Skip to main content

Advertisement

SpringerLink
Log in

Magnetite/poly(D,L-lactide-co-glycolide) and hydroxyapatite/poly(D,L-lactide-co-glycolide) prepared by w/o/w emulsion technique for drug carrier: physical characteristic of composite nanoparticles

  • Original Contribution
  • Published:
Colloid and Polymer Science Aims and scope Submit manuscript

Abstract

Poly(D,L-lactide-co-glycolide) (PLGA) with encapsulated hydrophobic magnetite (Fe3O4) nanoparticles or hydroxyapatite (HAp) nanoparticles were prepared by the w/o/w emulsion technique. The weight ratios of nanoparticles (Fe3O4 or HAp) to PLGA and polymer molecular weight were varied in the oil phase and the properties of the composite nanoparticles were studied. The final weight percent of nanoparticles in the spherical PLGA particles varied from ~ 5 to 60 wt%. Hydrodynamic diameters of the composite nanoparticles as measured by dynamic light scattering (DLS) were found to decrease with decreasing polymer molecular weight and were independent of nanoparticle loading. Particle sizes measured from TEM were smaller by almost a factor of two vs. those obtained from DLS. The zeta potentials of the particles were about − 23 mV, independent of polymer molecular weight and nanoparticle loading within statistical significance. In vitro cytotoxicity tests show a high level of cytocompatibility suggesting satisfactory biocompatibility for biomedical applications.

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. Ito A, Kamihira M (2011) Chapter 9 - Tissue engineering using magnetite nanoparticles. Progress in molecular biology and translational science, vol 104. Academic Press, pp 355–395. https://doi.org/10.1016/B978-0-12-416020-0.00009-7

  2. Aguilar ZP (2013) Chapter 5 - Targeted drug delivery. Nanomaterials for medical applications. Elsevier, pp 181–234. https://doi.org/10.1016/B978-0-12-385089-8.00005-4

  3. Torres FG, Nazhat SN, Sheikh Md Fadzullah SH, Maquet V, Boccaccini AR (2007) Mechanical properties and bioactivity of porous PLGA/TiO2 nanoparticle-filled composites for tissue engineering scaffolds. Compos Sci Technol 67(6):1139–1147. https://doi.org/10.1016/j.compscitech.2006.05.018

    Article  CAS  Google Scholar 

  4. Kim J-H, Sheikh FA, Ju HW, Park HJ, Moon BM, Lee OJ, Park CH (2014) 3D silk fibroin scaffold incorporating titanium dioxide (TiO2) nanoparticle (NPs) for tissue engineering. Int J Biol Macromol 68:158–168. https://doi.org/10.1016/j.ijbiomac.2014.04.045

    Article  CAS  Google Scholar 

  5. Leung KC-F, Lee S-F, Wong C-H, Chak C-P, Lai JMY, Zhu X-M, Wang Y-XJ, Sham KWY, Cheng CHK (2013) Nanoparticle–DNA–polymer composites for hepatocellular carcinoma cell labeling, sensing, and magnetic resonance imaging. Methods 64(3):315–321. https://doi.org/10.1016/j.ymeth.2013.06.006

    Article  CAS  Google Scholar 

  6. Liu Z, Lammers T, Ehling J, Fokong S, Bornemann J, Kiessling F, Gätjens J (2011) Iron oxide nanoparticle-containing microbubble composites as contrast agents for MR and ultrasound dual-modality imaging. Biomaterials 32(26):6155–6163. https://doi.org/10.1016/j.biomaterials.2011.05.019

    Article  CAS  Google Scholar 

  7. Khandhar AP, Ferguson RM, Arami H, Krishnan KM (2013) Monodisperse magnetite nanoparticle tracers for in vivo magnetic particle imaging. Biomaterials 34(15):3837–3845. https://doi.org/10.1016/j.biomaterials.2013.01.087

    Article  CAS  Google Scholar 

  8. Probst CE, Zrazhevskiy P, Bagalkot V, Gao X (2013) Quantum dots as a platform for nanoparticle drug delivery vehicle design. Adv Drug Deliv Rev 65(5):703–718. https://doi.org/10.1016/j.addr.2012.09.036

    Article  CAS  Google Scholar 

  9. Wen H, Guo J, Chang B, Yang W (2013) pH-responsive composite microspheres based on magnetic mesoporous silica nanoparticle for drug delivery. Eur J Pharm Biopharm 84(1):91–98. https://doi.org/10.1016/j.ejpb.2012.11.019

    Article  CAS  Google Scholar 

  10. Kanapathipillai M, Brock A, Ingber DE Nanoparticle targeting of anti-cancer drugs that alter intracellular signaling or influence the tumor microenvironment. Adv Drug Deliv Rev. https://doi.org/10.1016/j.addr.2014.05.005

  11. Li Q, Zhou Y, Ma K, Wei Q, Nie Z (2016) A mesoporous SiO2/dense SiO2/Fe3O4 multiply coated hollow microsphere: synthesis and application on papain immobilization. Colloids Surf A Physicochem Eng Asp 511:239–246. https://doi.org/10.1016/j.colsurfa.2016.08.088

    Article  CAS  Google Scholar 

  12. William WY, Emmanuel C, Christie MS, Rebekah D, Vicki LC (2006) Aqueous dispersion of monodisperse magnetic iron oxide nanocrystals through phase transfer. Nanotechnology 17(17):4483

    Article  Google Scholar 

  13. Yuan Q, Venkatasubramanian R, Hein S, Misra RDK (2008) A stimulus-responsive magnetic nanoparticle drug carrier: magnetite encapsulated by chitosan-grafted-copolymer. Acta Biomater 4(4):1024–1037. https://doi.org/10.1016/j.actbio.2008.02.002

    Article  CAS  Google Scholar 

  14. Fernandes-Cunha GM, Rezende CM, Mussel WN, da Silva GR, Elionai CDL, Yoshida MI, Fialho SL, Goes AM, Gomes DA, de Almeida Vitor RW, Silva-Cunha A (2016) Anti-toxoplasma activity and impact evaluation of lyophilization, hot molding process, and gamma-irradiation techniques on CLH-PLGA intravitreal implants. J Mater Sci Mater Med 27(1):10. https://doi.org/10.1007/s10856-015-5621-1

  15. Blum JS, Saltzman WM (2008) High loading efficiency and tunable release of plasmid DNA encapsulated in submicron particles fabricated from PLGA conjugated with poly-L-lysine. J Control Release 129(1):66–72. https://doi.org/10.1016/j.jconrel.2008.04.002

    Article  CAS  Google Scholar 

  16. Khang G, Rhee J, Jeong J, Lee J, Kim M, Cho S, Lee H (2003) Local drug delivery system using biodegradable polymers. Macromol Res 11(4):207–223. https://doi.org/10.1007/BF03218355

    Article  CAS  Google Scholar 

  17. Kimura H, Ogura Y (2001) Biodegradable polymers for ocular drug delivery. Ophthalmologica 215(3):143–155

    Article  CAS  Google Scholar 

  18. Chertok B, David AE, Yang VC (2011) Brain tumor targeting of magnetic nanoparticles for potential drug delivery: effect of administration route and magnetic field topography. J Control Release 155(3):393–399. https://doi.org/10.1016/j.jconrel.2011.06.033

    Article  CAS  Google Scholar 

  19. Kempe H, Kempe M (2010) The use of magnetite nanoparticles for implant-assisted magnetic drug targeting in thrombolytic therapy. Biomaterials 31(36):9499–9510. https://doi.org/10.1016/j.biomaterials.2010.07.107

    Article  CAS  Google Scholar 

  20. Iglesias G, Delgado AV, Kujda M, Ramos-Tejada MM (2016) Magnetic hyperthermia with magnetite nanoparticles: electrostatic and polymeric stabilization. Colloid Polym Sci 294(10):1541–1550. https://doi.org/10.1007/s00396-016-3918-3

    Article  CAS  Google Scholar 

  21. Wei Y, Yin G, Ma C, Huang Z, Chen X, Liao X, Yao Y, Yin H (2013) Synthesis and cellular compatibility of biomineralized Fe3O4 nanoparticles in tumor cells targeting peptides. Colloids Surf B: Biointerfaces 107:180–188. https://doi.org/10.1016/j.colsurfb.2013.01.058

    Article  CAS  Google Scholar 

  22. Yang J, Park SB, Yoon H-G, Huh YM, Haam S (2006) Preparation of poly ɛ-caprolactone nanoparticles containing magnetite for magnetic drug carrier. Int J Pharm 324(2):185–190. https://doi.org/10.1016/j.ijpharm.2006.06.029

    Article  CAS  Google Scholar 

  23. Bourne D, Grady B, Chen K, Dormer K, Kopke RD, Wang Y, Gao X, Kuriyavar S (2011) Incorporation, release, and effectiveness of dexamethasone in poly(lactic-co-glycolic acid) nanoparticles for inner ear drug delivery. J Nanotechnol Eng Med 2(1):011013–011013. https://doi.org/10.1115/1.4002928

    Article  Google Scholar 

  24. Rajan B, Sathish S, Jayakumar S, Madankumar A, Gokuladhas K, Premkumar T, Elamaran R, Gopikrishnan M, Devaki T Synthesis and in vitro anticancer evaluation of 2-isopropyl-5-methylphenol loaded PLGA based iron oxide nanoparticles. Biomed Prev Nutr. https://doi.org/10.1016/j.bionut.2013.12.004

  25. Kilpadi KL, Chang PL, Bellis SL (2001) Hydroxylapatite binds more serum proteins, purified integrins, and osteoblast precursor cells than titanium or steel. J Biomed Mater Res 57(2):258–267

    Article  CAS  Google Scholar 

  26. Tahmasebi Birgani Z, van Blitterswijk CA, Habibovic P (2016) Monolithic calcium phosphate/poly(lactic acid) composite versus calcium phosphate-coated poly(lactic acid) for support of osteogenic differentiation of human mesenchymal stromal cells. J Mater Sci Mater Med 27(3):54. https://doi.org/10.1007/s10856-016-5666-9

    Article  Google Scholar 

  27. Kenny SM, Buggy M (2003) Bone cements and fillers: a review. J Mater Sci Mater Med 14(11):923–938. https://doi.org/10.1023/A:1026394530192

    Article  CAS  Google Scholar 

  28. Pines A, Raafat H, Lynn AH, Whittington J (1984) Clinical trial of microcrystalline hydroxyapatite compound (‘Ossopan’) in the prevention of osteoporosis due to corticosteroid therapy. Curr Med Res Opin 8(10):734–742. https://doi.org/10.1185/03007998409110124

    Article  CAS  Google Scholar 

  29. Rüegsegger P, Keller A, Dambacher MA (1995) Comparison of the treatment effects of ossein-hydroxyapatite compound and calcium carbonate in osteoporotic females. Osteoporos Int 5(1):30–34. https://doi.org/10.1007/BF01623655

    Article  Google Scholar 

  30. Matsumoto T, Okazaki M, Inoue M, Yamaguchi S, Kusunose T, Toyonaga T, Hamada Y, Takahashi J (2004) Hydroxyapatite particles as a controlled release carrier of protein. Biomaterials 25(17):3807–3812. https://doi.org/10.1016/j.biomaterials.2003.10.081

    Article  CAS  Google Scholar 

  31. Stigter M, Bezemer J, de Groot K, Layrolle P (2004) Incorporation of different antibiotics into carbonated hydroxyapatite coatings on titanium implants, release and antibiotic efficacy. J Control Release 99(1):127–137. https://doi.org/10.1016/j.jconrel.2004.06.011

    Article  CAS  Google Scholar 

  32. Xu Q, Tanaka Y, Czernuszka JT (2007) Encapsulation and release of a hydrophobic drug from hydroxyapatite coated liposomes. Biomaterials 28(16):2687–2694. https://doi.org/10.1016/j.biomaterials.2007.02.007

    Article  CAS  Google Scholar 

  33. Hamoudeh M, Faraj AA, Canet-Soulas E, Bessueille F, Léonard D, Fessi H (2007) Elaboration of PLLA-based superparamagnetic nanoparticles: characterization, magnetic behaviour study and in vitro relaxivity evaluation. Int J Pharm 338(1–2):248–257. https://doi.org/10.1016/j.ijpharm.2007.01.023

    Article  CAS  Google Scholar 

  34. Jain RA (2000) The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials 21(23):2475–2490. https://doi.org/10.1016/S0142-9612(00)00115-0

    Article  CAS  Google Scholar 

  35. Jensen DK, Jensen LB, Koocheki S, Bengtson L, Cun D, Nielsen HM, Foged C (2012) Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA. J Control Release 157(1):141–148. https://doi.org/10.1016/j.jconrel.2011.08.011

    Article  CAS  Google Scholar 

  36. Zhang H, Cui W, Bei J, Wang S (2006) Preparation of poly(lactide-co-glycolide-co-caprolactone) nanoparticles and their degradation behaviour in aqueous solution. Polym Degrad Stab 91(9):1929–1936. https://doi.org/10.1016/j.polymdegradstab.2006.03.004

    Article  CAS  Google Scholar 

  37. Okassa LN, Marchais H, Douziech-Eyrolles L, Hervé K, Cohen-Jonathan S, Munnier E, Soucé M, Linassier C, Dubois P, Chourpa I (2007) Optimization of iron oxide nanoparticles encapsulation within poly(d,l-lactide-co-glycolide) sub-micron particles. Eur J Pharm Biopharm 67(1):31–38. https://doi.org/10.1016/j.ejpb.2006.12.020

    Article  CAS  Google Scholar 

  38. Zheng W, Gao F, Gu H (2005) Magnetic polymer nanospheres with high and uniform magnetite content. J Magn Magn Mater 288:403–410. https://doi.org/10.1016/j.jmmm.2004.09.125

    Article  CAS  Google Scholar 

  39. Makadia HK, Siegel SJ (2011) Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers 3(3):1377–1397. https://doi.org/10.3390/polym3031377

    Article  CAS  Google Scholar 

  40. Caldorera-Moore M, Guimard N, Shi L, Roy K (2010) Designer nanoparticles: incorporating size, shape, and triggered release into nanoscale drug carriers. Expert Opin Drug Deliv 7(4):479–495. https://doi.org/10.1517/17425240903579971

    Article  CAS  Google Scholar 

  41. Panyam J, Dali MM, Sahoo SK, Ma W, Chakravarthi SS, Amidon GL, Levy RJ, Labhasetwar V (2003) Polymer degradation and in vitro release of a model protein from poly(d,l-lactide-co-glycolide) nano- and microparticles. J Control Release 92(1–2):173–187. https://doi.org/10.1016/S0168-3659(03)00328-6

    Article  CAS  Google Scholar 

  42. Patil VRS, Campbell CJ, Yun YH, Slack SM, Goetz DJ (2001) Particle diameter influences adhesion under flow. Biophys J 80(4):1733–1743. https://doi.org/10.1016/S0006-3495(01)76144-9

    Article  Google Scholar 

  43. Ilium L, Davis SS, Wilson CG, Thomas NW, Frier M, Hardy JG (1982) Blood clearance and organ deposition of intravenously administered colloidal particles. The effects of particle size, nature and shape. Int J Pharm 12(2):135–146. https://doi.org/10.1016/0378-5173(82)90113-2

    Article  Google Scholar 

  44. Tabata Y, Ikada Y (1990) Phagocytosis of polymer microspheres by macrophages. New polymer materials. Springer Berlin Heidelberg, Berlin, Heidelberg, pp 107–141. https://doi.org/10.1007/BFb0043062

  45. Rejman J, Oberle V, Zuhorn IS, Hoekstra D (2004) Size-dependent internalization of particles via the pathways of clathrin-and caveolae-mediated endocytosis. Biochem J 377(1):159–169. https://doi.org/10.1042/BJ20031253

    Article  CAS  Google Scholar 

  46. Kim B, Han G, Toley BJ, Kim CK, Rotello VM, Forbes NS (2010) Tuning payload delivery in tumour cylindroids using gold nanoparticles. Nat Nanotechnol 5(6):465–472. https://doi.org/10.1038/nnano.2010.58

    Article  CAS  Google Scholar 

  47. Bootdee K, Nithitanakul M, Grady B (2012) Synthesis and encapsulation of magnetite nanoparticles in PLGA: effect of amount of PLGA on characteristics of encapsulated nanoparticles. Polym Bull 69(7):795–806. https://doi.org/10.1007/s00289-012-0773-3

    Article  CAS  Google Scholar 

  48. Wassel RA, Grady B, Kopke RD, Dormer KJ (2007) Dispersion of super paramagnetic iron oxide nanoparticles in poly(d,l-lactide-co-glycolide) microparticles. Colloids Surf A Physicochem Eng Asp 292(2–3):125–130. https://doi.org/10.1016/j.colsurfa.2006.06.012

    Article  CAS  Google Scholar 

  49. Zhang L, He R, Gu H-C (2006) Oleic acid coating on the monodisperse magnetite nanoparticles. Appl Surf Sci 253(5):2611–2617. https://doi.org/10.1016/j.apsusc.2006.05.023

    Article  CAS  Google Scholar 

  50. Zhao Y, Qiu Z, Huang J (2008) Preparation and analysis of Fe3O4 magnetic nanoparticles used as targeted-drug carriers. Chin J Chem Eng 16(3):451–455. https://doi.org/10.1016/S1004-9541(08)60104-4

    Article  CAS  Google Scholar 

  51. Wei Y, Han B, Hu X, Lin Y, Wang X, Deng X (2012) Synthesis of Fe3O4 nanoparticles and their magnetic properties. Procedia Eng 27:632–637. https://doi.org/10.1016/j.proeng.2011.12.498

    Article  CAS  Google Scholar 

  52. Liu X, Kaminski MD, Guan Y, Chen H, Liu H, Rosengart AJ (2006) Preparation and characterization of hydrophobic superparamagnetic magnetite gel. J Magn Magn Mater 306(2):248–253. https://doi.org/10.1016/j.jmmm.2006.03.049

    Article  CAS  Google Scholar 

  53. Astete CE, Kumar CSSR, Sabliov CM (2007) Size control of poly(d,l-lactide-co-glycolide) and poly(d,l-lactide-co-glycolide)-magnetite nanoparticles synthesized by emulsion evaporation technique. Colloids Surf A Physicochem Eng Asp 299(1–3):209–216. https://doi.org/10.1016/j.colsurfa.2006.11.055

    Article  CAS  Google Scholar 

  54. Harris LA, Goff JD, Carmichael AY, Riffle JS, Harburn JJ, St Pierre TG, Saunders M (2003) Magnetite nanoparticle dispersions stabilized with triblock copolymers. Chem Mater 15(6):1367–1377

    Article  CAS  Google Scholar 

  55. Scheers EM, Ekwall B, Dierickx PJ (2001) In vitro long-term cytotoxicity testing of 27 MEIC chemicals on Hep G2 cells and comparison with acute human toxicity data. Toxicol In Vitro 15(2):153–161

    Article  CAS  Google Scholar 

  56. Dierickx P (2005) Prediction of human acute toxicity by the hep G2/24-hour/total protein assay, with protein measurement by the CBQCA method. Altern Lab Anim: ATLA 33(3):207–213

    CAS  Google Scholar 

  57. Verma NK, Crosbie-Staunton K, Satti A, Gallagher S, Ryan KB, Doody T, McAtamney C, MacLoughlin R, Galvin P, Burke CS, Volkov Y, Gun'ko YK (2013) Magnetic core-shell nanoparticles for drug delivery by nebulization. J Nanobiotechnol 11:1. https://doi.org/10.1186/1477-3155-11-1

    Article  CAS  Google Scholar 

  58. Dutra Messias A, Aragones A, Eliana ARD (2009) PLGA-hydroxyapatite composite scaffolds for osteoblastic-like cells. Key Eng Mater 396–398:461–464. https://doi.org/10.4028/www.scientific.net/KEM.396-398.461

Download references

Acknowledgements

We are grateful for the funding from Government Research Budget, Chulalongkorn University.

Funding

This work was supported by the Government Research Budget, Chulalongkorn University.

Author information

Authors and Affiliations

  1. The Petroleum and Petrochemical College, Chulalongkorn University, Bangkok, 10330, Thailand

    Kittima Bootdee & Manit Nithitanakul

  2. University of Oklahoma School of Chemical, Biological and Materials Engineering, Norman, OK, 73019, USA

    Brian P. Grady

Authors
  1. Kittima Bootdee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian P. Grady
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Manit Nithitanakul
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Manit Nithitanakul.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bootdee, K., Grady, B.P. & Nithitanakul, M. Magnetite/poly(D,L-lactide-co-glycolide) and hydroxyapatite/poly(D,L-lactide-co-glycolide) prepared by w/o/w emulsion technique for drug carrier: physical characteristic of composite nanoparticles. Colloid Polym Sci 295, 2031–2040 (2017). https://doi.org/10.1007/s00396-017-4185-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00396-017-4185-7

Keywords

Search

Navigation