scholar 

  18. Ye F, Barrefelt A, Asem H, et al. Biodegradable polymeric vesicles containing magnetic nanoparticles, quantum dots and anticancer drugs for drug delivery and imaging. Biomaterials, 2014, 35(12): 3885–3894

    Article  Google Scholar 

  19. Guerrero-Cázares H, Tzeng S Y, Young N P, et al. Biodegradable polymeric nanoparticles show high efficacy and specificity at DNA delivery to human glioblastoma in vitro and in vivo. ACS Nano, 2014, 8(5): 5141–5153

    Article  Google Scholar 

  20. Danhier F, Ansorena E, Silva J M, et al. PLGA-based nanoparticles: an overview of biomedical applications. Journal of Controlled Release, 2012, 161(2): 505–522

    Article  Google Scholar 

  21. Cui Y, Xu Q, Chow P K H, et al. Transferrin-conjugated magnetic silica PLGA nanoparticles loaded with doxorubicin and paclitaxel for brain glioma treatment. Biomaterials, 2013, 34(33): 8511–8520

    Article  Google Scholar 

  22. Paul A, Das S, Das J, et al. Cytotoxicity and apoptotic signalling cascade induced by chelidonine-loaded PLGA nanoparticles in HepG2 cells in vitro and bioavailability of nano-chelidonine in mice in vivo. Toxicology Letters, 2013, 222(1): 10–22

    Article  Google Scholar 

  23. Yang Z, Luo X, Zhang X, et al. Targeted delivery of 10-hydroxycamptothecin to human breast cancers by cyclic RGDmodified lipid-polymer hybrid nanoparticles. Biomedical Materials, 2013, 8(2): 025012

    Article  Google Scholar 

  24. Xiong S, Zhao X, Heng B C, et al. Cellular uptake of Poly-(D,Llactide-co-glycolide) (PLGA) nanoparticles synthesized through solvent emulsion evaporation and nanoprecipitation method. Biotechnology Journal, 2011, 6(5): 501–508

    Article  Google Scholar 

  25. Xu A, Yao M, Xu G, et al. A physical model for the size-dependent cellular uptake of nanoparticles modified with cationic surfactants. International Journal of Nanomedicine, 2012, 7: 3547–3554

    Google Scholar 

  26. Ye Z, Squillante E. The development and scale-up of biodegradable polymeric nanoparticles loaded with ibuprofen. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2013, 422(5): 75–80

    Article  Google Scholar 

  27. Murakami H, Kobayashi M, Takeuchi H, et al. Further application of a modified spontaneous emulsification solvent diffusion method to various types of PLGA and PLA polymers for preparation of nanoparticles. Powder Technology, 2000, 107(1–2): 137–143

    Article  Google Scholar 

  28. Fadok V A, Bratton D L, Frasch S C, et al. The role of phosphatidylserine in recognition of apoptotic cells by phagocytes. Cell Death and Differentiation, 1998, 5(7): 551–562

    Article  Google Scholar 

  29. Wang H, Tang X, Tang G, et al. Noninvasive positron emission tomography imaging of cell death using a novel small-molecule probe, (18)F labeled bis(zinc(II)-dipicolylamine) complex. Apoptosis, 2013, 18(8): 1017–1027

    Article  Google Scholar 

  30. Darzynkiewicz Z, Bruno S, Del Bino G, et al. Features of apoptotic cells measured by flow cytometry. Cytometry, 1992, 13(8): 795–808

    Article  Google Scholar 

  31. Kamat AM, Tharakan S T, Sung B, et al. Curcumin potentiates the antitumor effects of Bacillus Calmette-Guerin against bladder cancer through the downregulation of NF-κB and upregulation of TRAIL receptors. Cancer Research, 2009, 69(23): 8958–8966

    Article  Google Scholar 

  32. Callewaert M, Dukic S, Van Gulick L, et al. Etoposide encapsulation in surface-modified poly(lactide-co-glycolide) nanoparticles strongly enhances glioma antitumor efficiency. Journal of Biomedical Materials Research Part A, 2013, 101A(5): 1319–1327

    Article  Google Scholar 

  33. Ibrahim M M, Abd-Elgawad A E H, Soliman O A E, et al. Nanoparticle-based topical ophthalmic formulations for sustained celecoxib release. Journal of Pharmaceutical Sciences, 2013, 102(3): 1036–1053

    Article  Google Scholar 

  34. Li G, Lin D H, Xie X X, et al. Uptake and transport of furanodiene in Caco-2 cell monolayers: a comparison study between furanodiene and furanodiene loaded PLGA nanoparticles. Chinese Journal of Natural Medicine, 2013, 11(1): 49–55

    Article  Google Scholar 

  35. Zhang Y, Chan H F, Leong K W. Advanced materials and processing for drug delivery: the past and the future. Advanced Drug Delivery Reviews, 2013, 65(1): 104–120

    Article  Google Scholar 

  36. Kumar S S D, Surianarayanan M, Vijayaraghavan R, et al. Curcumin loaded poly(2-hydroxyethyl methacrylate) nanoparticles from gelled ionic liquid — in vitro cytotoxicity and anticancer activity in SKOV-3 cells. European Journal of Pharmaceutical Sciences, 2014, 51: 34–44

    Article  Google Scholar 

  37. Henry C M, Hollville E, Martin S J. Measuring apoptosis by microscopy and flow cytometry. Methods, 2013, 61(2): 90–97

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xiang-Dong Kong.

Additional information

C.C and W.Y. contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, C., Yang, W., Wang, DT. et al. A modified spontaneous emulsification solvent diffusion method for the preparation of curcumin-loaded PLGA nanoparticles with enhanced in vitro anti-tumor activity. Front. Mater. Sci. 8, 332–342 (2014). https://doi.org/10.1007/s11706-014-0268-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11706-014-0268-2

Keywords

Navigation