Login Register Cart 0
Generic placeholder image

Current Drug Delivery

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Development and Optimization of Inhalable Levofloxacin Nanoparticles for The Treatment of Tuberculosis

Author(s): Sunny Shah*, Rohit Ghetiya, Moinuddin Soniwala and Jayant Chavda

Volume 18, Issue 6, 2021

Published on: 03 November, 2020

Page: [779 - 793] Pages: 15

DOI: 10.2174/1567201817999201103194626

Price: $65

Abstract

Background: Levofloxacin has been recommended by the WHO for the treatment of pulmonary tuberculosis and inhalable delivery of levofloxacin can be advantageous over conventional delivery.

Objective: This study aimed to develop and optimize inhalable levofloxacin Loaded Chitosan Nanoparticles (LCN). The objective was to achieve the mean particle size of LCN less than 300nm, sustain the drug release up to 24 h, and achieve MMAD of LCN of less than 5μm.

Methods: LCN were prepared by ionic gelation of chitosan with sodium tripolyphosphate (STPP) and subsequent lyophilization. A Plackett Burman screening design, 32 full factorial design, and overlay plots were sequentially employed to optimize the formulation. The mean particle size, % entrapment efficiency, in vitro drug release, and minimum inhibitory concentration were all evaluated.

Results: The Pareto chart from the Placket Burman screening design revealed that the concentrations of chitosan and STPP was found to be significant (p < 0.05). Further analysis by 32 full factorial design revealed that F-ratio for each model generated was found to be greater than the theoretical value (p < 0.05), confirming the significance of each model.

Conclusion: The optimized formulation showed a mean particle size of 171.5 nm, sustained the drug release up to 24 h in simulated lung fluid, and revealed MMAD of 3.18 μm, which can confirm delivery of the drug to the deep lung region. However, further in vivo studies are required to design a suitable dosage regimen and establish the fate of nanoparticles for safe and efficacious delivery of the drug.

Keywords: Levofloxacin, chitosan nanoparticles, pulmonary delivery, plackett burman screening design, minimum inhibitory concentration, optimization.

« Previous Next »
Graphical Abstract

[1]
World Health Organisation. Global Health Tuberculosis Report, 2019.
[2]
Cunha, L.; Rodrigues, S.; Rosa da Costa, A.M.; Faleiro, L.; Buttini, F.; Grenha, A. Inhalable chitosan microparticles for simultaneous delivery of isoniazid and rifabutin in lung tuberculosis treatment. Drug Dev. Ind. Pharm., 2019, 45(8), 1313-1320.
[http://dx.doi.org/10.1080/03639045.2019.1608231] [PMID: 30990096]
[3]
World Health Organisation. Global Health Tuberculosis Report, 2018.
[4]
Kendall, E.A.; Shrestha, S.; Cohen, T.; Nuermberger, E.; Dooley, K.E.; Gonzalez-Angulo, L.; Churchyard, G.J.; Nahid, P.; Rich, M.L.; Bansbach, C.; Forissier, T.; Lienhardt, C.; Dowdy, D.W. Priority-setting for novel drug regimens to treat tuberculosis: An epidemiologic model. PLoS Med., 2017, 14(1), e1002202.
[http://dx.doi.org/10.1371/journal.pmed.1002202] [PMID: 28045934]
[5]
Lee, S.F.K.; Laughon, B.E.; McHugh, T.D.; Lipman, M. New drugs to treat difficult tuberculous and nontuberculous mycobacterial pulmonary disease. Curr. Opin. Pulm. Med., 2019, 25(3), 271-280.
[http://dx.doi.org/10.1097/MCP.0000000000000570] [PMID: 30865034]
[6]
Pym, A.S.; Diacon, A.H.; Tang, S-J.; Conradie, F.; Danilovits, M.; Chuchottaworn, C.; Vasilyeva, I.; Andries, K.; Bakare, N.; De Marez, T.; Haxaire-Theeuwes, M.; Lounis, N.; Meyvisch, P.; Van Baelen, B.; van Heeswijk, R.P.G.; Dannemann, B. TMC207-C209 Study Group. Bedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis. Eur. Respir. J., 2016, 47(2), 564-574.
[http://dx.doi.org/10.1183/13993003.00724-2015] [PMID: 26647431]
[7]
Skripconoka, V.; Danilovits, M.; Pehme, L.; Tomson, T.; Skenders, G.; Kummik, T.; Cirule, A.; Leimane, V.; Kurve, A.; Levina, K.; Geiter, L.J.; Manissero, D.; Wells, C.D. Delamanid improves outcomes and reduces mortality in multidrug-resistant tuberculosis. Eur. Respir. J., 2013, 41(6), 1393-1400.
[http://dx.doi.org/10.1183/09031936.00125812] [PMID: 23018916]
[8]
Furin, J.; Cox, H.; Pai, M. Tuberculosis. Lancet, 2019, 393(10181), 1642-1656.
[http://dx.doi.org/10.1016/S0140-6736(19)30308-3] [PMID: 30904262]
[9]
Fox, G.J.; Nguyen, C.B.; Nguyen, T.A.; Tran, P.T.; Marais, B.J.; Graham, S.M.; Nguyen, B.H.; Velen, K.; Dowdy, D.W.; Mason, P.; Britton, W.J.; Behr, M.A.; Benedetti, A.; Menzies, D.; Nguyen, V.N.; Marks, G.B. Levofloxacin versus placebo for the treatment of latent tuberculosis among contacts of patients with multidrug-resistant tuberculosis (the VQUIN MDR trial): A protocol for a randomised controlled trial. BMJ Open, 2020, 10(1), e033945.
[http://dx.doi.org/10.1136/bmjopen-2019-033945] [PMID: 31900274]
[10]
Pharmaceutical, J. Clinical Trial, Available from: https://clinicaltrials.gov/ct2/show/NCT02365623
[11]
Churchyard, G.J.; Swindells, S. Controlling latent TB tuberculosis infection in high-burden countries: A neglected strategy to end TB. PLoS Med., 2019, 16(4), e1002787.
[http://dx.doi.org/10.1371/journal.pmed.1002787] [PMID: 31013273]
[12]
Bouton, T.C.; Phillips, P.P.J.; Mitnick, C.D.; Peloquin, C.A.; Eisenach, K.; Patientia, R.F.; Lecca, L.; Gotuzzo, E.; Gandhi, N.R.; Butler, D.; Diacon, A.H.; Martel, B.; Santillan, J.; Hunt, K.R.; Vargas, D.; von Groote-Bidlingmaier, F.; Seas, C.; Dianis, N.; Moreno-Martinez, A.; Horsburgh, C.R., Jr. An optimized background regimen design to evaluate the contribution of levofloxacin to multidrug-resistant tuberculosis treatment regimens: Study protocol for a randomized controlled trial. Trials, 2017, 18(1), 563.
[http://dx.doi.org/10.1186/s13063-017-2292-x] [PMID: 29178937]
[13]
Rau, J.L. The inhalation of drugs: Advantages and problems. Respir. Care, 2005, 50(3), 367-382.
[PMID: 15737247]
[14]
Dal Negro, R.W. Dry powder inhalers and the right things to remember: A concept review. Multidiscip. Respir. Med., 2015, 10(1), 13.
[http://dx.doi.org/10.1186/s40248-015-0012-5] [PMID: 25878791]
[15]
Tonnis, W.F.; Lexmond, A.J.; Frijlink, H.W.; de Boer, A.H.; Hinrichs, W.L. Devices and formulations for pulmonary vaccination. Expert Opin. Drug Deliv., 2013, 10(10), 1383-1397.
[http://dx.doi.org/10.1517/17425247.2013.810622] [PMID: 23786408]
[16]
Dharmadhikari, A.S.; Kabadi, M.; Gerety, B.; Hickey, A.J.; Fourie, P.B.; Nardell, E.; Phase, I. Phase I, single-dose, dose-escalating study of inhaled dry powder capreomycin: A new approach to therapy of drug-resistant tuberculosis. Antimicrob. Agents Chemother., 2013, 57(6), 2613-2619.
[http://dx.doi.org/10.1128/AAC.02346-12] [PMID: 23529740]
[17]
Chan, J.G.Y.; Tyne, A.S.; Pang, A.; McLachlan, A.J.; Perera, V.; Chan, J.C.Y.; Britton, W.J.; Chan, H.K.; Duke, C.C.; Young, P.M.; Traini, D. Murine pharmacokinetics of rifapentine delivered as an inhalable dry powder. Int. J. Antimicrob. Agents, 2015, 45(3), 319-323.
[http://dx.doi.org/10.1016/j.ijantimicag.2014.11.009] [PMID: 25554469]
[18]
Hirota, K.; Hasegawa, T.; Nakajima, T.; Makino, K.; Terada, H. Phagostimulatory effect of uptake of PLGA microspheres loaded with rifampicin on alveolar macrophages. Colloids Surf. B Biointerfaces, 2011, 87(2), 293-298.
[http://dx.doi.org/10.1016/j.colsurfb.2011.05.032] [PMID: 21700434]
[19]
Lawlor, C.; Kelly, C.; O’Leary, S.; O’Sullivan, M.P.; Gallagher, P.J.; Keane, J.; Cryan, S.A. Cellular targeting and trafficking of drug delivery systems for the prevention and treatment of MTb. Tuberculosis (Edinb.), 2011, 91(1), 93-97.
[http://dx.doi.org/10.1016/j.tube.2010.12.001] [PMID: 21237714]
[20]
Yadav, A.B.; Muttil, P.; Singh, A.K.; Verma, R.K.; Mohan, M.; Agrawal, A.K.; Verma, A.S.; Sinha, S.K.; Misra, A. Microparticles induce variable levels of activation in macrophages infected with Mycobacterium tuberculosis. Tuberculosis (Edinb.), 2010, 90(3), 188-196.
[http://dx.doi.org/10.1016/j.tube.2010.03.001] [PMID: 20382085]
[21]
Parumasivam, T.; Chang, R.Y.K.; Abdelghany, S.; Ye, T.T.; Britton, W.J.; Chan, H.K. Dry powder inhalable formulations for anti- tubercular therapy. Adv. Drug Deliv. Rev., 2016, 102, 83-101.
[http://dx.doi.org/10.1016/j.addr.2016.05.011] [PMID: 27212477]
[22]
Al Ayoub, Y.; Gopalan, R.C.; Najafzadeh, M.; Mohammad, M.A.; Anderson, D.; Paradkar, A.; Assi, K.H. Development and evaluation of nanoemulsion and microsuspension formulations of curcuminoids for lung delivery with a novel approach to understanding the aerosol performance of nanoparticles. Int. J. Pharm., 2019, 557, 254-263.
[http://dx.doi.org/10.1016/j.ijpharm.2018.12.042] [PMID: 30597263]
[23]
Costa, A.; Pinheiro, M.; Magalhães, J.; Ribeiro, R.; Seabra, V.; Reis, S.; Sarmento, B. The formulation of nanomedicines for treating tuberculosis. Adv. Drug Deliv. Rev., 2016, 102, 102-115.
[http://dx.doi.org/10.1016/j.addr.2016.04.012] [PMID: 27108703]
[24]
Mehta, P.; Bothiraja, C.; Kadam, S.; Pawar, A. Potential of dry powder inhalers for tuberculosis therapy: Facts, fidelity and future. Artif. Cells, Nanomedicine, Biotechnol., 2018, 46(3), S791-S806.
[25]
Safdar, R.; Omar, A.A.; Arunagiri, A.; Regupathi, I.; Thanabalan, M. Potential of chitosan and its derivatives for controlled drug release applications – A review. J. Drug Deliv. Sci. Technol., 2019, 49, 642-659.
[http://dx.doi.org/10.1016/j.jddst.2018.10.020]
[26]
Grenha, A.; Al-Qadi, S.; Seijo, B.; Remuñán-López, C. The potential of chitosan for pulmonary drug delivery. J. Drug Deliv. Sci. Technol., 2010, 20(1), 33-43.
[http://dx.doi.org/10.1016/S1773-2247(10)50004-2]
[27]
Rawal, T.; Parmar, R.; Tyagi, R.K.; Butani, S. Rifampicin loaded chitosan nanoparticle dry powder presents an improved therapeutic approach for alveolar tuberculosis. Colloids Surf. B Biointerfaces, 2017, 154, 321-330.
[http://dx.doi.org/10.1016/j.colsurfb.2017.03.044] [PMID: 28363192]
[28]
Gaspar, M.C.; Grégoire, N.; Sousa, J.J.S.; Pais, A.A.C.C.; Lamarche, I.; Gobin, P.; Olivier, J-C.; Marchand, S.; Couet, W. Pulmonary pharmacokinetics of levofloxacin in rats after aerosolization of immediate-release chitosan or sustained-release PLGA microspheres. Eur. J. Pharm. Sci., 2016, 93, 184-191.
[http://dx.doi.org/10.1016/j.ejps.2016.08.024] [PMID: 27531420]
[29]
Pai, R.V.; Jain, R.R.; Bannalikar, A.S.; Menon, M.D. Development and evaluation of chitosan microparticles based dry powder inhalation formulations of rifampicin and rifabutin. J. Aerosol Med. Pulm. Drug Deliv., 2016, 29(2), 179-195.
[http://dx.doi.org/10.1089/jamp.2014.1187] [PMID: 26406162]
[30]
Goyal, A.K.; Garg, T.; Rath, G.; Gupta, U.D.; Gupta, P. Development and characterization of nanoembedded microparticles for pulmonary delivery of antitubercular drugs against experimental tuberculosis. Mol. Pharm., 2015, 12(11), 3839-3850.
[http://dx.doi.org/10.1021/acs.molpharmaceut.5b00016] [PMID: 26436948]
[31]
Garg, T.; Rath, G.; Goyal, A.K. Inhalable chitosan nanoparticles as antitubercular drug carriers for an effective treatment of tuberculosis. Artif. Cells Nanomed. Biotechnol., 2016, 44(3), 997-1001.
[http://dx.doi.org/10.3109/21691401.2015.1008508] [PMID: 25682840]
[32]
Grenha, A.; Remuñán-López, C.; Carvalho, E.L.S.; Seijo, B. Microspheres containing lipid/chitosan nanoparticles complexes for pulmonary delivery of therapeutic proteins. Eur. J. Pharm. Biopharm., 2008, 69(1), 83-93.
[http://dx.doi.org/10.1016/j.ejpb.2007.10.017] [PMID: 18166446]
[33]
Rawal, T.; Kremer, L.; Halloum, I.; Butani, S. Dry-powder inhaler formulation of rifampicin: An improved targeted delivery system for alveolar tuberculosis. J. Aerosol Med. Pulm. Drug Deliv., 2017, 30(6), 388-398.
[http://dx.doi.org/10.1089/jamp.2017.1379] [PMID: 28510480]
[34]
Kumar, G.; Sharma, S.; Shafiq, N.; Khuller, G.K.; Malhotra, S. Optimization, in vitro-in vivo evaluation, and short-term tolerability of novel levofloxacin-loaded PLGA nanoparticle formulation. J. Pharm. Sci., 2012, 101(6), 2165-2176.
[http://dx.doi.org/10.1002/jps.23087] [PMID: 22392918]
[35]
Shah, S.R.; Prajapati, H.R.; Sheth, D.B.; Gondaliya, E.M.; Vyas, A.J.; Soniwala, M.M.; Chavda, J.R. Pharmacokinetics and in vivo distribution of optimized PLGA nanoparticles for pulmonary delivery of levofloxacin. J. Pharm. Pharmacol., 2020, 72(8), 1026-1037.
[http://dx.doi.org/10.1111/jphp.13275] [PMID: 32337714]
[36]
Rwegasila, E.; Mubofu, E.B.; Nyandoro, S.S.; Erasto, P.; Munissi, J.J.E. Preparation, characterization and in vivo antimycobacterial studies of panchovillin-chitosan nanocomposites. Int. J. Mol. Sci., 2016, 17(10), E1559.
[http://dx.doi.org/10.3390/ijms17101559] [PMID: 27689997]
[37]
Saeed, R.M.; Dmour, I.; Taha, M.O. Stable chitosan-based nanoparticles using polyphosphoric acid or hexametaphosphate for tandem ionotropic/covalent crosslinking and subsequent investigation as novel vehicles for drug delivery. Front. Bioeng. Biotechnol., 2020, 8, 4.
[http://dx.doi.org/10.3389/fbioe.2020.00004] [PMID: 32039190]
[38]
Shah, S.R.; Parikh, R.H.; Chavda, J.R.; Sheth, N.R. Application of Plackett–Burman screening design for preparing glibenclamide nanoparticles for dissolution enhancement. Powder Technol., 2013, 235, 405-411.
[http://dx.doi.org/10.1016/j.powtec.2012.10.055]
[39]
Shah, S.R.; Parikh, R.H.; Chavda, J.R.; Sheth, N.R. Glibenclamide nanocrystals for bioavailability enhancement: Formulation design, process optimization, and pharmacodynamic evaluation. J. Pharm. Innov., 2014, 9(3), 227-237.
[http://dx.doi.org/10.1007/s12247-014-9189-y]
[40]
Liu, Y.; Chen, Z.Q.; Zhang, X.; Feng, N.P.; Zhao, J.H.; Wu, S.; Tan, R. An improved formulation screening and optimization method applied to the development of a self-microemulsifying drug delivery system. Chem. Pharm. Bull. (Tokyo), 2010, 58(1), 16-22.
[http://dx.doi.org/10.1248/cpb.58.16] [PMID: 20045959]
[41]
Shah, S.; Parmar, B.; Soniwala, M.; Chavda, J. Design, optimization, and evaluation of lurasidone hydrochloride nanocrystals. AAPS Pharm. SciTech, 2016, 17(5), 1150-1158.
[http://dx.doi.org/10.1208/s12249-015-0449-z] [PMID: 26586537]
[42]
Sharma, A.; Sharma, S.; Khuller, G.K. Lectin-functionalized poly (lactide-co-glycolide) nanoparticles as oral/aerosolized antitubercular drug carriers for treatment of tuberculosis. J. Antimicrob. Chemother., 2004, 54(4), 761-766.
[http://dx.doi.org/10.1093/jac/dkh411] [PMID: 15329364]
[43]
Booysen, L.L.I.J.; Kalombo, L.; Brooks, E.; Hansen, R.; Gilliland, J.; Gruppo, V.; Lungenhofer, P.; Semete-Makokotlela, B.; Swai, H.S. in vivo/in vitro pharmacokinetic and pharmacodynamic study of spray-dried poly-(dl-lactic-co-glycolic) acid nanoparticles encapsulating rifampicin and isoniazid. Int. J. Pharm., 2013, 444(1-2), 10-17.
[44]
Yang, W.; Tam, J.; Miller, D.A.; Zhou, J.; McConville, J.T.; Johnston, K.P.; Williams, R.O., III High bioavailability from nebulized itraconazole nanoparticle dispersions with biocompatible stabilizers. Int. J. Pharm., 2008, 361(1-2), 177-188.
[http://dx.doi.org/10.1016/j.ijpharm.2008.05.003] [PMID: 18556158]
[45]
Riley, T.; Christopher, D.; Arp, J.; Casazza, A.; Colombani, A.; Cooper, A.; Dey, M.; Maas, J.; Mitchell, J.; Reiners, M.; Sigari, N.; Tougas, T.; Lyapustina, S. Challenges with developing in vitro dissolution tests for Orally Inhaled Products (OIPs). AAPS Pharm. SciTech, 2012, 13(3), 978-989.
[http://dx.doi.org/10.1208/s12249-012-9822-3] [PMID: 22798037]
[46]
Sreekumar, S.; Goycoolea, F.M.; Moerschbacher, B.M.; Rivera-Rodriguez, G.R. Parameters influencing the size of chitosan-TPP nano- and microparticles. Sci. Rep., 2018, 8(1), 4695.
[http://dx.doi.org/10.1038/s41598-018-23064-4] [PMID: 29549295]
[47]
Lee, E.; Park, S.J.; Lee, J.H.; Kim, M.S.; Kim, C-H. Preparation of chitosan–tpp nanoparticles and their physical and biological properties. Asian J. Pharm. Sci., 2016, 11(1), 166-167.
[http://dx.doi.org/10.1016/j.ajps.2015.11.065]
[48]
Agnihotri, S.A.; Mallikarjuna, N.N.; Aminabhavi, T.M. Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J. Control. Release, 2004, 100(1), 5-28.
[http://dx.doi.org/10.1016/j.jconrel.2004.08.010] [PMID: 15491807]
[49]
Rázga, F.; Vnuková, D.; Némethová, V.; Mazancová, P.; Lacík, I. Preparation of chitosan-TPP sub-micron particles: Critical evaluation and derived recommendations. Carbohydr. Polym., 2016, 151, 488-499.
[http://dx.doi.org/10.1016/j.carbpol.2016.05.092] [PMID: 27474593]
[50]
Hu, B.; Pan, C.; Sun, Y.; Hou, Z.; Ye, H.; Zeng, X.; Zeng, X. Optimization of fabrication parameters to produce chitosan-tripolyphosphate nanoparticles for delivery of tea catechins. J. Agric. Food Chem., 2008, 56(16), 7451-7458.
[http://dx.doi.org/10.1021/jf801111c] [PMID: 18627163]
[51]
Hashad, R.A.; Ishak, R.A.H.; Fahmy, S.; Mansour, S.; Geneidi, A.S. Chitosan-tripolyphosphate nanoparticles: Optimization of formulation parameters for improving process yield at a novel pH using artificial neural networks. Int. J. Biol. Macromol., 2016, 86, 50-58.
[http://dx.doi.org/10.1016/j.ijbiomac.2016.01.042] [PMID: 26783636]
[52]
Cerchiara, T.; Abruzzo, A.; di Cagno, M.; Bigucci, F.; Bauer-Brandl, A.; Parolin, C.; Vitali, B.; Gallucci, M.C.; Luppi, B. Chitosan based micro- and nanoparticles for colon-targeted delivery of vancomycin prepared by alternative processing methods. Eur. J. Pharm. Biopharm., 2015, 92, 112-119.
[http://dx.doi.org/10.1016/j.ejpb.2015.03.004] [PMID: 25769679]
[53]
U.S. Food and Drug Administration. Levaquin. Prescr. Inf., 2008, 1-65.
[54]
Du, Z.; Liu, J.; Zhang, T.; Yu, Y.; Zhang, Y.; Zhai, J.; Huang, H.; Wei, S.; Ding, L.; Liu, B. A study on the preparation of chitosan-tripolyphosphate nanoparticles and its entrapment mechanism for egg white derived peptides. Food Chem., 2019, 286, 530-536.
[http://dx.doi.org/10.1016/j.foodchem.2019.02.012] [PMID: 30827643]
[55]
Gan, Q.; Wang, T. Chitosan nanoparticle as protein delivery carrier-systematic examination of fabrication conditions for efficient loading and release. Colloids Surf. B Biointerfaces, 2007, 59(1), 24-34.
[http://dx.doi.org/10.1016/j.colsurfb.2007.04.009] [PMID: 17555948]
[56]
Jafarinejad, S.; Gilani, K.; Moazeni, E.; Ghazi-Khansari, M.; Najafabadi, A.R.; Mohajel, N. Development of chitosan-based nanoparticles for pulmonary delivery of itraconazole as dry powder formulation. Powder Technol., 2012, 222, 65-70.
[http://dx.doi.org/10.1016/j.powtec.2012.01.045]
[57]
Sabbagh, H.A.K.; Abudayeh, Z.; Abudoleh, S.M.; Alkrad, J.A.; Hussein, M.Z.; Hussein-Al-Ali, S.H. Application of multiple regression analysis in optimization of metronidazole-chitosan nanoparticles. J. Polym. Res., 2019, 26(8), 205.
[http://dx.doi.org/10.1007/s10965-019-1854-x]
[58]
Pandey, P.; Chellappan, D.K.; Tambuwala, M.M.; Bakshi, H.A.; Dua, K.; Dureja, H. Central composite designed formulation, characterization and in vitro cytotoxic effect of erlotinib loaded chitosan nanoparticulate system. Int. J. Biol. Macromol., 2019, 141, 596-610.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.09.023] [PMID: 31494160]
[59]
Rawal, T.; Patel, S.; Butani, S. Chitosan nanoparticles as a promising approach for pulmonary delivery of bedaquiline. Eur. J. Pharm. Sci., 2018, 124, 273-287.
[http://dx.doi.org/10.1016/j.ejps.2018.08.038] [PMID: 30176365]
[60]
Pourshahab, P.S.P.S.; Gilani, K.; Moazeni, E.; Eslahi, H.; Fazeli, M.R.; Jamalifar, H. Preparation and characterization of spray dried inhalable powders containing chitosan nanoparticles for pulmonary delivery of isoniazid. J. Microencapsul., 2011, 28(7), 605-613.
[http://dx.doi.org/10.3109/02652048.2011.599437] [PMID: 21793647]
[61]
Kamaly, N.; Yameen, B.; Wu, J.; Farokhzad, O.C. Degradable controlled-release polymers and polymeric nanoparticles: Mechanisms of controlling drug release. Chem. Rev., 2016, 116(4), 2602-2663.
[http://dx.doi.org/10.1021/acs.chemrev.5b00346] [PMID: 26854975]

Rights & Permissions Print Cite
Article Metrics
8
© 2024 Bentham Science Publishers | Privacy Policy