Login Register Cart 0
Generic placeholder image

Current Indian Science

Editor-in-Chief

ISSN (Print): 2210-299X
ISSN (Online): 2210-3007

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

Development and Characterization of Linezolid loaded Biocompatible Solidlipid based Nanocarrier for Enhanced Lung Deposition and Anti-tubercular Activity: Next Generation tailor-made Carrier for Dry Powder Inhaler

Author(s): Ravindra N. Kamble*, Eram Kausar, Madhugandha S. Kawadiwale and Ashwin J. Mali

Volume 1, 2023

Published on: 01 August, 2023

Article ID: e080523216630 Pages: 11

DOI: 10.2174/2210299X01666230508103042

Price: $

Abstract

Objective: The objective of the present work was to achieve enhanced site-specific delivery of linezolid (LNZ) to the lung by developing solid lipid nanoparticles (SLN) as a carrier for dry powder inhalers (DPI).

Methods: The LNZ-loaded SLN (LNZ-SLN) were prepared by hot homogenization method by using Stearic acid, Tween 80, and Pluronic F-68 and further compared with the conventional form of DPI. The developed SLN were evaluated for physical characteristics, In vitro diffusion study, In vitro lung deposition by Andersen Cascade Impactor (ACI), In vitro cell viability study, and acute toxicity of lung tissues.

Results: The particle size, zeta potential, mass median aerodynamic diameter, and fine particle fraction of the DPI were found to be 1.23 ± 0.07 μm, -10 mV, 1.02 ± 0.04 μm, 44.17 ± 0.73% respectively which revealed the potential for pulmonary delivery. The encapsulation efficiency was 81 ± 2.08% and the biphasic release pattern was observed from prepared SLN at pH 7.4.

Conclusion: The initial burst release of 30% and followed by controlled release (100%) was observed for 72h. Differential scanning calorimetry and powder Xray diffraction pointed out the amorphous nature of the LNZ. The Transmission electron microscopy and Scanning electron microscopy reflected the encapsulation of LNZ in SLN. Furthermore, In vitro cell viability study and the histopathological study revealed the biocompatibility and safety of the formulation. The LNZ-SLN DPI ascertained an improved lung deposition with controlled release and the least toxicity as compared to the conventional form of DPI which confirmed its feasibility for pulmonary administration.

[1]
Cruz-Knight, W.; Blake-Gumbs, L. Tuberculosis. Prim. Care, 2013, 40(3), 743-756.
[http://dx.doi.org/10.1016/j.pop.2013.06.003] [PMID: 23958367]
[2]
Kaur, M.; Garg, T.; Narang, R.K. A review of emerging trends in the treatment of tuberculosis. Artif. Cells Nanomed. Biotechnol., 2016, 44(2), 478-484.
[http://dx.doi.org/10.3109/21691401.2014.962745] [PMID: 25365354]
[3]
Kaur, M; Garg, T; Rath, G; Goyal, AK Current nanotechnological strategies for effective delivery of bioactive drug molecules in the treatment of tuberculosis. Crit Rev Ther Drug Carrier Syst., 2014, 31(1), 49-88.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.2014008285]
[4]
Available from: https://www.who.int/news-room/fact-sheets/detail/tuberculosis
[5]
Available from: https://tbcindia.gov.in/WriteReadData/l892s/India%20TB%20Report%202020.pdf
[6]
Kaur, R.; Garg, T.; Malik, B.; Gupta, U.D.; Gupta, P.; Rath, G.; Goyal, A.K. Development and characterization of spray-dried porous nanoaggregates for pulmonary delivery of anti-tubercular drugs. Drug Deliv., 2016, 23(3), 872-877.
[http://dx.doi.org/10.3109/10717544.2014.920428] [PMID: 24870203]
[7]
Campbell, I.A.; Bah-Sow, O. Pulmonary tuberculosis: Diagnosis and treatment. BMJ, 2006, 332(7551), 1194-1197.
[http://dx.doi.org/10.1136/bmj.332.7551.1194] [PMID: 16709993]
[8]
Pham, D.D.; Fattal, E.; Tsapis, N. Pulmonary drug delivery systems for tuberculosis treatment. Int. J. Pharm., 2015, 478(2), 517-529.
[http://dx.doi.org/10.1016/j.ijpharm.2014.12.009] [PMID: 25499020]
[9]
WHO. Global tuberculosis control: WHO report. Aust. N. Z. J. Public Health, 2012, 36(5), 497-498.
[http://dx.doi.org/10.1111/j.1753-6405.2012.00928.x]
[10]
Global Tuberculosis Report 2013; WHO: Geneva, Switzerland, 2013.
[11]
Tan, Z.M.; Lai, G.P.; Pandey, M.; Srichana, T.; Pichika, M.R.; Gorain, B.; Bhattamishra, S.K.; Choudhury, H. Novel approaches for the treatment of pulmonary tuberculosis. Pharmaceutics, 2020, 12(12), 1196.
[http://dx.doi.org/10.3390/pharmaceutics12121196] [PMID: 33321797]
[12]
Sulis, G.; Roggi, A.; Matteelli, A.; Raviglione, M.C. Tuberculosis: Epidemiology and control. Mediterr. J. Hematol. Infect. Dis., 2014, 6(1), e2014070.
[http://dx.doi.org/10.4084/mjhid.2014.070] [PMID: 25408856]
[13]
Seung, K.J.; Keshavjee, S.; Rich, M.L. Multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. Cold Spring Harb. Perspect. Med., 2015, 5(9), a017863.
[http://dx.doi.org/10.1101/cshperspect.a017863] [PMID: 25918181]
[14]
Muralidharan, P.; Malapit, M.; Mallory, E.; Hayes, D., Jr; Mansour, H.M. Inhalable nanoparticulate powders for respiratory delivery. Nanomedicine, 2015, 11(5), 1189-1199.
[http://dx.doi.org/10.1016/j.nano.2015.01.007] [PMID: 25659645]
[15]
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]
[16]
Goyal, AK; Garg, T; Bhandari, S; Rath, G Advancement in pulmonary drug delivery systems for treatment of tuberculosis. In: Nanostructures for Drug Delivery; , 2017; pp. 669-695.
[http://dx.doi.org/10.1016/B978-0-323-46143-6.00022-1]
[17]
Sarasija, S.; Patil, J.S. Pulmonary drug delivery strategies: A concise, systematic review. Lung India, 2012, 29(1), 44-49.
[http://dx.doi.org/10.4103/0970-2113.92361] [PMID: 22345913]
[18]
Ekambaram, P. a.; hasansathali, A.; Priyanka, K. Solid lipid nanoparticles: A review. Sci. Revs. Chem. Commun., 2012, 2(1), 80-102.
[19]
Weber, S.; Zimmer, A.; Pardeike, J. Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) for pulmonary application: A review of the state of the art. Eur. J. Pharm. Biopharm., 2014, 86(1), 7-22.
[http://dx.doi.org/10.1016/j.ejpb.2013.08.013] [PMID: 24007657]
[20]
Patil, K.D.; Bagade, S.B.; Bonde, S.C. Biodistribution, pharmacokinetics and toxicity evaluation of mannosylatedgelatin nanoparticles of linezolid for anti-tubercular therapy. Mater. Technol., 2020, 1-9.
[21]
Dryden, M.S. Linezolid pharmacokinetics and pharmacodynamics in clinical treatment. J. Antimicrob. Chemother., 2011, 66(S4), iv7-iv15.
[http://dx.doi.org/10.1093/jac/dkr072] [PMID: 21521707]
[22]
MacGowan, A.P. Pharmacokinetic and pharmacodynamic profile of linezolid in healthy volunteers and patients with Gram-positive infections. J. Antimicrob. Chemother., 2003, 51(90002), 17ii-25.
[http://dx.doi.org/10.1093/jac/dkg248] [PMID: 12730139]
[23]
Estes, K.S.; Derendorf, H. Comparison of the pharmacokinetic properties of vancomycin, linezolid, tigecyclin, and daptomycin. Eur. J. Med. Res., 2010, 15(12), 533-543.
[http://dx.doi.org/10.1186/2047-783X-15-12-533] [PMID: 21163728]
[24]
Shah, S.; Cristopher, D.; Sharma, S.; Soniwala, M.; Chavda, J. Inhalable linezolid loaded PLGA nanoparticles for treatment of tuberculosis: Design, development and In vitro evaluation. J. Drug Deliv. Sci. Technol., 2020, 60, 102013.
[http://dx.doi.org/10.1016/j.jddst.2020.102013]
[25]
Bhardwaj, A.; Kumar, L.; Narang, R.K.; Murthy, R.S.R. Development and characterization of ligand-appended liposomes for multiple drug therapy for pulmonary tuberculosis. Artif. Cells Nanomed. Biotechnol., 2013, 41(1), 52-59.
[http://dx.doi.org/10.3109/10731199.2012.702316] [PMID: 22889361]
[26]
Takeuchi, I.; Taniguchi, Y.; Tamura, Y.; Ochiai, K.; Makino, K. Effects of l-leucine on PLGA microparticles for pulmonary administration prepared using spray drying: Fine particle fraction and phagocytotic ratio of alveolar macrophages. Colloids Surf. A Physicochem. Eng. Asp., 2018, 537, 411-417.
[http://dx.doi.org/10.1016/j.colsurfa.2017.10.047]
[27]
Huang, J.; Chen, Z.; Ying, L.; Li, L.; Zhang, G. Rifapentine-linezolid-loaded PLGA microspheres for interventional therapy of cavitary pulmonary tuberculosis: Preparation and In vitro characterization. Drug Des. Devel. Ther., 2017, 11, 585-592.
[http://dx.doi.org/10.2147/DDDT.S127897] [PMID: 28424536]
[28]
Üner, M.; Yener, G. Importance of solid lipid nanoparticles (SLN) in various administration routes and future perspectives. Int. J. Nanomedicine, 2007, 2(3), 289-300.
[PMID: 18019829]
[29]
Mahajan, P.S.; Mahajan, K.B.; Darekar, A.B. A review on solid lipid nanoparticle (SLN): An advanced treatment modality. Int. J. Pharm. Sci. Res., 2015, 6(9), 3698.
[30]
Li, Y.Z.; Sun, X.; Gong, T.; Liu, J.; Zuo, J.; Zhang, Z.R. Inhalable microparticles as carriers for pulmonary delivery of thymopentin-loaded solid lipid nanoparticles. Pharm. Res., 2010, 27(9), 1977-1986.
[http://dx.doi.org/10.1007/s11095-010-0201-z] [PMID: 20625801]
[31]
Capanoglu, M.; Dibek Misirlioglu, E.; Toyran, M.; Civelek, E.; Kocabas, C.N. Evaluation of inhaler technique, adherence to therapy and their effect on disease control among children with asthma using metered dose or dry powder inhalers. J. Asthma, 2015, 52(8), 838-845.
[http://dx.doi.org/10.3109/02770903.2015.1028075] [PMID: 26037396]
[32]
Garg, T; Kumar, A; Rath, G; Goyal, AK Gastroretentive drug delivery systems for therapeutic management of peptic ulcer. Crit Rev Ther Drug Carrier Syst., 2014, 31(6), 531-57.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.2014011104]
[33]
Gaspar, D.P.; Faria, V.; Gonçalves, L.M.D.; Taboada, P.; Remuñán-López, C.; Almeida, A.J. Rifabutin-loaded solid lipid nanoparticles for inhaled antitubercular therapy: Physicochemical and In vitro studies. Int. J. Pharm., 2016, 497(1-2), 199-209.
[http://dx.doi.org/10.1016/j.ijpharm.2015.11.050] [PMID: 26656946]
[34]
Pokharkar, V.B.; Patil-Gadhe, A.A.; Kyadarkunte, A.Y.; Pereira, M.; Jejurikar, G.; Patole, M.S.; Risbud, A. Rifapentine-proliposomes for inhalation: In vitro and In vivo toxicity. Toxicol. Int., 2014, 21(3), 275-282.
[http://dx.doi.org/10.4103/0971-6580.155361] [PMID: 25948966]
[35]
Wang, S.; Chen, T.; Chen, R.; Hu, Y.; Chen, M.; Wang, Y. Emodin loaded solid lipid nanoparticles: Preparation, characterization and antitumor activity studies. Int. J. Pharm., 2012, 430(1-2), 238-246.
[http://dx.doi.org/10.1016/j.ijpharm.2012.03.027] [PMID: 22465546]
[36]
Mali, A.J.; Pawar, A.P.; Bothiraja, C. Improved lung delivery of budesonide from biopolymer based dry powder inhaler through natural inhalation of rat. Mater. Technol., 2014, 29(6), 350-357.
[http://dx.doi.org/10.1179/1753555714Y.0000000163]
[37]
Bothiraja, C.; Dhage, K.; Kamble, R. D-α-Tocopherol polyethylene glycol succinate and stearoylmacrogol glycerides biomaterial based nanostructured mixed micelles as nose-to-brain targeting drug delivery system. Mater. Technol., 2020, 1-4.
[38]
Kamble, R.; Sharma, S.; Mehta, P. Norfloxacin mixed solvency based solid dispersions: An in-vitro and in-vivo investigation. J. Taibah Univ. Sci., 2017, 11(3), 512-522.
[http://dx.doi.org/10.1016/j.jtusci.2016.11.003]
[39]
Shaji, J.; Kumbhar, M. Formulation and characterization of linezolid loaded Eudragit RS 100 polymeric nanoparticles. Int. J. Pharm. Sci. Res., 2019, 10, 1944-1952.
[40]
Gajra, B.; Patel, R.R.; Dalwadi, C. Formulation, optimization and characterization of cationic polymeric nanoparticles of mast cell stabilizing agent using the Box–Behnken experimental design. Drug Dev. Ind. Pharm., 2016, 42(5), 747-757.
[http://dx.doi.org/10.3109/03639045.2015.1093496] [PMID: 26559522]
[41]
Rawat, M.; Saraf, S. Formulation optimization of double emulsification method for preparation of enzyme-loaded Eudragit S100 microspheres. J. Microencapsul., 2009, 26(4), 306-314.
[http://dx.doi.org/10.1080/02652040802319767] [PMID: 18686142]

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