Abstract
Background: Polymethyl Methacrylate (PMMA) bone cement is the clinical gold standard
biomaterial for local antibiotic therapy in osteomyelitis. However, it releases 50% of the antibiotic
within the first three days. It generates excessive heat during polymerization and is non-biodegradable.
It must be removed by another operation. The best-known alternative for PMMA is hydroxyapatite.
Objectives: The present patented work is focused on synthesizing the biodegradable hydroxyapatite in
nano form for slow and sustained release of antibiotics and studying the release kinetics of antibiotics.
Methods: Nano-hydroxyapatite was synthesized by co-precipitation method and characterized by particle
size analyser, transmission electron microscopy, fourier transform infrared spectroscopy and energy
dispersive X-Ray analysis. Antibiotic loaded nano-hydroxyapatite was prepared as 7 mm beads.
The efficiency of drug-loaded nano-hydroxyapatite beads against osteomyelitic isolates was evaluated
by well diffusion assay. Zero-order, first order, second order, Higuchi model, Korsmeyer-Peppas and
Gompertz models were fit into the release kinetics of antibiotics from hydroxyapatite.
Results: Average size of nano-hydroxyapatite was 5 nm. The bactericidal activity exhibited by antibiotic-
loaded micro-sized hydroxyapatite was therapeutic until 10 days only, whereas antibiotic-loaded
nano-hydroxyapatite was therapeutic until 8 weeks. This confirms the burst release of antibiotics from
micro-sized hydroxyapatite beads. In contrast, the release was slow and sustained up to 8 weeks from
nano-hydroxyapatite. Korsmeyer-Peppas model fits into the release kinetics of antibiotics from nanohydroxyapatite.
Conclusion: Nano-hydroxyapatite with a Ca/P ratio of 1.78 is suitable for the slow and sustained delivery
of antibiotics for 8 weeks.
Keywords:
Antibiotics, bactericidal activity, bone cement, Gompertz model, Korsmeyer-Peppas model, nano-hydroxyapatite.
Graphical Abstract
[5]
Moralle MR, Stekas NR. Salvage of a below knee amputation utilizing rotationplasty principles in a patient with chronic tibial osteomyelitis. J Orthop Case Rep 2016; 6: 57-62.
[11]
Kevin K. Current insights on antibiotic-loaded cement and the use of bioceramics in diabetic limb salvage. Diabetes Watch 2018; 31(10): 12-8.
[23]
Vukomanovic M. Skapin, Sreco Davor, Suvorov, Danilo, Inventorfunotion Alized Hydroxyapatite/Gold Composites As “Green” materials with antibacterial activity and the process for preparing and use 2013. THEREOF 2013; p. 19. [Accessed 19 December 2013.
[42]
Engin A, Girgin İ. Synthesis of hydroxyapatite by using calcium carbonate and phosphoric acid in various water-ethanol solvent systems. Cent J Chem 2009; 7: 745-51.
[43]
Narashimhan B. MSK, Peppas NA Encyclopedia of controlled drug delivery. New york: John Wiley and Sons 1999.
[47]
Baker RW, Sanders LM. Controlled release delivery systems synthetic membranes: Science, engineering and applications 181. Dordrecht: Springer 1986; pp. 581-624.
[53]
Hadeel AJLE, Rohanizadeh R, Coster H, Dehghani F. preparation of nanostructured hydroxyapatite in organic solvents forclinical applications. Trends Biomater Artif Organs 2011; 25(1): 12-9.
[54]
Peng XG. Mechanisms for the shape-control and shape-evolution of colloidal semiconductor nanocrystals. Adv Mater 2003; 15: 459-63.
[55]
Pu’ad NASM, Koshy P, Abdullah HZ, Idris MI, Lee TC. Review Article-syntheses of hydroxyapatite from natural sources. Heliyon 2019; 5(5)e01588
[60]
Adak MD, Purohit KM. Synthesis of nano-crystalline hydroxyapatite from dead snail shells for biological implantation. Trends Biomater Artif Organs 2011; 25(3): 101-6.
[62]
Bilal H, Hasan F, Bilal S. Susceptibility pattern of pseudomonas aeruginosa against various antibiotics along with computational analysis. Int J Sci Basic Appl Res 2015; 24: 23-45.
[64]
Adedeji AB, Abdulkadir AO. Etiology and antimicrobial resistance pattern of bacterial agents of urinary tract infections in students of tertiary institutions in Yola Metropolis. Adv Biol Res 2009; 3: 67-70.
[77]
Schindler KM, Wayne F, Smith DB. , Warsaw. Biomet Manufacturing, LLC, Warsaw, assignee. Antimicrobial methacrylate cements. US Patent 13/313,764,. 2014.
[78]
David M. Queen's University At Kingston, Assignee. Anaesthetic bone cement. US patent US 2002/0137813 A1, . 2002.
[79]
Brian R. University of South Carolina, Columbia, SC (US), assignee bocompatible cement containing reactive calcum phosphate nanoparticles and methods for making and using such cement. 2009.
[80]
Thomas JGM, Lars ET, Steen SSM, Rosengren S. Biomet SAS (FR), assignee method and apparatus for delivery of bone cement. 2016.
[81]
Lu Donghui, Shuxin Zhou S. high strength biological cement composition and using the same. 2009.