To investigate the efficacy of local biodegradable composites of hydroxyapatite, plaster of Paris, and a binder of either alginate or chitosan impregnated with methotrexate on human mammary carcinoma cells.
Methods.
An in vitro analysis of drug dissolution and a cytotoxicity test on human mammary carcinoma cells were performed over one month. Physicochemical properties of each composite were investigated using scanning electron microscopy, X-ray diffractometry, and Fourier transform infrared spectroscopy.
Results.
Both composites with a binder of either alginate or chitosan could release methotrexate for over one month. The amount of methotrexate released depended on the amount of methotrexate loaded. The composite using alginate as a binder released a significantly greater amount of methotrexate than that using chitosan as a binder (p<0.05). The elution of both composites showed favourable cytotoxicity when the concentration was greater than 5 μg/ml.
Conclusion.
Methotrexate-impregnated hydroxyapatite composites appear to be effective local skeletal methotrexate delivery systems against human mammary carcinoma cells in an in vitro model.
DahnersLEFunderburkCH. Gentamicin-loaded plaster of Paris as a treatment of experimental osteomyelitis in rabbits. Clin Orthop Relat Res1987;219:278–82.
2.
MorganSMAl-ShamkhaniACallantDSchachtEWoodleyJFDuncanR. Alginates as drug carriers: Covalent attachment of alginates to therapeutic agents containing primary amine groups. Int J Pharm1995;122:121–8.
3.
ItokazuMSugiyamaTOhnoTWadaEKatagiriY. Development of porous apatite ceramic for local delivery of chemotherapeutic agents. J Biomed Mater Res1986;39:536–8.
4.
DeckerSWinkelmannWNiesBvan ValenF. Cytotoxic effect of methotrexate and its solvent on osteosarcoma cells in vitro. J Bone Joint Surg Br1999;81:545–51.
5.
GrecoFde PalmaLSpecchiaNJacobelliSGagginiC. Polymethylmethacrylate-antiblastic drug compounds: An in vitro study assessing the cytotoxic effect in cancer cell lines—a new method for local chemotherapy of bone metastasis. Orthopedics1992;15:189–94.
6.
HillnerBEIngleJNBerensonJRJanjanNAAlbainKSLiptonA. American Society of Clinical Oncology guideline on the role of bisphosphonates in breast cancer. American Society of Clinical Oncology Bisphosphonates Expert Panel. J Clin Oncol2000;18:1378–91.
7.
PelusoGPetilloORanieriMSantinMAmbrosioLCalabroD. Chitosan-mediated stimulation of macrophage function. Biomaterials1994;15:1215–20.
8.
SaridD. Scanning force microscopy with applications to electric, magnetic, and atomic forces. New York: Oxford University Press; 1991:181–2.
9.
UchidaAShintoYArakiNOnoK. Slow release of anticancer drugs from porous calcium hydroxyapatite ceramic. J Orthop Res1992;10:440–5.
10.
WangHMGalaskoCSCrankSOliverGWardCA. Methotrexate loaded acrylic cement in the management of skeletal metastases. Biomechanical, biological, and systemic effect. Clin Orthop Relat Res1995;312:173–86.
11.
BuranapanitkitBIngviyaNLimAGeaterAPrasongsubTKalnauwakulS. In vitro elution of gentamicin from locally implantable beads. J Musculoskelet Res2000;4:169–76.
12.
BuranapanitkitBOungbhoKIngviyaN. The efficacy of hydroxyapatite composite impregnated with amphotericin B. Clin Orthop Relat Res2005;437:236–41.
13.
BuranapanitkitBSriniltaVIngvigaNOungbhoKGeaterAOvatlarnpornC. The efficacy of a hydroxyapatite composite as a biodegradable antibiotic delivery system. Clin Orthop Relat Res2004;424:244–52.
14.
LebugleARodriguesABonneviallePVoigtJJCanalPRodriguezF. Study of implantable calcium phosphate systems for the slow release of methotrexate. Biomaterials2002;23:3517–22.
15.
JolivetJCowanKHCurtGAClendeninnNJChabnerBA. The pharmacology and clinical use of methotrexate. N Engl J Med1983;309:1094–104.
16.
RosaMAMaccauroGSgambatoAArditoRFalconeGDe SantisV. Acrylic cement added with antiblastics in the treatment of bone metastases. Ultrastructural and in vitro analysis. J Bone Joint Surg Br2003;85:712–6.
17.
SidquiMCollinPVitteCForestN. Osteoblast adherence and resorption activity of isolated osteoclasts on calcium sulphate hemihydrate. Biomaterials1995;16:1327–32.
18.
BlahaJDNelsonCLFrevertLFHenrySLSeligsonDEsterhaiJLJr. The use of septopal (polymethylmethacrylate beads with gentamicin) in the treatment of chronic osteomyelitis. Instr Course Lect1990;39:509–14.
19.
BuranapanitkitBWongsiriS. Home-made local antibiotic cement for chronic osteomyelitis caused by resistant organisms. J ASEAN Orthop Assoc2001;14:27–31.
20.
BuranapanitkitBWongsiriSIngviyaNGeaterALimAKalnauwakulS. In vitro elution characteristics of antibiotic cement on MRSA organism. J ASEAN Orthop Assoc2000;13:53–6.
21.
ShamkhaniAADuncanR. Synthesis, controlled release properties and antitumour activity of alginate-cis-aconityl-daunomycin conjugates. Int J Pharm1995;122:107–19.
22.
AdamsKCouchLCiernyGCalhounJMaderJT. In vitro and in vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin Orthop Relat Res1992;278:244–52.
23.
AiminCChunlinHJuliangBTinyinZZinchaoD. Antibiotic loaded chitosan bar. An in vitro, in vivo study of a possible treatment for osteomyelitis. Clin Orthop Relat Res1999;366:239–47.
24.
CalhounJHHenrySLAngerDMCobosJAMaderJT. The treatment of infected nonunions with gentamicin-polymethylmethacrylate antibiotic beads. Clin Orthop Relat Res1993;295:23–7.
25.
MiclauTDahnersLELindseyRW. In vitro pharmacokinetics of antibiotic release from locally implantable materials. J Orthop Res1993;11:627–32.
26.
ShintoYUchidaAKorkusuzFArakiNOnoK. Calcium hydroxyapatite ceramic used as a delivery system for antibiotics. J Bone Joint Surg Br1992;74:600–4.
27.
WangXMaJFengQCuiF. Skeletal repair in rabbits with calcium phosphate cements incorporated phosphorylated chitin. Biomaterials2002;23:4591–600.
28.
NesbitMKrivitWHeynRSharpH. Acute and chronic effects of methotrexate on hepatic, pulmonary and skeletal systems. Cancer1976;37(2 Suppl):S1048–57.
29.
OriveGPonceSHernandezRMGasconARIgartuaMPedrazJL. Biocompatibility of microcapsules for cell immobilization elaborated with different type of alginates. Biomaterials2002;23:3825–31.
30.
CalhounJHMaderJT. Treatment of osteomyelitis with a biodegradable antibiotic implant. Clin Orthop Relat Res1997;341:206–14.
31.
JainAKPanchagnulaR. Skeletal drug delivery systems. Int J Pharm2000;206:1–12.
32.
HernigouPThieryJPBenoitJVoisinMCLerouxPHagegeG. Methotrexate diffusion from acrylic cement. Local chemotherapy for bone tumours. J Bone Joint Surg Br1989;71:804–11.
