Drug Release from PLGA Microspheres Attached to Solids Using Supercritical CO2

Abstract

Functionalization of a porous orthopedic implant with dexamethasone, a widely used anti-inflammatory drug, encapsulated within a biodegradable polymer for controlled release could help reduce or eliminate the inflammation response by the local tissue. In this research, we investigated the possibility of using supercritical carbon dioxide (CO₂) for attaching dexamethasone-loaded PLGA (polylactic-co-glycolic acid) microspheres to porous CoCrMo alloy for continuous delivery of dexamethasone. Supercritical CO₂ has been shown to be effective for attachment of PLGA microspheres to glass plates and porous CoCrMo alloy. Attached microspheres showed similar dexamethasone release profiles but different magnitude of burst release. Microspheres attached to the porous alloy samples using supercritical CO₂ at 10 bar and 40°C for 30 min showed a release profile similar to that of the nonattached microspheres. The microsphere morphology and the release profiles of microspheres attached to the glass plates and to the porous alloy samples suggest that dexamethasone burst release is enhanced by PLGA swelling at higher CO₂ pressures and better dispersion of microspheres. This study shows that microspheres can be incorporated into porous solids using supercritical CO₂, allowing for a wide variety of drug-biodegradable polymer formulations prepared using the proven emulsion/solvent evaporation method to be tested.

Keywords

microspheres PLGA supercritical CO2 dexamethasone drug delivery system continuous release orthopedic implant.

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References

Sun, Z.L. , Wataha, J.C. and Hanks, C.T. Effects of Metal Ions on Osteoblast-Like Cell Metabolism and Differentiation, J. Biomed. Mater. Res. , 1997: 34: 29-37.

Shettlemore, M.G. and Bundy, K.J. Toxicity Measurement of Orthopedic Implant Alloy Degradation Products Using a Bioluminescent Bacterial Assay , J. Biomed. Mater. Res., 1999: 45: 395-403.

Baldwin, L. and Hunt, J.A. Host Inflammatory Response to NiCr, CoCr, and Ti in a Soft Tissue Implantation Model, J. Biomed. Mater. Res. Part A, 2006 : 79: 574-581.

Kraft, C.N. , Burian, B. , Diedrich, O. , et al. Microvascular Response of Striated Muscle to Common Arthroplasty-Alloys: A Comparative In Vivo Study with CoCrMo, Ti-6Al-4V, and Ti-6Al-7Nb, J. Biomed. Mater. Res. Part A , 2005: 75: 31-40.

Ignatius, A.A. and Claes, L.E. In Vitro Biocompatibility of Bioresorbable Polymers: Poly(L, DL-lactide) and Poly(L-lactide-co-glycolide) , Biomat., 1996: 17: 831-839.

Anderson, J.M. and Shive, M.S. Biodegradation and Biocompatibility of PLA and PLGA Microspheres, Adv. Drug Deliv. Rev., 1997: 28: 5-24.

Wu, X.S. and Wang, N. Synthesis, Characterization, Biodegradation, and Drug Delivery Application of Biodegradable Lactic/Glycolic Acid Polymers. Part II: Biodegradation, J. Biomater. Sci., Polymer Edn , 2001: 12: 21-34.

Kim, D.-H. and Martin, D.C. Sustained Release of Dexamethasone from Hydrophilic Matrices Using PLGA Nanoparticles for Neural Drug Delivery , Biomater., 2006: 27: 3031-3037.

Galeska, I. , Kim, T.-K. , Patil, S.D. , et al. Controlled Release of Dexamethasone from PLGA Microspheres Embedded Within Polyacid-Containing PVA Hydrogels, AAPS J., 2005: 7: E231-E240.

10.

Gómez-Gaete, C. , Tsapis, N. , Besnard , M. , Bochot, A. and Fattal, E. Encapsulation of Dexamethasone into Biodegradable Polymeric Nanoparticles, Int. J. Pharm., 2007 : 331: 153-159.

11.

Zweers, M.L.T. , Engbers, G.H.M. , Grijpma, D.W. and Feijen, J. Release of Anti-restenosis Drugs from Poly(ethylene oxide)-Poly(DL-lactic-co-glycolic acid) Nanoparticles, J. Controll. Release, 2006: 114: 317-324.

12.

Kim, H. , Suh, H. , Jo , S.A. , et al. In Vivo Bone Formation by Human Marrow Stromal Cells in Biodegradable Scaffolds that Release Dexamethasone and Ascorbate-2-phosphate, Biochem. Biophys. Res. Commun. , 2005: 332: 1053-1060.

13.

Tsung, M.J. and Burgess, D.J. Preparation and Characterization of Gelatin Surface Modified PLGA Microspheres, AAPS PharmSci. , 2001: 3: Article 11.

14.

Hickey, T. , Kreutzer, D. , Burgess, D.J. and Moussy, F. In Vivo Evaluation of a Dexamethasone/PLGA Microsphere System Designed to Suppress the Inflammatory Tissue Response to Implantable Medical Devices , J. Biomed. Mater. Res., 2002: 61: 180-187.

15.

Hickey, T. , Kreutzer, D. , Burgess, D.J. and Moussy, F. Dexamethasone/ PLGA Microspheres for Continuous Delivery of an Anti-Inflammatory Drug for Implantable Medical Devices, Biomater., 2002: 23: 1649-1656.

16.

Patil, S.D. , Papadmitrakopoulos , F. and Burgess, D.J. Concurrent Delivery of Dexamethasone and VEGF for Localized Inflammation Control and Angiogenesis, J. Controll. Release, 2007: 117: 68-79.

17.

Kallinteri, P. , Antimisiaris , S.G. , Karnabatidis , D. , et al. Dexamethasone Incorporating Liposomes: An In Vitro Study of Their Applicability as a Slow Releasing Delivery System of Dexamethasone from Covered Metallic Stents, Biomater., 2002: 23: 4819-4826.

18.

Zilberman, M. , Shifrovitch, Y. , Aviv , M. and Hershkovitz , M. Structured Drug-eluting Bioresorbable Films: Microstructure and Release Profile, J. Biomater. Appl., 2009: 23: 385-406.

19.

Pan, Ch.J. , Tang, J.J. , Weng, Y.J. , Wang, J. and Huang, N. Preparation, Characterization and Anticoagulation of Curcumin-Eluting Controlled Biodegradable Coating Stents, J. Controll. Release, 2006 : 116: 42-49.

20.

Koegler, W.S. , Patrick, C. , Cima , M.J. and Griffith, L.G. Carbon Dioxide Extraction of Residual Chloroform from Biodegradable Polymers, J. Biomed. Mater. Res., 2002: 63: 567-576.

21.

Palakodaty, S. and York, P. Phase Behavioral Effects on Particle Formation Processes Using Supercritical Fluids, Pharm. Res. , 1999: 16: 976-985.

22.

Mooney, D.J. , Baldwin, D.F. , Suh, N.P. , Vacanti, J.P. and Langer, R. Novel Approach to Fabricate Porous Sponges of Poly(D,L-lactic-co-glycolic acid) Without the Use of Organic Solvents, Biomater., 1996: 17: 1417-1422.

23.

Yang, Y. , Zeng, C. and Lee, L.J. Three-Dimensional Assembly of Polymer Microstructures at Low Temperatures , Adv. Mater., 2004: 16: 560-564.

24.

Herberger, J. , Murphy, K. , Munyakazi , L. , Cordia, J. and Westhaus, E. Carbon Dioxide Extraction of Residual Solvents in Poly(lactide-co-glycolide) Microparticles , J. Controll. Release, 2003: 90: 181-195.

25.

Dawes, G.J.S. , Fratila-Apachitei , L.E. , Mulia, K. , et al. Size Effect of PLGA Spheres on Drug Loading Efficiency and Release Profiles, J. Mater. Sci.: Mater. Med., 2009: 20: 1089-1094.

26.

Liu, D. and Tomasko, D.L. Carbon Dioxide Sorption and Dilation of Poly(lactide-co-glycolide), J. Supercrit. Fluids , 2007: 39: 416-425.