Synthesis of nanosized hydroxyapatite/agarose powders for bone filler and drug delivery application

Abstract Drug-loaded bioactive composite powders are used for the treatment of orthopedic diseases and prevention of infection or inflammatory reaction after surgical implantation. Nanosized (80 × 23 nm 2 ) and porous (17 ± 1 nm) hydroxyapatite (HAp)/agarose composite rods were prepared by sol-gel synthesis and subjected to microwave and conventional heating. Microwave heating increased the degree of crystallinity and the thermal stability and produced calcium-deficient HAp/agarose composite powders. There was a considerable reduction (by 39%) in the size of rods on microwave heating whereas the conventional heating at 700 °C rendered the samples porous and agglomerated with a significant decrease in the specific surface area. The agarose contents in as-synthesized and microwave heated samples were ∼14% and 4%, respectively. The samples were partially degradable upon immersion in SBF, and later exhibited calcium phosphate deposition which was confirmed by gravimetry. An antibiotic (amoxicillin) and anticancer (5-fluorouracil) drug-loaded microwave-heated nanosized HAp/agarose composite powder gave an extended drug release when compared to the as-synthesized and the conventionally heated samples. The composite powders showed a negative zeta potential, hemocompatibility and better antimicrobial efficacy than pure HAp (conventional heated sample). The microwave heating retained the organic phase (agarose) along with a reduction in particle size. In addition, this technique is simple, fast and cost-effective to produce mesoporous, bioactive and resorbable nanocomposite (HAp/agarose) powders which could find application as bone filling materials and drug delivery systems.

[1]  J. Vörös,et al.  Microarrays made easy: biofunctionalized hydrogel channels for rapid protein microarray production. , 2011, ACS applied materials & interfaces.

[2]  C. Pineda,et al.  Imaging of osteomyelitis: current concepts. , 2006, Infectious disease clinics of North America.

[3]  C. Betzel,et al.  Synthesis of stoichiometric nano crystalline hydroxyapatite by ethanol-based sol–gel technique at low temperature , 2004 .

[4]  N. Davidenko,et al.  Chitosan/hydroxyapatite-based composites , 2010 .

[5]  M. Akashi,et al.  Osteoconductive and hemostatic properties of apatite formed on/in agarose gel as a bone-grafting material. , 2003, Journal of biomedical materials research. Part B, Applied biomaterials.

[6]  Liang Hao,et al.  On the correlation between Nd:YAG laser-induced wettability characteristics modification and osteoblast cell bioactivity on a titanium alloy , 2006 .

[7]  T. Kissel,et al.  Controlled release of gentamicin from calcium phosphate-poly(lactic acid-co-glycolic acid) composite bone cement. , 2006, Biomaterials.

[8]  Tadashi Kokubo,et al.  How useful is SBF in predicting in vivo bone bioactivity? , 2006, Biomaterials.

[9]  C. V. van Blitterswijk,et al.  Hydroxylapatite/poly(L-lactide) composites: an animal study on push-out strengths and interface histology. , 1993, Journal of biomedical materials research.

[10]  María Vallet-Regí,et al.  New developments in ordered mesoporous materials for drug delivery , 2010 .

[11]  S. Kalkura,et al.  Surfactant free rapid synthesis of hydroxyapatite nanorods by a microwave irradiation method for the treatment of bone infection , 2011, Nanotechnology.

[12]  S. Kalkura,et al.  In vitro sustained release of amoxicillin from lanthanum hydroxyapatite nano rods , 2011 .

[13]  R. Holmes,et al.  Porous hydroxylapatite as a bone graft substitute in mandibular contour augmentation: a histometric study. , 1987, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[14]  A. Metters,et al.  Hydrogels in controlled release formulations: network design and mathematical modeling. , 2006, Advanced drug delivery reviews.

[15]  I. O. Smith,et al.  Electrostatic interactions as a predictor for osteoblast attachment to biomaterials. , 2004, Journal of biomedical materials research. Part A.

[16]  M. Vallet‐Regí,et al.  An optimized β‐tricalcium phosphate and agarose scaffold fabrication technique , 2008 .

[17]  R. Franke,et al.  Calcium phosphate granules for use as a 5-Fluorouracil delivery system , 2009 .

[18]  J. Haber,et al.  Manual on catalyst characterization (Recommendations 1991) , 1991 .

[19]  M. Vallet‐Regí,et al.  Room temperature synthesis of agarose/sol-gel glass pieces with tailored interconnected porosity. , 2006, Journal of biomedical materials research. Part A.

[20]  M. Akashi,et al.  Regenerative behavior of biomineral/agarose composite gels as bone grafting materials in rat cranial defects. , 2009, Journal of biomedical materials research. Part A.

[21]  Byung-Soo Kim,et al.  A poly(lactide-co-glycolide)/hydroxyapatite composite scaffold with enhanced osteoconductivity. , 2007, Journal of biomedical materials research. Part A.

[22]  M. Epple,et al.  Lanthanide-doped calcium phosphate nanoparticles with high internal crystallinity and with a shell of DNA as fluorescent probes in cell experiments , 2007 .

[23]  Huang-Hao Yang,et al.  Flow injection fluorescence immunoassay for gentamicin using sol-gel-derived mesoporous biomaterial. , 2002, Analytical biochemistry.

[24]  P. Xiao,et al.  Effects of solvents on properties of nanocrystalline hydroxyapatite produced from hydrothermal process , 2006 .

[25]  C. Satriano,et al.  Characterization and cytocompatibility of hybrid aminosilane-agarose hydrogel scaffolds , 2010, Biointerphases.

[26]  Jueren Lou,et al.  Evaluation of different scaffolds for BMP-2 genetic orthopedic tissue engineering. , 2005, Journal of biomedical materials research. Part B, Applied biomaterials.

[27]  M Epple,et al.  A novel method to produce hydroxyapatite objects with interconnecting porosity that avoids sintering. , 2004, Biomaterials.

[28]  S. Kalkura,et al.  Fibrous growth of strontium substituted hydroxyapatite and its drug release , 2011 .

[29]  María Vallet-Regí,et al.  Mesoporous materials for drug delivery. , 2007, Angewandte Chemie.

[30]  T. Kumar,et al.  Strontium‐Substituted Calcium Deficient Hydroxyapatite Nanoparticles: Synthesis, Characterization, and Antibacterial Properties , 2012 .

[31]  R. Mythili,et al.  Blood compatibility of iron-doped nanosize hydroxyapatite and its drug release. , 2012, ACS applied materials & interfaces.

[32]  Louis Pasteur,et al.  XRDA: a program for energy-dispersive X-ray diffraction analysis on a PC. By SERGE DESGRENIERS , 1994 .

[33]  S. Mallapragada,et al.  Aqueous Route Synthesis of Mesoporous ZrO2 by Agarose Templation , 2012 .

[34]  J. Forsythe,et al.  Effects of calcination temperature on the drug delivery behaviour of Ibuprofen from hydroxyapatite powders , 2008, Journal of materials science. Materials in medicine.

[35]  E. Landi,et al.  Densification behaviour and mechanisms of synthetic hydroxyapatites , 2000 .

[36]  K. Asokan,et al.  Enhancement of wettability and antibiotic loading/release of hydroxyapatite thin film modified by 100 MeV Ag7+ ion irradiation , 2012 .

[37]  R. Caruso,et al.  Agarose template for the fabrication of macroporous metal oxide structures. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[38]  K. P. Rao,et al.  Preparation, characterization, and in vitro release of gentamicin from coralline hydroxyapatite-alginate composite microspheres. , 2003, Journal of biomedical materials research. Part A.

[39]  Jean-Christophe Leroux,et al.  Biomedical applications of bisphosphonates. , 2013, Journal of controlled release : official journal of the Controlled Release Society.

[40]  W. Bonfield,et al.  Biodegradable drug delivery system for the treatment of bone infection and repair , 1999, Journal of materials science. Materials in medicine.

[41]  J R van Horn,et al.  Backgrounds of antibiotic-loaded bone cement and prosthesis-related infection. , 2004, Biomaterials.

[42]  S. Chueh,et al.  Microspheres of hydroxyapatite/reconstituted collagen as supports for osteoblast cell growth. , 1999, Biomaterials.

[43]  K. Pal,et al.  Development of Porous Hydroxyapatite Scaffolds , 2006 .

[44]  M. Palanichamy,et al.  A novel technique to synthesize hydroxyapatite at low temperature , 2003 .

[45]  H. Varma,et al.  A triphasic ceramic-coated porous hydroxyapatite for tissue engineering application. , 2008, Acta biomaterialia.