10.1007/s40204-014-0033-8

Development of microspheres for biomedical applications: a review

HTML PDF
  • Kazi M. Zakir Hossain1,
  • Uresha Patel1,
  • Ifty Ahmed*1,
  1. Bioengineering and Advanced Materials Research Group, University of Nottingham, Nottingham, NG7 2RD, GB
Cover Image

Published in Issue 2014-12-10

How to Cite

Hossain, K. M. Z., Patel, U., & Ahmed, I. (2014). Development of microspheres for biomedical applications: a review. Progress in Biomaterials, 4(1 (March 2015). https://doi.org/10.1007/s40204-014-0033-8
Crossref
Scopus
Google Scholar
Europe PMC

Abstract

Abstract An overview of microspheres manufactured for use in biomedical applications based on recent literature is presented in this review. Different types of glasses (i.e. silicate, borate, and phosphates), ceramics and polymer-based microspheres (both natural and synthetic) in the form of porous , non-porous and hollow structures that are either already in use or are currently being investigated within the biomedical area are discussed. The advantages of using microspheres in applications such as drug delivery, bone tissue engineering and regeneration, absorption and desorption of substances, kinetic release of the loaded drug components are also presented. This review also reports on the preparation and characterisation methodologies used for the manufacture of these microspheres. Finally, a brief summary of the existing challenges associated with processing these microspheres which requires further research and development are presented.

Keywords

  • Microspheres,
  • Porous,
  • Glasses,
  • Ceramics,
  • Polymers,
  • Tissue engineering and regenerative medicine
HTML PDF

References

  1. Abou Neel et al. (2008) Effect of increasing titanium dioxide content on bulk and surface properties of phosphate-based glasses (pp. 523-534) https://doi.org/10.1016/j.actbio.2007.11.007
  2. Abou Neel (2009) Doping of a high calcium oxide metaphosphate glass with titanium dioxide (pp. 991-1000) https://doi.org/10.1016/j.jnoncrysol.2009.04.016
  3. Abou Neel and Knowles (2008) Physical and biocompatibility studies of novel titanium dioxide doped phosphate-based glasses for bone tissue engineering applications (pp. 377-386) https://doi.org/10.1007/s10856-007-3079-5
  4. Abou Neel et al. (2009) Control of surface free energy in titanium doped phosphate based glasses by co-doping with zinc (pp. 392-407) https://doi.org/10.1002/jbm.b.31227
  5. Abou Neel et al. (2007) In vitro bioactivity and gene expression by cells cultured on titanium dioxide doped phosphate-based glasses (pp. 2967-2977) https://doi.org/10.1016/j.biomaterials.2007.03.018
  6. Ahmed et al. (2004) Phosphate glasses for tissue engineering: part 1. Processing and characterisation of a ternary-based P2O5–CaO–Na2O glass system (pp. 491-499) https://doi.org/10.1016/S0142-9612(03)00546-5
  7. Ahmed et al. (2004) Phosphate glasses for tissue engineering: part 2. Processing and characterisation of a ternary-based P2O5–CaO–Na2O glass fibre system (pp. 501-507) https://doi.org/10.1016/S0142-9612(03)00547-7
  8. Akamatsu et al. (2010) Three Preparation Methods for Monodispersed Chitosan Microspheres Using the Shirasu Porous Glass Membrane Emulsification Technique and Mechanisms of Microsphere Formation (pp. 3236-3241) https://doi.org/10.1021/ie901821s
  9. Athanasiou et al. (1998) Orthopaedic applications for PLA-PGA biodegradable polymers (pp. 726-737) https://doi.org/10.1016/S0749-8063(98)70099-4
  10. Auras et al. (2003) Mechanical, Physical, and Barrier Properties of Poly(Lactide) Films (pp. 123-135) https://doi.org/10.1177/8756087903039702
  11. Baldwin and Kiick (2010) Polysaccharide-Modified Synthetic Polymeric (pp. 128-140) https://doi.org/10.1002/bip.21334
  12. Bergquist et al. (1972) The manufacture of protein microspheres by suspension polymerization (pp. 791-799) https://doi.org/10.1159/000230895
  13. Berkland et al. (2004) Microsphere size, precipitation kinetics and drug distribution control drug release from biodegradable polyanhydride microspheres (pp. 129-141) https://doi.org/10.1016/j.jconrel.2003.09.011
  14. Blaine (1947) Experimental observations on absorbable alginate products in surgery (pp. 102-114) https://doi.org/10.1097/00000658-194701000-00011
  15. Bock et al. (2011) Electrospraying, a reproducible method for production of polymeric microspheres for biomedical applications (pp. 131-149) https://doi.org/10.3390/polym3010131
  16. Bohner et al. (2013) Synthesis of spherical calcium phosphate particles for dental and orthopedic applications https://doi.org/10.4161/biom.25103
  17. Cai et al. (2013) Porous microsphere and its applications (pp. 1111-1120) https://doi.org/10.2147/IJN.S41271
  18. Chan et al. (2002) Production of alginate microspheres by internal gelation using an emulsification method (pp. 259-262) https://doi.org/10.1016/S0378-5173(02)00170-9
  19. Chen et al. (2006) The use of poly(l-lactide) and RGD modified microspheres as cell carriers in a flow intermittency bioreactor for tissue engineering cartilage (pp. 4453-4460) https://doi.org/10.1016/j.biomaterials.2006.04.011
  20. Chen et al. (2011) A modular approach to the engineering of a centimeter-sized bone tissue construct with human amniotic mesenchymal stem cells-laden microcarriers (pp. 7532-7542) https://doi.org/10.1016/j.biomaterials.2011.06.054
  21. Cho et al. (2010) Synthesis of nano-sized biphasic calcium phosphate ceramics with spherical shape by flame spray pyrolysis (pp. 1143-1149) https://doi.org/10.1007/s10856-009-3980-1
  22. Choi et al. (2010) Uniform beads with controllable pore sizes for biomedical applications (pp. 1492-1498) https://doi.org/10.1002/smll.201000544
  23. Choi et al. (2012) Biodegradable porous beads and their potential applications in regenerative medicine (pp. 11442-11451) https://doi.org/10.1039/c2jm16019f
  24. Chung et al. (2001) Effects of the rate of solvent evaporation on the characteristics of drug loaded PLLA and PDLLA microspheres (pp. 161-169) https://doi.org/10.1016/S0378-5173(00)00574-3
  25. Chung et al. (2011) Novel scaffold design with multi-grooved PLA fibers https://doi.org/10.1088/1748-6041/6/4/045001
  26. Conzone and Day (2009) Preparation and properties of porous microspheres made from borate glass (pp. 531-542) https://doi.org/10.1002/jbm.a.31883
  27. Conzone et al. (2002) In vitro and in vivo dissolution behavior of a dysprosium lithium borate glass designed for the radiation synovectomy treatment of rheumatoid arthritis (pp. 260-268) https://doi.org/10.1002/jbm.10047
  28. Conzone et al. (2004) Biodegradable radiation delivery system utilizing glass microspheres and ethylene diaminetetraacetate chelation therapy (pp. 256-264) https://doi.org/10.1002/jbm.a.30076
  29. Day et al. (2003) Transformation of borate glasses into biologically useful materials (pp. 75-81)
  30. d’Ayala et al. (2008) Marine derived polysaccharides for biomedical applications: chemical modification approaches (pp. 2069-2106) https://doi.org/10.3390/molecules13092069
  31. Dhawan and Singla (2003) Nifedipine loaded chitosan microspheres prepared by emulsification phase-separation (pp. 243-254) https://doi.org/10.1080/10520290310001602396
  32. Edlund U, Albertsson AC (2002) degradable polymer microspheres for controlled drug delivery. In: degradable aliphatic polyesters, vol 157 Advances in Polymer Science. Springer, New York pp 67–112
  33. Ehtezazi and Washington (2000) Controlled release of macromolecules from PLA microspheres: using porous structure topology (pp. 361-372) https://doi.org/10.1016/S0168-3659(00)00270-4
  34. Eiselt et al. (2000) Porous carriers for biomedical applications based on alginate hydrogels (pp. 1921-1927) https://doi.org/10.1016/S0142-9612(00)00033-8
  35. Felfel et al. (2011) In vitro degradation, flexural, compressive and shear properties of fully bioresorbable composite rods (pp. 1462-1472) https://doi.org/10.1016/j.jmbbm.2011.05.016
  36. Freiberg and Zhu (2004) Polymer microspheres for controlled drug release (pp. 1-18) https://doi.org/10.1016/j.ijpharm.2004.04.013
  37. Fu et al. (2010) Effect of process variables on the microstructure of hollow hydroxyapatite microspheres prepared by a glass conversion method (pp. 3116-3123) https://doi.org/10.1111/j.1551-2916.2010.03833.x
  38. Fu et al. (2012) Long-term conversion of 45S5 bioactive glass-ceramic microspheres in aqueous phosphate solution (pp. 1181-1191) https://doi.org/10.1007/s10856-012-4605-7
  39. Han et al. (2008) Stability and size dependence of protein microspheres prepared by ultrasonication (pp. 5162-5166) https://doi.org/10.1039/b807615d
  40. Hench (2006) The story of Bioglass (R) (pp. 967-978) https://doi.org/10.1007/s10856-006-0432-z
  41. Hong et al. (2005) Preparation of porous polylactide microspheres by emulsion-solvent evaporation based on solution induced phase separation (pp. 622-627) https://doi.org/10.1002/pat.629
  42. Hong et al. (2011) Drug-loaded porous spherical hydroxyapatite granules for bone regeneration (pp. 349-355) https://doi.org/10.1007/s10856-010-4197-z
  43. Hong et al. (2012) Collagen microsphere production on a chip (pp. 3277-3280) https://doi.org/10.1039/c2lc40558j
  44. Hossain et al. (2012) Physico-chemical and mechanical properties of nanocomposites prepared using cellulose nanowhiskers and poly(lactic acid) (pp. 2675-2686) https://doi.org/10.1007/s10853-011-6093-4
  45. Hossain et al. (2014) Effect of cellulose nanowhiskers on surface morphology mechanical properties, and cell adhesion of melt-drawn polylactic acid fibers (pp. 1498-1506) https://doi.org/10.1021/bm5001444
  46. Hossain KMZ, Muhammad Sami H, Reda F, Ifty A (2014b) Development of phosphate-based glass fibers for biomedical applications. In: Hot Topics in Biomaterials. Future Science Book Series. Future Science Ltd, pp 104–115
  47. Hossain et al. (2014) Mechanical, crystallisation and moisture absorption properties of melt drawn polylactic acid fibres (pp. 270-281) https://doi.org/10.1016/j.eurpolymj.2014.02.001
  48. Hu et al. (2014) Modified composite microspheres of hydroxyapatite and poly(lactide-co-glycolide) as an injectable scaffold (pp. 764-772) https://doi.org/10.1016/j.apsusc.2013.12.045
  49. Huang et al. (2009) Strength of hollow hydroxyapatite microspheres prepared by a glass conversion process (pp. 123-129) https://doi.org/10.1007/s10856-008-3554-7
  50. Izumikawa et al. (1991) Preparation of poly(l-lactide) microspheres of different crystalline morphology and effect of crystalline morphology on drug release rate (pp. 133-140) https://doi.org/10.1016/0168-3659(91)90071-K
  51. Jones (2013) Review of bioactive glass: from hench to hybrids (pp. 4457-4486) https://doi.org/10.1016/j.actbio.2012.08.023
  52. Jung et al. (2000) Sulfobutylated poly(vinyl alcohol)-graft-poly(lactide-co-glycolide)s facilitate the preparation of small negatively charged biodegradable nanospheres (pp. 157-169) https://doi.org/10.1016/S0168-3659(00)00201-7
  53. Jung et al. (2002) Loading of tetanus toxoid to biodegradable nanoparticles from branched Poly(Sulfobutyl-Polyvinyl Alcohol)-g-(Lactide-Co-Glycolide) nanoparticles by protein adsorption: a mechanistic study (pp. 1105-1113) https://doi.org/10.1023/A:1019833822997
  54. Kawashita et al. (2003) Preparation of antibacterial silver-doped silica glass microspheres (pp. 266-274) https://doi.org/10.1002/jbm.a.10547
  55. Kawanobe Y, Honda M, Konishi T, Mizumoto M, Habuto Y, Kanzawa N, Uchino T, Aizawa M (2010) Preparation of apatite microsphere with nano-size pores on the surface via salt-assisted ultrasonic spray-pyrolysis technique and its Drug Release Behavior. J Aust Ceram Soc 46(2):6–10
  56. Khorasani et al. (2008) Plasma surface modification of poly (l-lactic acid) and poly (lactic-co-glycolic acid) films for improvement of nerve cells adhesion (pp. 280-287) https://doi.org/10.1016/j.radphyschem.2007.05.013
  57. Kim K, Pack D (2006) Microspheres for drug delivery. In: Ferrari M, Lee A, Lee LJ (eds) BioMEMS and Biomedical Nanotechnology. Springer, US pp 19–50
  58. Knowles (2003) Phosphate based glasses for biomedical applications (pp. 2395-2401) https://doi.org/10.1039/b307119g
  59. Kohane et al. (2006) Biodegradable polymeric microspheres and nanospheres for drug delivery in the peritoneum (pp. 351-361) https://doi.org/10.1002/jbm.a.30654
  60. Komlev et al. (2002) A method to fabricate porous spherical hydroxyapatite granules intended for time-controlled drug release (pp. 3449-3454) https://doi.org/10.1016/S0142-9612(02)00049-2
  61. Lakhkar (2012) Titanium phosphate glass microspheres for bone tissue engineering (pp. 4181-4190) https://doi.org/10.1016/j.actbio.2012.07.023
  62. Leenslag and Pennings (1987) High-strength poly(l-lactide) fibres by a dry-spinning/hot-drawing process (pp. 1695-1702) https://doi.org/10.1016/0032-3861(87)90012-7
  63. Lemoine et al. (1998) Preparation and characterization of alginate microspheres containing a model antigen (pp. 9-19) https://doi.org/10.1016/S0378-5173(98)00303-2
  64. Li (2010) Porous-wall hollow glass microspheres as novel potential nanocarriers for biomedical applications (pp. 127-136) https://doi.org/10.1016/j.nano.2009.06.004
  65. Lin et al. (1999) A novel fabrication of poly(ɛ-caprolactone) microspheres from blends of poly(ɛ-caprolactone) and poly(ethylene glycol)s (pp. 1731-1735) https://doi.org/10.1016/S0032-3861(98)00378-4
  66. Lin et al. (2014) Preparation of PLLA/bpV(pic) microspheres and their effect on nerve cells (pp. 76-80) https://doi.org/10.1007/s11596-014-1234-z
  67. Liu (1996) Fabrication and characterization of porous hydroxyapatite granules (pp. 1955-1957) https://doi.org/10.1016/0142-9612(95)00301-0
  68. Liu (2012) Preparation of porous hollow SiO2 spheres by a modified stober process using MF microspheres as templates (pp. 273-285) https://doi.org/10.1007/s10876-011-0427-x
  69. Luciani et al. (2008) PCL microspheres based functional scaffolds by bottom-up approach with predefined microstructural properties and release profiles (pp. 4800-4807) https://doi.org/10.1016/j.biomaterials.2008.09.007
  70. Maeng et al. (2010) Culture of human mesenchymal stem cells using electrosprayed porous chitosan microbeads (pp. 869-876) https://doi.org/10.1002/jbm.a.32417
  71. Martinelli et al. (2010) Synthesis and characterization of glass-ceramic microspheres for thermotherapy (pp. 2683-2688) https://doi.org/10.1016/j.jnoncrysol.2010.05.006
  72. Martinsen et al. (1989) Alginate as immobilization material: I Correlation between chemical and physical properties of alginate gel beads (pp. 79-89) https://doi.org/10.1002/bit.260330111
  73. Mofidi et al. (2000) Mass preparation and characterization of alginate microspheres (pp. 885-888) https://doi.org/10.1016/S0032-9592(99)00149-1
  74. Montjovent (2005) Biocompatibility of bioresorbable poly(l-lactic acid) composite scaffolds obtained by supercritical gas foaming with human fetal bone cells (pp. 1640-1649) https://doi.org/10.1089/ten.2005.11.1640
  75. Morrow et al. (1974) In vivo comparison of polyglycolic acid, chromic catgut and silk in tissue of the genitourinary tract: an experimental study of tissue retrieval and calculogenesis (pp. 655-658)
  76. Nagai et al. (2010) Preparation and characterization of collagen microspheres for sustained release of VEGF (pp. 1891-1898) https://doi.org/10.1007/s10856-010-4054-0
  77. Oh et al. (2011) Preparation of budesonide-loaded porous PLGA microparticles and their therapeutic efficacy in a murine asthma model (pp. 56-62) https://doi.org/10.1016/j.jconrel.2010.11.001
  78. Oliveira et al. (2005) Spray-dried chitosan microspheres cross-linked with d, l-glyceraldehyde as a potential drug delivery system: preparation and characterization (pp. 353-360) https://doi.org/10.1590/S0104-66322005000300004
  79. Paul and Sharma (1999) Development of porous spherical hydroxyapatite granules: application towards protein delivery (pp. 383-388) https://doi.org/10.1023/A:1008918412198
  80. Perez et al. (2011) Porous hydroxyapatite and gelatin/hydroxyapatite microspheres obtained by calcium phosphate cement emulsion (pp. 156-166) https://doi.org/10.1002/jbm.b.31798
  81. Perez et al. (2014) Therapeutic bioactive microcarriers: co-delivery of growth factors and stem cells for bone tissue engineering (pp. 520-530) https://doi.org/10.1016/j.actbio.2013.09.042
  82. Qiu et al. (2008) Biomimetic synthesis of spherical nano-hydroxyapatite with polyvinylpyrrolidone as template (pp. 612-617) https://doi.org/10.1179/174328407X176974
  83. Rahaman et al. (2011) Bioactive glass in tissue engineering (pp. 2355-2373) https://doi.org/10.1016/j.actbio.2011.03.016
  84. Ribeiro et al. (2005) Chitosan-reinforced alginate microspheres obtained through the emulsification/internal gelation technique (pp. 31-40) https://doi.org/10.1016/j.ejps.2005.01.016
  85. Ribeiro CC, Barrias CC, Barbosa MA (2006) Preparation and characterisation of calcium-phosphate porous microspheres with a uniform size for biomedical applications. J Mater Sci Mater Med 17(5):455–463. doi:
  86. 10.1007/s10856-006-8473-x
  87. Ruan and Feng (2003) Preparation and characterization of poly(lactic acid)–poly(ethylene glycol)–poly(lactic acid) (PLA–PEG–PLA) microspheres for controlled release of paclitaxel (pp. 5037-5044) https://doi.org/10.1016/S0142-9612(03)00419-8
  88. Sene et al. (2008) Synthesis and characterization of phosphate glass microspheres for radiotherapy applications (pp. 4887-4893) https://doi.org/10.1016/j.jnoncrysol.2008.04.041
  89. Stöber et al. (1968) Controlled growth of monodisperse silica spheres in the micron size range (pp. 62-69) https://doi.org/10.1016/0021-9797(68)90272-5
  90. Sui (2013) Synthesis of mesoporous calcium phosphate microspheres by chemical transformation process: their stability and encapsulation of carboxymethyl chitosan (pp. 3201-3207) https://doi.org/10.1021/cg400595s
  91. Tao Y, Zhang HL, Hu YM, Wan S, Su ZQ (2013) Preparation of Chitosan and Water-Soluble Chitosan Microspheres via Spray-Drying Method to Lower Blood Lipids in Rats Fed with High-Fat Diets. Int J Mol Sci 14(2):4174–4184
  92. Todea et al. (2013) XPS analysis of aluminosilicate microspheres bioactivity tested in vitro (pp. 777-783) https://doi.org/10.1016/j.apsusc.2013.01.178
  93. Torres et al. (2007) Production of chemically modified chitosan microspheres by a spraying and coagulation method (pp. 347-352) https://doi.org/10.1590/S1516-14392007000400005
  94. Ungaro et al. (2009) Insulin-loaded PLGA/cyclodextrin large porous particles with improved aerosolization properties: in vivo deposition and hypoglycaemic activity after delivery to rat lungs (pp. 25-34) https://doi.org/10.1016/j.jconrel.2008.12.011
  95. Wan et al. (1992) Drug encapsulation in alginate microspheres by emulsification (pp. 309-316) https://doi.org/10.3109/02652049209021245
  96. Wang et al. (2002) Characterization of the initial burst release of a model peptide from poly(d, l-lactide-co-glycolide) microspheres (pp. 289-307) https://doi.org/10.1016/S0168-3659(02)00137-2
  97. Wang et al. (2004) Preparation, characterization, and in vitro evaluation of physostigmine-loaded poly(ortho ester) and poly(ortho ester)/poly(d, l-lactide-co-glycolide) blend microspheres fabricated by spray drying (pp. 3275-3282) https://doi.org/10.1016/j.biomaterials.2003.09.099
  98. Wang et al. (2006) Preparation of hollow hydroxyapatite microspheres (pp. 641-646) https://doi.org/10.1007/s10856-006-9227-5
  99. Wang et al. (2007) Preparation of hollow porous HAP microspheres as drug delivery vehicles (pp. 174-177) https://doi.org/10.1007/s11595-005-1174-3
  100. Waris et al. (2004) Use of Bioabsorbable Osteofixation Devices in the Hand (pp. 590-598) https://doi.org/10.1016/j.jhsb.2004.02.005
  101. Xia et al. (2013) Controlled protein release from monodisperse biodegradable double-wall microspheres of controllable shell thickness (pp. 707-714) https://doi.org/10.1016/j.jconrel.2013.08.009
  102. Yang et al. (2009) Development of highly porous large PLGA microparticles for pulmonary drug delivery (pp. 1947-1953) https://doi.org/10.1016/j.biomaterials.2008.12.044
  103. Yao et al. (2013) Collagen microsphere serving as a cell carrier supports oligodendrocyte progenitor cell growth and differentiation for neurite myelination in vitro https://doi.org/10.1186/scrt320
  104. Zhao et al. (2004) Preparation of DNA-loaded polysulfone microspheres by liquid–liquid phase separation and its functional utilization (pp. 470-476) https://doi.org/10.1016/j.jcis.2004.02.079
  105. Zielhuis et al. (2006) Holmium-Loaded Poly(l-lactic Acid) microspheres: in vitro degradation study (pp. 2217-2223) https://doi.org/10.1021/bm060230r