Effect of betamethasone phosphate loaded polymeric nanoparticles on a murine asthma model.

Although inhaled steroids are the treatment of first choice to control asthma, administration of systemic steroids is required for treatment of asthmatic exacerbation and intractable asthma. To improve efficacy and reduce side effects, we examine the effects of betamethasone disodium phosphate (BP) encapsulated in biocompatible, biodegradable blended nanoparticles (stealth nanosteroids) on a murine model of asthma. These stealth nanosteroids were found to accumulate at the site of airway inflammation and exhibit anti-inflammatory activity. Significant decreases in BALF eosinophil number were maintained for 7 days with a single injection of nanosteroids containing 40 microg BP. Airway responsiveness was also attenuated by the injection of stealth nanosteroids. A single injection of 40 microg of free BP and 8 microg of free BP once daily for 5 days did not show any significant effects. We conclude that stealth nanosteroids achieve prolonged and higher benefits at the site of airway inflammation compared to free steroids.

[1]  T. Ishihara,et al.  Treatment of experimental arthritis with poly(d, l-lactic/glycolic acid) nanoparticles encapsulating betamethasone sodium phosphate , 2005, Annals of the rheumatic diseases.

[2]  F M Muggia,et al.  ROLE OF COMPLEMENT ACTIVATION IN HYPERSENSITIVITY REACTIONS TO DOXIL AND HYNIC PEG LIPOSOMES: EXPERIMENTAL AND CLINICAL STUDIES , 2002, Journal of liposome research.

[3]  Y. Iwamoto,et al.  Dose Effects of Corticosteroids on the Development of Osteonecrosis in Rabbits , 2008, The Journal of Rheumatology.

[4]  R. Polosa,et al.  Immunomodulatory and biologic therapies for severe refractory asthma. , 2008, Respiratory medicine.

[5]  P. J. Barnes,et al.  Global strategy for asthma management and prevention: GINA executive summary , 2008, European Respiratory Journal.

[6]  K. Chung,et al.  Blood neutrophil activation markers in severe asthma: lack of inhibition by prednisolone therapy , 2006, Respiratory research.

[7]  D. Bazile,et al.  Stealth Me.PEG-PLA nanoparticles avoid uptake by the mononuclear phagocytes system. , 1995, Journal of pharmaceutical sciences.

[8]  Katsuaki Sato,et al.  Role of CCL21 and CCL19 in allergic inflammation in the ovalbumin-specific murine asthmatic model. , 2006, The Journal of allergy and clinical immunology.

[9]  Khusru Asadullah,et al.  Mechanisms involved in the side effects of glucocorticoids. , 2002, Pharmacology & therapeutics.

[10]  T. Kubota,et al.  Treatment of Experimental Arthritis with Stealth-Type Polymeric Nanoparticles Encapsulating Betamethasone Phosphate , 2009, Journal of Pharmacology and Experimental Therapeutics.

[11]  R. Goldman,et al.  Use of dexamethasone and prednisone in acute asthma exacerbations in pediatric patients. , 2009, Canadian family physician Medecin de famille canadien.

[12]  Treatment of experimental autoimmune uveoretinitis with poly(lactic acid) nanoparticles encapsulating betamethasone phosphate , 2006 .

[13]  M. Cazzola,et al.  Safety of inhaled corticosteroids: room for improvement. , 2007, Pulmonary pharmacology & therapeutics.

[14]  C. Bertrand,et al.  Time course of inflammatory and remodeling events in a murine model of asthma: effect of steroid treatment. , 2000, American journal of physiology. Lung cellular and molecular physiology.

[15]  J. Cidlowski,et al.  Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. , 2005, The New England journal of medicine.

[16]  S. Wise.  Nanocarriers as an emerging platform for cancer therapy , 2007 .

[17]  V. Turjanmaa,et al.  Possibilities of formoterol to enhance the peripheral lung deposition of the inhaled liposome corticosteroids. , 2002, Respiratory medicine.

[18]  S. Holgate.  Airway inflammation and remodeling in asthma: Current concepts , 2002, Molecular biotechnology.

[19]  S. Sanjar,et al.  Airway subepithelial fibrosis in a murine model of atopic asthma: suppression by dexamethasone or anti-interleukin-5 antibody. , 2000, American journal of respiratory cell and molecular biology.

[20]  P. Gangadharam,et al.  Efficacy of liposomal budesonide in experimental asthma. , 2003, The Journal of allergy and clinical immunology.

[21]  K. Avgoustakis,et al.  Pegylated poly(lactide) and poly(lactide-co-glycolide) nanoparticles: preparation, properties and possible applications in drug delivery. , 2004, Current drug delivery.

[22]  T. Ishihara,et al.  Efficient encapsulation of a water-soluble corticosteroid in biodegradable nanoparticles. , 2009, International journal of pharmaceutics.

[23]  J. Waldrep,et al.  Pulmonary delivery of beclomethasone liposome aerosol in volunteers. Tolerance and safety. , 1997, Chest.

[24]  T. Ishihara,et al.  Role of zinc in formulation of PLGA/PLA nanoparticles encapsulating betamethasone phosphate and its release profile. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[25]  P. Gangadharam,et al.  The use of sterically stabilized liposomes to treat asthma. , 2005, Methods in enzymology.

[26]  V. Turjanmaa,et al.  Regional lung deposition and clearance of 99mTc-labeled beclomethasone-DLPC liposomes in mild and severe asthma. , 1998, Chest.

[27]  R. Dahl.  Systemic side effects of inhaled corticosteroids in patients with asthma. , 2006, Respiratory medicine.

[28]  V. Torchilin,et al.  Biodegradable long-circulating polymeric nanospheres. , 1994, Science.

[29]  Ian M Adcock,et al.  New targets for drug development in asthma , 2008, The Lancet.

[30]  D. Mitchell,et al.  Attenuation of chronic pulmonary inflammation in A2B adenosine receptor knockout mice. , 2010, American journal of respiratory cell and molecular biology.

[31]  T C Yih,et al.  Engineered nanoparticles as precise drug delivery systems , 2006, Journal of cellular biochemistry.

[32]  S. Kawakami,et al.  PEGylated liposomes loading palmitoyl prednisolone for prolonged blood concentration of prednisolone. , 2006, Biological & pharmaceutical bulletin.