Fabrication of cefuroxime-impregnated calcium sulfate: Polycaprolactone composite implant for osteomyelitis

Himanshu Gupta, Anubhav Anand1, Rakesh Pundir, C S Pandian, Shubhini Saraf

Abstract


Osteomyelitis is characterized as an inflammatory bone disease caused by pyrogenic bacteria. As oral bioavailabilities of antibiotics are low, a regimen of 6 weeks of intravenous antibiotic is necessary for adequate therapy. Although the
dose of antibiotic administered systemically is high, therapeutically effective drug concentrations are not always achieved at the site of infection. This problem can be overcome by the use of local antibiotics from a biodegradable implant for chronic osteomyelitis that can deliver the drug at least for 6 weeks.The implant delivers high antibiotic concentration at tissue levels, obliterates dead space, aids bone repair and does not need to be removed. The aim of this study was to develop and evaluate a calcium sulfate and polycaprolactone (PCL)-based composite biodegradable implantable delivery system of cefuroxime for
the localized treatment of osteomyelitis that can deliver the drug for at least 6 weeks.The PCL and calcium sulfate composite system has not been studied yet. Interaction studies were carried out to check any incompatibility between the ingredients. Implants were prepared by a modified fabrication technique to avoid solvent use. The prepared implants were evaluated for various in vitro parameters like dimensions, hardness, tensile strength, drug release profile, sterility test and morphological changes in pellet before and after drug release. The pellets were also tested for microbiological efficacy and compared with a plain drug solution in different concentrations. Developed pellets are regular in shape and size with good tensile strength. The release profile displayed drug levels above the minimum inhibitory concentration continuously for up to 2 months.
A wide zone of inhibition by the pellet against Staphylococcus aureus as compared with the drug solution proves its efficacy in the treatment of osteomyelitis. Results show that the developed calcium sulfate and PCL-based composite biodegradable implantable delivery system of cefuroxime is a good alternate system and can deliver the drug for more than 6 weeks,
maintaining an adequate inhibitory concentration at the site.


Full Text:

PDF

References


Tortoara GJ, Derrickson B. Ch 6. The Skeletal System: Bone Tissue.

In Principles of Anatomy and Physiology. 11th ed. Wiley International;

p. 190.

Gitelis S, Brebach GT. The treatment of chronic osteomyelitis with

a biodegradable antibiotic impregnated implant. J Orthop Surg (Hong

Kong) 2002;10:53-60.

Hanssen AD. Local antibiotic delivery vehicle in the treatment

of musculoskeletal infection. Session IV. Clin Orthop Relat Res

;437:91-6.

Gao C, Gao J, You X, Huo S, Li X, Zhang Y, et al. Fabrication of calcium

sulfate/PLLA composite for bone Repair. J Biomed Mater Res A

;73A:244-53.

Walsh D, Furuzono T, Tanaka J. Preparation of porous composite

implant materials by in situ polymerization of porous apatite containing

ε-caprolactone or methyl methacrylate. Biomaterial 2001;21:1205-12.

Sato S, Koshino T, Saito T. Osteogenic response of rabbit tibia

to hydroxyapatite particle: Plaster of Paris mixture. Biomaterial

;19:1895-900.

Georgiade NG, Hanker J, Levin S, Ruff G. The use of particular

hydroxyapatite and Plaster of Paris in aesthetic and reconstructive

surgery. Aesthetic Plast Surg 1993;17:5-92.

Khairoun I, Boltong MG, Driessens FC, Planell JA. Effect of calcium

carbonate on the compliance of apatitic calcium phosphate bone

cement. Biomaterial 1997;18:1535-9.

Higashi S, Yamamuro T, Nakamura T, Ikada Y, Hyon SH, Jamshidi K.

Polymer-hydroxyapatite composites for biodegradable bone fillers.

Biomaterial 1986;7:183-7.

Chen G, Ushida T, Tateishi T. Poly (DL-lactic-co-glycolic acid) sponge

hybridized with collagen microspongea and deposited apatite

particulates. J Biomed Mater Res 2001;57:8-14.

Bakos D, Soldán M, Hernández-Fuentes I. Hydroxyapatite- ollagen- yaluronic ch acid composite. Biomaterial 1999;20:191-5.

Tamura H, Tokma S. Carboxymethyl-chitin and hydroxyapatite

composite for bone repairing. Polymer Preprints 2000;41:1032–3.

Coetzee AS. Regeneration of bone in the presence of calcium sulfate.

Arch Otolaryngol 1980;106:405-9.

Laurencin CT, Ambrosio AM, Borden MD, Cooper JA Jr. Tissue

engineering: Orthopaedic applications. Annu Rev Biomed Eng

;1:19-46.

Orsini G, Ricci J, Scarano A, Pecora G, Petrone G, Piattelli A. Bone- defect healing with calcium-sulfate particles and cement: An experimental

study in rabbit. J Biomed Mater Res B Appl Biomater 2004;68:199-208.

Ziran BH, Smith WR, Morgan SJ. Use of calcium-based demineralized

bone matrix/allograft for nonunions and posttraumatic reconstruction

of the appendicular skeleton: Preliminary results and complications.

J Trauma 2007;63:1324-8.

Harris RJ. Clinical evaluation of a composite bone graft with a calcium

sulfate barrier. J Periodontol 2004;75:685-92.

La Gatta A, De Rosa A, Laurienzo P, Malinconico M, De Rosa M,

Schiraldi C. A Novel Injectable Poly(epsilon-caprolactone)/Calcium

Sulfate System for Bone Regeneration: Synthesis and Characterization.

Macromol Biosci 2005;5:1108-17.

Gao C, Huo S, Li X, You X, Zhang Y, Gao J. Characteristics of calcium

sulfate/gelatin composite biomaterials for bone repair. J Biomater Sci

Polym Ed 2007;18:799-824.

A. grawal CM, Ray RB. Biodegradable polymeric scaffolds for

musculoskeletal tissue engineering. J Biomed Mater Res 2001;55:141- 0.

Mano JF, Sousa RA, Boesel LF, Neves NM, Reis RL. Bioinert, biodegradable

and injectable polymeric matrix composites for hard tissue replacement:

State of the art and recent developments. Composites Science and

Technology 2004; 64: 789-817.

Overbeck JP, Winckler ST, Meffert R, Törmälä P, Spiegel HU, Brug E.

Penetration of ciprofloxacin into bone: A new bioabsorbable implant.

J Invest 1995;8:155-62.

Ramchandani M, Robinson D. In vitro in vivo release of ciprofloxacin

from PLGA 50:50 implants. J Control Rel 1998;54:167-75.

Désévaux C, Lenaerts V, Girard C, Dubreuil P. Characterization of

crosslinked high amylase starch matrix implants: In vivo release of

ciprofloxacin. J Control Rel 2002;82:95-103.

Désévaux C, Dubreuil P, Lenaerts V. Characterization of crosslinked

high amylase starch matrix implants: In vitro release of ciprofloxacin.

J Control Rel 2002;82:83–93.

El-Kamel AH, Baddour MM. Gatifloxacin Biodegradable Implant for

Treatment of Experimental Osteomyelitis: In vitro and in vivo Evaluation.

Drug Deliv 2007;14:349-56.

Shinto Y, Uchida A, Korkusuz F, Araki N, Ono K. Calcium hydroxyapatite

ceramic used as a delivery system for antibiotics. J Bone Joint Surg Br

;74B:600-4.

Bálint L, Kocsis B, Szántó Z, Szabó G. In vitro measurement of the time

related efficacy of gentamicin sulfate release from bone cements.

Chemotherapy 2004;50:302-7.




DOI: http://dx.doi.org/10.22377/ajp.v3i3.271

Refbacks

  • There are currently no refbacks.