Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
권호 표지
DOI QR코드

DOI QR Code

Dexamethasone Release from Glutaraldehyde Cross-Linked Chitosan Microspheres: In Vitro/In Vivo Studies and Non-Clinical Parameters Response in Rat Arthritic Model

  • Received : 2011.07.15
  • Accepted : 2011.10.08
  • Published : 2011.10.20
Download PDF
⟨ Previous Next ⟩

Abstract

The Dexamethasone (DEX) loaded chitosan microspheres were prepared by thermal denaturation and chemical cross-linking method using a dierent concentration of glutaraldehyde as chemical cross-linking agent. The prepared microspheres were evaluated for the percentage of Drug Loading (DL), Encapsulation Efficiency (EE) and surface morphology by Scanning Electron Microscopy (SEM). DL and EE were found to be maximum range of 10.0 to 10.79 % and 58.19 to 64.73 % respectively. The SEM Photographs of the resultant microspheres exhibited fairly smooth surfaces and predominantly spherical in appearance. In addition, Fourier Transform Infrared Spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) shown that there was no interaction between the drug and polymer. In vitro and in vivo release studies revealed that the release of dexamethasone was sustained and extended up to 63 days and effectively controlled by the extent of cross-linking agent. Non-clinical parameters such as paw volume, hematological parameters like Erythrocyte Sedimentation Rate (ESR), Paced Cell Volume (PCV), Total Leucocytes Count (TLC), Hemoglobin (Hb), Differential Cell Count (DCC) were investigated in Fruend's Complete Adjuvant (FCA) induced arthritic rats. Radiology and histopathological studies were also performed in order to evaluate the therapeutic efficacy of the DEX-loaded microspheres in extenuating the rat arthritic model.

Keywords

References

  1. Assen, S.V., Holvast, A., Benne, C.A., Posthumus, M.D., 2010. Humoral Responses After Influenza Vaccination Are Severely Reduced in Patients With Rheumatoid Arthritis Treated With Rituximab. Arthritis & Rheumatism. 62, 75-81. https://doi.org/10.1002/art.25033
  2. Beck, R.C.R., Pohlmann, A.R., Homeister, C., Gallas, M.R., Collnot, E., Schaefer, U.F., Guterres, S.S., Lehr, C.M., 2007. Dexamethasone- loaded nanoparticle-coated microparticles: Correlation between in-vitro drug release and drug transport across Caco-2 cell monolayers. Eur. J. Pharm. Biopharm. 67, 18-30. https://doi.org/10.1016/j.ejpb.2007.01.007
  3. Blanco, M.D., Gomez, C., Olmo, R., Muniz, E., Teijion, J.M., 2000. Chitosan microspheres in PLG films as devices for cytarabine release. Int. J. Pharm. 202, 29-39. https://doi.org/10.1016/S0378-5173(00)00408-7
  4. Celik, O., Akbuga, J., 2007. Preparation of superoxide dismutase loaded chitosan microspheres: characterization and release studies. E. J. Pharm. Biopharm. 66, 42-47. https://doi.org/10.1016/j.ejpb.2006.08.016
  5. Chaudhuri, K., Paul, A., 2008. Glucocorticoids and rheumatoid arthritis-a reappraisal. Ind J. Rheumatology. 3, 21-28. https://doi.org/10.1016/S0973-3698(10)60075-1
  6. Derendorf, H., Rohdewald, P., Hochhaus, G., Mollmann, H., 1986. HPLC determination of glucocorticoid alcohols, their phosphates and hydrocortisone in aqueous solutions and biological fluids. J. Pharm. Biomed. Anal. 4, 197-206. https://doi.org/10.1016/0731-7085(86)80042-5
  7. Dhanaraju, M.D., Vema, K., Jayakumar, R., Vamsadhara, C., 2003. Preparation and characterization of injectable microspheres of contraceptive hormones. Int. J. Pharm. 268, 23-29. https://doi.org/10.1016/j.ijpharm.2003.08.011
  8. Duarte, A.R.C., Mano, J.F., Reis, R.L., 2009. Preparation of chitosan scaffolds loaded with dexamethasone for tissue engineering applications using supercritical uid technology. European Polymer Journal. 45, 141-148. https://doi.org/10.1016/j.eurpolymj.2008.10.004
  9. Feng, S., Huang, G., 2001. Effects of emulsifiers on the controlled release of paclitaxel (Taxol) from nanospheres of biodegradable polymers. J. Control. Release. 71, 53-69. https://doi.org/10.1016/S0168-3659(00)00364-3
  10. Gibaly, E., 2002. Development and in vitro evaluation of novel floating chitosan microcapsules for oral use: comparison with non-floating chitosan microspheres. Int. J. Pharm. 249, 7-21. https://doi.org/10.1016/S0378-5173(02)00396-4
  11. Gupta, K.C., Jabrail, F.H., 2007. Glutaraldehyde cross-linked chitosan microspheres for controlled release of centchroman. Carbohydrate Res. 342, 2244-2252. https://doi.org/10.1016/j.carres.2007.06.009
  12. He, P., Davis, S.S., Illum, L., 1999. Chitosan microspheres prepared by spray drying. Int. J. Pharm. 187, 53-65. https://doi.org/10.1016/S0378-5173(99)00125-8
  13. Hu, F., Hepburn, H.R., Li, Y., Chen, M., Radloff, S.E., Daya, S., 2005. Effects of ethanol and water extracts of propolis (bee glue) on acute inflammatory animal models. J. Ethnopharmacol. 100, 276-83. https://doi.org/10.1016/j.jep.2005.02.044
  14. Iwanaga, K., Yabuta, T., Kakemi, M., Morimoto, K., Tabata, Y., Ikada, Y., 2003. Usefulness of microspheres composed of gelatin with various cross-linking density. J. Microencapsul. 20, 767-776. https://doi.org/10.3109/02652040309178087
  15. Jameela, S.R., Jayakrishnan, A., 1995. Glutaraldehyde cross-linked chitosan microspheres as a long acting biodegradable drug delivery vehicle: studies on the in vitro release of mitoxantrone and in vivo degradation of microspheres in rat muscle. Biomaterials. 16, 769-775. https://doi.org/10.1016/0142-9612(95)99639-4
  16. Jameela, S.R., Kumary, J.V., Lal, A.U., Jayakrishnan, H., 1998. Progesterone - loaded chitosan microspheres: a long acting biodegradable controlled delivery system. J. Control. Release. 52, 17-24. https://doi.org/10.1016/S0168-3659(97)00187-9
  17. Jameela, S.R., Misra, A., Jayakrishnan, A., 1994. Crosslinked chitosan microspheres as carriers for prolonged delivery of macromolecular drugs. J.Biomat. Sci. Polym. 6, 621-632.
  18. Jeffery, H., Davis, S.S., O'Hagan, D.T., 1991. The preparation and characterization of poly (lactide-co-glycolide) microparticles. I. Oil-in-water emulsion solvent evaporation. Int. J. Pharm. 77, 169-175. https://doi.org/10.1016/0378-5173(91)90314-E
  19. Kumar, D.A., Kalidindi, V.S., Raju, N., Settu, K., Kumanan, K., Puvanakrishnan, R., 2005. Effect of a derivatized tetrapeptide from lactoferrin on nitric oxide mediated matrix metalloproteinase- 2 production by synovial fibroblasts in collageninduced arthritis in rats. Peptides. 27, 1434-1442.
  20. Kumar, V.L., Roy, S., Sehgal, R., Padhy, B.M., 2006. A comparative study on the efficacy of rofecoxib in monoarticular arthritis induced by latex of Calotropis procera and Freund's Complete Adjuvant. Inflammopharmacology. 14, 17-21. https://doi.org/10.1007/s10787-006-1512-x
  21. Liu, Y.F., Huang, K.L., Peng, D.M., Ding, P., Li, G.Y., 2007. Preparation and characterization of glutaraldehyde cross-linked O carboxy methyl chitosan microspheres for controlled delivery of pazuoxacin mesilate. Int. J. Biol. Macromol. 41, 87-93. https://doi.org/10.1016/j.ijbiomac.2007.01.003
  22. Ofokansi, K.C., Adikwu, M.U., 2007. Formulation and evaluation of microspheres based on gelatin-mucin admixtures for the rectal delivery of cefuroxime sodium. Trop. J. Pharm. Res. 6, 825-832.
  23. Orienti, I., Cerchiara, T., Luppi, B., Bigucci, F., Zuccari, G., Zecchi, V., 2002. Infuence of diferent chitosan salts on the release of sodium diclofenac in colon specifc delivery. Int. J. Pharm. 238, 51-59. https://doi.org/10.1016/S0378-5173(02)00060-1
  24. Patil, K.R., Patil, C.R., Jadhav, R.B., Mahajan, V.K., Patil, P.R., Gaikwad, P.S., 2009 Anti-arthritic Activity of Bartogenic Acid Isolated from Fruits of Barringtonia racemosa Roxb (Lecythidaceae). Ecam. 1-7.
  25. Poovi, G., Dhanalekshmi, U.M., Narayanan, N., Neelakanta Reddy, P., 2011. Preparation and Characterization of Repaglinide Loaded Chitosan Polymeric Nanoparticles. Research J. Nanosci and Nanotech. 1, 12-24. https://doi.org/10.3923/rjnn.2011.12.24
  26. Ramachandran, S., Shaheedha, S.M., Thirumurugan, G., Dhanaraju, M.D., 2010. Floating controlled drug delivery system of famotidine loaded hollow microspheres (microballoons) in the stomach. Curr. Drug. Deliv. 1, 93-97.
  27. Ravi, S., Peh, K.K., Darwis, Y., Krishna Murthy, B., Raghu Raj Singh, T., Mallikarjun, C., 2008. Development and characterization of polymeric microspheres for controlled release protein loaded drug delivery system. Ind. J. Pharm. Sci. 70, 303-309. https://doi.org/10.4103/0250-474X.42978
  28. Sarika, A., Singh, V., Sherawat, R., Sharma, P., Yadav, S., Kumar, A., 2010. Assessment of antiarthritic and immunomdulatory properties of Lactobacillus casei in collagen induced arthritis (CIA) experimental model. Int. J. Integrat. Biol. 9, 142-148.
  29. Vieira, R.S., Beppu, M.M., 2006. Dynamic and static adsorption and desorption of Hg (II) ions on chitosan membranes and spheres. Water Res. 40, 1726-1734. https://doi.org/10.1016/j.watres.2006.02.027
  30. Vishal Gupta, N., Shivakumar, H.G., 2010. Preparation and characterization of superporous hydrogels as gastroretentive drug delivery system for rosiglitazone maleate, DARU. 18, 200-210.
  31. Wang, D., Miller, S.C., Liu, X.M., Anderson, B., Wang, X.S., Goldring, S.R., 2007. Novel dexamethasone-HPMA copolymer conjugate and its potential application in treatment of rheumatoid arthritis. Arthritis Research & Therapy. 9, R2. https://doi.org/10.1186/ar2106