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Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Dextran Microparticulate Inhalable Dry Powder for the Treatment of Cystic Fibrosis and Mucopolysaccharidosis

Author(s): Neel R. Solanki, Deepa H. Patel* and Dipali R. Talele

Volume 17, Issue 3, 2020

Page: [218 - 228] Pages: 11

DOI: 10.2174/1567201817666200122160110

Price: $65

Abstract

Background: Cystic Fibrosis (CF) is a genetic disease which affects the patient’s lungs, pancreas, liver, kidney and intestine and lacks sulfatase enzyme, leading to mucopolysaccharidosis. Colistin sulfate acts by interacting with phospholipids of bacterial cell membranes. Sulfatase enzyme reduces the high levels of sulfated glycosaminoglycans and glycolipids by the hydrolysis of sulfate esters in lysosome.

Objective: The aim of the present investigation was to prepare and evaluate dextran microparticulate inhalable dry powder for the efficient targeting of colistin sulfate at affected area of lung without causing the side effects in the treatment of CF and mucopolysaccharidosis.

Methods: Microparticulate dry powder was prepared by the lyophilization method and evaluated for particle size, % yield, % drug content, solid state characterization, in-vitro lung deposition study, and in-vitro drug release study.

Results: Particle size, % yield and % drug content were found to be 4.03 ± 0.196 µm, 94.02 % and 99.45 ± 0.015% respectively. Bulk density, tapped density, hausner’s ratio, carr’s index and angle of repose of optimized batch were found to be 0.216 ± 0.025 g/cm3, 0.236 ± 0.035 g/cm3, 1.09 ± 0.026, 8.47 ± 0.025 % and 26.10 ± 0.029˚ respectively. A fine particle fraction, fine particle dose, mass median aerodynamic diameter, geometric standard deviation and emitted dose were found to be 66.78%, 16.45 mg, 4.89 µm, 1.32 and 246.33 mg respectively. The % CDR of optimized batch was found to be 96.12 ± 0.049 % at 24 h.

Conclusion: Based on the obtained results, we conclude that dextran microparticulate inhalable dry powder might be suitable carrier for the delivery of colistin sulfate and sulfatase in combination via pulmonary route for the treatment of cystic fibrosis and mucopolysaccharidosis.

Keywords: Cystic Fibrosis (CF), mucopolysaccharidosis, colistin sulfate, sulfatase, dry powder inhaler, pulmonary.

Graphical Abstract

[1]
Riordan, J.R.; Rommens, J.M.; Kerem, B.; Alon, N.; Rozmahel, R.; Grzelczak, Z.; Zielenski, J.; Lok, S.; Plavsic, N.; Chou, J.L. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science, 1989, 245(4922), 1066-1073.
[http://dx.doi.org/10.1126/science.2475911] [PMID: 2475911]
[2]
O’Sullivan, B.P.; Freedman, S.D. Cystic fibrosis. Lancet, 2009, 373(9678), 1891-1904.
[http://dx.doi.org/10.1016/S0140-6736(09)60327-5] [PMID: 19403164]
[3]
de Hostos, E.L.; Schilling, J.; Grossman, A.R. Structure and expression of the gene encoding the periplasmic arylsulfatase of Chlamydomonas reinhardtii. Mol. Gen. Genet., 1989, 218(2), 229-239.
[http://dx.doi.org/10.1007/BF00331273] [PMID: 2476654]
[4]
Mucopolysaccharidoses Fact Sheet, NINDS, NIH Publication 2017, 3, 5115.
[5]
Davis, S.D.; Iannetta, A.; Wedgwood, R.J. Activity of colistin against Pseudomonas aeruginosa: inhibition by calcium. J. Infect. Dis., 1971, 124(6), 610-612.
[http://dx.doi.org/10.1093/infdis/124.6.610] [PMID: 4331350]
[6]
Newton, B.A. The properties and mode of action of the polymyxins. Bacteriol. Rev., 1956, 20(1), 14-27.
[http://dx.doi.org/10.1128/MMBR.20.1.14-27.1956] [PMID: 13303920]
[7]
Schindler, M.; Osborn, M.J. Interaction of divalent cations and polymyxin B with lipopolysaccharide. Biochemistry, 1979, 18(20), 4425-4430.
[http://dx.doi.org/10.1021/bi00587a024] [PMID: 226126]
[8]
Falagas, M.E.; Grammatikos, A.P.; Michalopoulos, A. Potential of old-generation antibiotics to address current need for new antibiotics. Expert Rev. Anti Infect. Ther., 2008, 6(5), 593-600.
[http://dx.doi.org/10.1586/14787210.6.5.593] [PMID: 18847400]
[9]
Beringer, P. The clinical use of colistin in patients with cystic fibrosis. Curr. Opin. Pulm. Med., 2001, 7(6), 434-440.
[http://dx.doi.org/10.1097/00063198-200111000-00013] [PMID: 11706322]
[10]
Fellows, P.J. Food processing technology: principles and practice. 1st Ed. Elsevier, Woodhead Publishers, IL, USA , 2009; p. 928.
[http://dx.doi.org/10.1533/9781845696344]
[11]
Claus, S.; Weiler, C.; Schiewe, J.; Friess, W. Optimization of the fine particle fraction of a lyophilized lysozyme formulation for dry powder inhalation. Pharm. Res., 2013, 30(6), 1698-1713.
[http://dx.doi.org/10.1007/s11095-013-1015-6] [PMID: 23568518]
[12]
Hanafy, A.S.; Farid, R.M.; ElGamal, S.S. Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer’s disease management: preparation and detection in rat brain. Drug Dev. Ind. Pharm., 2015, 41(12), 2055-2068.
[http://dx.doi.org/10.3109/03639045.2015.1062897] [PMID: 26133084]
[13]
Saini, D.; Biris, A.S.; Srirama, P.K.; Mazumder, M.K. Particle size and charge distribution analysis of pharmaceutical aerosols generated by inhalers. Pharm. Dev. Technol., 2007, 12(1), 35-41.
[http://dx.doi.org/10.1080/10837450601166536] [PMID: 17484142]
[14]
Mutasim, E.M.; Wagiealla, S.S.; Ahmed, G.E.; Awadalla, M.M. Derivative spectrophotometric methods for the analysis and stability studies of colistin sulphate. J. Chem., 2015, 2015, 5.
[http://dx.doi.org/10.1155/2015/624316]
[15]
Saleem, I.; Donovan, M.J.; Smyth, H.D. Particle size analysis: From microparticles to nanosystems. Am. Pharmaceut. Rev., 2007, 10(1), 126-130.
[16]
Huang, Z.; Scicolone, J.V.; Han, X.; Davé, R.N. Improved blend and tablet properties of fine pharmaceutical powders via dry particle coating. Int. J. Pharm., 2015, 478(2), 447-455.
[http://dx.doi.org/10.1016/j.ijpharm.2014.11.068] [PMID: 25475016]
[17]
Sun, C.C. Quantifying effects of moisture content on flow properties of microcrystalline cellulose using a ring shear tester. Powder Technol., 2016, 289, 104-108.
[http://dx.doi.org/10.1016/j.powtec.2015.11.044]
[18]
Kumaresan, C.; Sathishkumar, K. Development of an inhaled sustained release dry powder formulation of salbutamol sulphate, an antiasthmatic drug. Indian J. Pharm. Sci., 2016, 78(1), 136-142.
[http://dx.doi.org/10.4103/0250-474X.180261] [PMID: 27168692]
[19]
Puthli, S.; Vavia, P.R. Stability studies of microparticulate system with piroxicam as model drug. AAPS PharmSciTech, 2009, 10(3), 872-880.
[http://dx.doi.org/10.1208/s12249-009-9280-8] [PMID: 19568938]
[20]
Saharan, P.; Bhatt, D.; Saharan, S.P.; Bahmani, K. To study the effect of polymer and surfactant concentration on characteristics of nanoparticle formulations. Scholars Res. Libr., 2015, 7(12), 365-371.
[21]
Teja, S.P.S.; Damodharan, N. 23 full factorial model for particle size optimization of methotrexate loaded chitosan nanocarriers: a Design of Experiments (DoE) approach. BioMed Res. Int., 2018, 20187834159
[http://dx.doi.org/10.1155/2018/7834159] [PMID: 30356374]
[22]
Abdul-Fattah, A.M.; Lechuga-Ballesteros, D.; Kalonia, D.S.; Pikal, M.J. The impact of drying method and formulation on the physical properties and stability of methionyl human growth hormone in the amorphous solid state. J. Pharm. Sci., 2008, 97(1), 163-184.
[http://dx.doi.org/10.1002/jps.21085] [PMID: 17722086]
[23]
Yang, F.; Liu, X.; Wang, W.; Liu, C.; Quan, L.; Liao, Y. The effects of surface morphology on the aerosol performance of spray-dried particles within HFA 134a based metered dose formulations. Asian J. Pharmaceut. Sci., 2015, 10(6), 513-519.
[24]
Labiris, N.R.; Dolovich, M.B. Pulmonary drug delivery. Part II: the role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications. Br. J. Clin. Pharmacol., 2003, 56(6), 600-612.
[http://dx.doi.org/10.1046/j.1365-2125.2003.01893.x] [PMID: 14616419]
[25]
El-Gendy, N.; Huang, S.; Selvam, P.; Soni, P.; Berkland, C. Development of budesonide nanocluster dry powder aerosols: formulation and stability. J. Pharm. Sci., 2012, 101(9), 3445-3455.
[http://dx.doi.org/10.1002/jps.23176] [PMID: 22619045]

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