FORMULATION AND CHARACTERIZATION OF NANO LIPID CARRIER DRY POWDER INHALER CONTAINING CIPROFLOXACIN HYDROCHLORIDE AND N-ACETYL CYSTEINE

RS R Murthy, Himanshi Khattar, Simranjit Singh

Abstract


ABSTRACT

Nanolipid carriers (NLC) are developed as an alternative to solid lipid nanocarriers in order to increase the payload and to prevent drug expulsion. In this study, NLCs loaded with ciprofloxacin hydrochloride (CIP) and N-Acetyl cysteine (NAC) were prepared and evaluated for its delivery to the lung for treatment of the symptoms of cystic fibrosis and chronic obstructive pulmonary disorder. NLCs prepared by emulsification and sonication technique using cetyl palmitate (the solid lipid, 2%) and oleic acid (as the liquid lipid, 2%) and Tween80 (surfactant, 0.25%) showed smaller particle sizes (of199.1 ±1.859 nm) and relatively high encapsulation efficiencies (72.143±1.8 %.) and optimum zeta potential (-38.27 ± 0.384 mV).A novel DPI formulations loaded with the NLC containing CIP(CIP-DPI), NAC (NAC-DPI) and CIP/NAC combination (CIP-NAC-DPI) were prepared by freeze drying method using Lactose (8%w/v) as a cryoprotectant. The DPI prepared showed good flow properties, prolonged drug release and improved stability. In-vitro drug release profile of CIP HCl in case of CIP-NLC showed 55 % release in 15 hours while it was 60% in case of CIP-NLC-DPI formulation. Similar is the case with NAC formulations. Following intratracheal administration in rat model, the percentage of CIP extracted from lungs was 70.2% in case on CIP-NAC-DPI against 49.8% for CIP-DPI and 42.1% for plain CIP. This amount is about 1.6 times increase in CIP in lungs by co-administration with NAC. However, no appreciable change in the residence time of CIP in lungs after intratracheal administration of CIP-DPI and combined DPI (CIP-NAC-DPI) was noted.

Keywords: Ciprofloxacin Hydrochloride, N-Acetyl Cysteine, Nano lipid Carriers, Dry powder inhaler, cystic fibrosis.

 


Keywords


Ciprofloxacin Hydrochloride, N-Acetyl Cysteine, Nano Lipid Carriers; Dry Powder Inhaler; Cystic Fibrosis

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References


.Courtney J M. M. Ennis, and J.S. Elborn, Cytokines and inflammatory mediators in cystic fibrosis. J Cyst Fibros, 2004. 3(4): p. 223-31.

Driscoll, J.A., S.L. Brody, and M.H. Kollef, The epidemiology, pathogenesis and treatment of Pseudomonas aeruginosa infections. Drugs, 2007. 67(3): p. 351-68.

.Pauwels, R.A. Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group. N Engl J Med, 1997. 337(20): p. 1405-11.

.Edsbacker, S. and C.J. Johansson, Airway selectivity: an update of pharmacokinetic factors affecting local and systemic disposition of inhaled steroids. Basic Clin Pharmacol Toxicol, 2006. 98(6): p. 523-36.

Abu-Dahab, R., U.F. Schafer, and C.M. Lehr, Lectin-functionalized liposomes for pulmonary drug delivery: effect of nebulization on stability and bioadhesion. Eur J Pharm Sci, 2001. 14(1): p. 37-46.

Bailey, M.M. and C.J. Berkland, Nanoparticle formulations in pulmonary drug delivery. Med Res Rev, 2009. 29(1): p. 196-212.

Chono, S., et al., Efficient drug delivery to lung epithelial lining fluid by aerosolization of ciprofloxacin incorporated into PEGylated liposomes for treatment of respiratory infections. Drug Dev Ind Pharm, 2011. 37(4): p. 367-72.

Pourshahab, P.S., et al., Preparation and characterization of spray dried inhalable powders containing chitosan nanoparticles for pulmonary delivery of isoniazid. J Microencapsul, 2011. 28(7): p. 605-13.

Jores, K., et al., Solid lipid nanoparticles (SLN) and oil-loaded SLN studied by spectrofluorometry and Raman spectroscopy. Pharm Res, 2005. 22(11): p. 1887-97.

Wong, J.P., et al., Liposome delivery of ciprofloxacin against intracellular Francisella tularensis infection. J Control Release, 2003. 92(3): p. 265-73.

Alovero, F.L., M.E. Olivera, and R.H. Manzo, In vitro pharmacodynamic properties of a fluoroquinolone pharmaceutical derivative: hydrochloride of ciprofloxacin-aluminium complex. Int J Antimicrob Agents, 2003. 21(5): p. 446-51.

Li, F.Q., et al., Ciprofloxacin-loaded bovine serum albumin microspheres: preparation and drug-release in vitro. J Microencapsul, 2001. 18(6): p. 825-9.

Finlay, W.H., Wong, J.P., , Regional lung deposition of nebulized liposome encapsulated ciprofloxacin. Int. J. Pharm, 1998(167): p. 121-127.

Hodson, M.E., et al., Dornase alfa in the treatment of cystic fibrosis in Europe: a report from the Epidemiologic Registry of Cystic Fibrosis. Pediatr Pulmonol, 2003. 36(5): p. 427-32.

Deterding, R., et al., Safety and tolerability of denufosol tetrasodium inhalation solution, a novel P2Y2 receptor agonist: results of a phase 1/phase 2 multicenter study in mild to moderate cystic fibrosis. Pediatr Pulmonol, 2005. 39(4): p. 339-48.

Jones, A.M. and J.M. Helm, Emerging treatments in cystic fibrosis. Drugs, 2009. 69(14): p. 1903-10.

Donaldson, S.H., et al., Mucus clearance and lung function in cystic fibrosis with hypertonic saline. N Engl J Med, 2006. 354(3): p. 241-50.

Serisier, D.J., et al., Inhaled heparin in cystic fibrosis. Eur Respir J, 2006. 27(2): p. 354-8.

Suk, J.S., et al., Rapid transport of muco-inert nanoparticles in cystic fibrosis sputum treated with N-acetyl cysteine. Nanomedicine (Lond), 2011. 6(2): p. 365-75.

Matsuyama, T., et al., Improved nasal absorption of salmon calcitonin by powdery formulation with N-acetyl-L-cysteine as a mucolytic agent. J Control Release, 2006. 115(2): p. 183-8.

Daviskas, E., et al., Inhalation of dry-powder mannitol increases mucociliary clearance. Eur Respir J, 1997. 10(11): p. 2449-54.

Suk, J.S., et al., N-acetylcysteine enhances cystic fibrosis sputum penetration and airway gene transfer by highly compacted DNA nanoparticles. Mol Ther, 2011. 19(11): p. 1981-9.

Parry, M.F. and H.C. Neu, Effect of N-acetylcysteine on antibiotic activity and bacterial growth in vitro. J Clin Microbiol, 1977. 5(1): p. 58-61.

Lawson, D. and B.A. Saggers, N.A.C. And Antibiotics in Cystic Fibrosis. Br Med J, 1965. 1(5430): p. 317.

Heaf, D.P., G.J. Webb, and D.J. Matthew, In vitro assessment of combined antibiotic and mucolytic treatment for Pseudomonas aeruginosa infection in cystic fibrosis. Arch Dis Child, 1983. 58(10): p. 824-6.

El-Feky, M.A., et al., Effect of ciprofloxacin and N-acetylcysteine on bacterial adherence and biofilm formation on ureteral stent surfaces. Pol J Microbiol, 2009. 58(3): p. 261-7.

Ozdil, B., et al., Potential benefits of combined N-acetylcysteine and ciprofloxacin therapy in partial biliary obstruction. J Clin Pharmacol, 2010. 50(12): p. 1414-9.

Yang, Y., et al., Mannitol-guided delivery of Ciprofloxacin in artificial cystic fibrosis mucus model. Biotechnol Bioeng, 2011. 108(6): p. 1441-9.

Chattopadhyay, N., et al., Solid lipid nanoparticles enhance the delivery of the HIV protease inhibitor, atazanavir, by a human brain endothelial cell line. Pharm Res, 2008. 25(10): p. 2262-71.

Joshi, M.R. and A. Misra, Liposomal budesonide for dry powder inhaler: preparation and stabilization. AAPS PharmSciTech, 2001. 2(4): p. 25.

Liu, D., et al., Nanostructured lipid carriers as novel carrier for parenteral delivery of docetaxel. Colloids Surf B Biointerfaces, 2011. 85(2): p. 262-9.

Jurima-Romet, M. and P.N. Shek, Lung Uptake of Liposome-entrapped Glutathione After Intratracheal Administration. Journal of Pharmacy and Pharmacology, 1991. 43(1): p. 6-10.

Joshi, M. and A. Misra, Disposition kinetics of ketotifen from liposomal dry powder for inhalation in rat lung. Clin Exp Pharmacol Physiol, 2003. 30(3): p. 153-6.

Webb, M.S., et al., Antibacterial efficacy against an in vivo Salmonella typhimurium infection model and pharmacokinetics of a liposomal ciprofloxacin formulation. Antimicrob Agents Chemother, 1998. 42(1): p. 45-52.

App, E.M., et al., Dose-finding and 24-h monitoring for efficacy and safety of aerosolized Nacystelyn in cystic fibrosis. Eur Respir J, 2002. 19(2): p. 294-302.


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