Skip to main content
PMC home page
AAPS PharmSciTech logoLink to AAPS PharmSciTech
. 2005 Sep 20;6(1):E65–E73. doi: 10.1208/pt060112

Albumin microspheres as carriers for the antiarthritic drug celecoxib

Hetal Thakkar 1, Rakesh Kumar Sharma 1, Anil Kumar Mishra 2, Krishna Chuttani 2, Rayasa Ramchandra Murthy 1,✉
PMCID: PMC2750413  PMID: 16353965

Abstract

The present study investigates the preparation of celecoxib-loaded albumin microspheres and the biodistribution of technetium-99m (99mTc)-labeled celecoxib as well as its microspheres after intravenous administration. Microspheres were prepared using a natural polymer BSA using emulsification chemical cross-linking method. The prepared microspheres were characterized for entrapment efficiency, particle size, and in vitro drug release. Surface morphology was studied by scanning electron microscopy. Biodistribution studies were performed by radiolabeling celecoxib (CS) and its microspheres (CMS) using99mTc and injecting arthritic rats intravenously. The geometric mean diameter of the microspheres was found to be 5.46 μm. In vitro release studies indicated that the microspheres sustained the release of the drug for }6 days. Radioactivity measured in different organs after intravenous administration of celecoxib solution showed a significant amount of radioactivity in the liver and spleen. In case of celecoxib-loaded microspheres, a significant amount of radioactivity accumulated in the lungs. No significant difference (P>.1) in the radioactivity was observed between the inflamed joint and the noninflamed joint following intravenous injection of99mTc-CS. However, in case of the microspheres (CMS), the radioactivity present in the inflamed joint was 2.5-fold higher than in the noninflamed joint. The blood kinetic studies revealed that celecoxib-loaded albumin microspheres exhibited prolonged circulation than the celecoxib solution.

Keywords: microspheres, albumin, celecoxib, technetium-99m, biodistribution

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

References

  • 1.Bogdansky S. Natural polymers as drug delivery systems. In: Chasin M, Langer R, editors. Biodegradable Polymers as Drug Delivery Systems. New York, NY: Marcel Dekker Inc; 1990. pp. 231–259. [Google Scholar]
  • 2.Kramer PA. Albumin microspheres as vehicles for achieving specificity in drug delivery. J Pharm Sci. 1974;63:1646–1647. doi: 10.1002/jps.2600631044. [DOI] [PubMed] [Google Scholar]
  • 3.Bernard NG, Shaw SM, Kessler WV, Landolt RR, Peck GE, Dockerty GH. Distribution and degradation of I-125 albumin microspheres and technetium 99m sulphur colloid. J Pharm Sci. 1980;15:30–34. [Google Scholar]
  • 4.Schafer V, Briesen H, Rubsamen-Waigman H, Steffan AM, Royer C, Kreuter J. Phagocytosis and degradation of human serum albumin microspheres and nanoparticles in human macrophages. J Microencapsul. 1994;11:261–269. doi: 10.3109/02652049409040455. [DOI] [PubMed] [Google Scholar]
  • 5.Müller BG, Leuenberger H, Kissel T. Albumin nanospheres as carriers for passive drug targeting: an optimized manufacturing technique. Pharm Res. 1996;13:32–37. doi: 10.1023/A:1016064930502. [DOI] [PubMed] [Google Scholar]
  • 6.Tomilson E, Burger JJ, Schoolderwoerd EMA, McVie JG, Ilium JG. Human serum albumin microspheres for intra-arterial drug targeting of cytostatic compounds. In: Davis SS, editor. Microspheres and Drug Therapy. Amsterdam, The Netherlands: Elsevier; 1984. pp. 75–91. [Google Scholar]
  • 7.Tomilson E, Burger JJ. Monolithic albumin particles as drug carriers. In: Illum L, Davis SS, editors. Polymers in Controlled Drug Delivery. Bristol, UK: IOP Publishing Limited; 1987. pp. 25–48. [Google Scholar]
  • 8.Wunder A, Muller-Ladner U, Stelzer EH, et al. Albumin-based drug delivery as novel therapeutic approach for rheumatoid arthritis. J Immunol. 2003;170:4793–4801. doi: 10.4049/jimmunol.170.9.4793. [DOI] [PubMed] [Google Scholar]
  • 9.Breton J, Pezzi N, Molinari A, et al. Prolonged half-life in the circulation of a chemical conjugate between a pro-urokinase derivative and human serum albumin. Eur J Biochem. 1995;231:563–569. doi: 10.1111/j.1432-1033.1995.tb20733.x. [DOI] [PubMed] [Google Scholar]
  • 10.Srinath P, Chary MG, Vyas SP, Diwan PV. Long-circulating liposomes of indomethacin in arthritic rats: a biodisposition study. Pharm Acta Helv. 2000;74:399–404. doi: 10.1016/S0031-6865(00)00023-6. [DOI] [PubMed] [Google Scholar]
  • 11.Metselaar JM, Wauben MH, Wagenaar-Hilbers JP, Boerman OC, StorM G. Complete remission of experimental arthritis by joint targeting of glucocorticoids with long-circulating liposomes. Arthritis Rheum. 2003;48:2059–2066. doi: 10.1002/art.11140. [DOI] [PubMed] [Google Scholar]
  • 12.Corvo ML, Boerman OC, Oyen WJ, et al. Intravenous administration of superoxide dismutase entrapped in long circulating liposomes. II. In vivo fate in a rat model of adjuvant arthritis. Biochim Biophys Acta. 1999;1419:325–334. doi: 10.1016/S0005-2736(99)00081-4. [DOI] [PubMed] [Google Scholar]
  • 13.Perazella MA, Eras J. Are selective COX-2 inhibitors nephrotoxic? Am J Kidney Dis. 2000;35:937–940. doi: 10.1016/S0272-6386(00)70266-6. [DOI] [PubMed] [Google Scholar]
  • 14.Bing RJ. Cyclooxygenase-2 inhibitors: is there an association with coronary or renal events? Curr Atheroscler Rep. 2003;5:114–117. doi: 10.1007/s11883-003-0082-2. [DOI] [PubMed] [Google Scholar]
  • 15.Brater DC. Effects of nonsteroidal anti-inflammatory drugs on renal function: focus on cyclooxygenase-2-selective inhibition. Am J Med. 1999;107(6A):65S–70S. doi: 10.1016/S0002-9343(99)00369-1. [DOI] [PubMed] [Google Scholar]
  • 16.Tacconelli S, Capone ML, Patrignani P. Clinical pharmacology of novel selective COX-2 inhibitors. Curr Pharm Des. 2004;10:589–601. doi: 10.2174/1381612043453108. [DOI] [PubMed] [Google Scholar]
  • 17.Alper AB, Meleg-Smith S, Krane NK. Nephrotic syndrome and interstitial nephritis associated with celecoxib. Am J Kidney Dis. 2002;40:1086–1090. doi: 10.1053/ajkd.2002.36349. [DOI] [PubMed] [Google Scholar]
  • 18.Lewis DA, Field WN, Hayes K, Alpar HO. The use of albumin microspheres in the treatment of carageenan-induced inflammation in the rat. J Pharm Pharmacol. 1992;44:271–274. doi: 10.1111/j.2042-7158.1992.tb03600.x. [DOI] [PubMed] [Google Scholar]
  • 19.Alpar HO, Field WN, Hyde R, Lewis DA. The transport of microspheres from the gastrointestinal tract to inflammatory air pouches in the rat. J Pharm Pharmacol. 1989;41:194–196. doi: 10.1111/j.2042-7158.1989.tb06429.x. [DOI] [PubMed] [Google Scholar]
  • 20.Tuncay M, Calis S, Kas HS, Ercan MT, Peksoy L, Hincal A. Diclofenac sodium incorporated PLGA (50:50) microspheres: formulation considerations and in-vitro/in-vivo evaluation. Int J Pharm. 2000;195(1–2):179–188. doi: 10.1016/S0378-5173(99)00394-4. [DOI] [PubMed] [Google Scholar]
  • 21.Richardson VJ, Jeyashingh K, Jewkes RF. Properties of [99mTc] labeled liposomes in normal and tumor bearing rats. Biochem Soc Trans. 1977;5:290–291. doi: 10.1042/bst0050290. [DOI] [PubMed] [Google Scholar]
  • 22.Theobald AE. Quality Control of Radiopharmaceuticals. In: Sampson CB, editor. Textbook of Radiopharmacy: Theory and Practice. New York, NY: Gordon and Breach Science Publishers; 1990. pp. 127–129. [Google Scholar]
  • 23.Vogel GH, Vogel WH. Drug Discovery and Evaluation-Pharmacological Assays. Berlin, Germany: Springer Verlag; 1997. Anti-athoratic and immunomodulatory activity; pp. 421–460. [Google Scholar]
  • 24.Wu MS, Robbins JC, Bugianesi RL, Ponpipom MM, Shen TV. Modified in vivo behavior of liposomes containing synthetic glycolipids. Biochim Biophys Acta. 1981;674:19–29. doi: 10.1016/0304-4165(81)90342-1. [DOI] [PubMed] [Google Scholar]
  • 25.Sahin S, Selek H, Ponchel G, et al. Preparation, characterization and in vivo distribution of terbutaline sulfate loaded albumin microspheres. J Control Release. 2002;82:345–358. doi: 10.1016/S0168-3659(02)00141-4. [DOI] [PubMed] [Google Scholar]
  • 26.Jameela SR, Kumary TV, Lal AV, Jayakrishnan A. Progesterone loaded chitosan microspheres: a long acting biodegradable controlled delivery system. J Control Release. 1998;52:17–24. doi: 10.1016/S0168-3659(97)00187-9. [DOI] [PubMed] [Google Scholar]
  • 27.United States Pharmacopoeia XXII National Formulary XVII. Rockville, MD: United States Pharmacopeial Convention; 1990. Glutaral disinfectant solution; pp. 1934–1934. [Google Scholar]
  • 28.Wunderlich G, Pinkert J, Andreeff M, et al. Preparation and biodistribution of rhenium-188 labeled albumin microspheres: a promising new agent for radiotherapy. Appl Radiat Isot. 2000;52:63–68. doi: 10.1016/S0969-8043(99)00093-7. [DOI] [PubMed] [Google Scholar]
  • 29.Rhodes BA, Zölle I, Buchanan JW, Wagner HN. Radioactive albumin microspheres for studies of the pulmonary circulation. Radiology. 1969;92:1453–1460. doi: 10.1148/92.7.1453. [DOI] [PubMed] [Google Scholar]
  • 30.Lee TK, Sokoloski TD, Royer GP. Serum albumin beads: an injectable biodegradable system for the sustained release of drugs. Science. 1981;213(4504):233–235. doi: 10.1126/science.6787705. [DOI] [PubMed] [Google Scholar]
  • 31.Komaki R, Liao Z, Milas L. Improvement strategies for molecular targeting: cyclo-oxygenase-2 inhibitors as radiosensitizers for non-small cell lung cancer. Semin Oncol. 2004;31:47–53. doi: 10.1053/j.seminoncol.2003.12.014. [DOI] [PubMed] [Google Scholar]
  • 32.Cuzzocrea S, Mazzon E, Sautebin L, et al. Protective effects of celecoxib in lung injury and red blood cells modification induced by carageenan in the rat. Biochem Pharmacol. 2002;63:785–795. doi: 10.1016/S0006-2952(01)00908-X. [DOI] [PubMed] [Google Scholar]
  • 33.Cerchietti LC, Navigante AH, Peluffo GD, et al. Effects of celecoxib, medroxyprogesterone, and dietary intervention on systemic syndromes in patients with advanced lung adenocarcinoma: a pilot study. J Pain Symptom Manage. 2004;27:85–95. doi: 10.1016/j.jpainsymman.2003.05.010. [DOI] [PubMed] [Google Scholar]
  • 34.Diperna CA, Bart RD, Sievers EM, Ma Y, Starnes VA, Bremner RM. Cyclooxygenase-2 inhibition decreases primary and metastatic tumor burden in a murine model of orthotopic lung adenocarcinoma. J Thorac Cardiovasc Surg. 2003;126:1129–1133. doi: 10.1016/S0022-5223(03)00790-6. [DOI] [PubMed] [Google Scholar]
  • 35.Peluffo GD, Stillitani I, Rodriguez VA, Diament MJ, Klein SM. Reduction of tumor progression and paraneoplastic syndrome development in murine lung adenocarcinoma by nonsteroidal anti-inflammatory drugs. Int J Cancer. 2004;110:825–830. doi: 10.1002/ijc.20226. [DOI] [PubMed] [Google Scholar]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists

RESOURCES