Formulation of Lecithin-Based Nanocapsules of Levofloxacin and In Vitro Evaluation of the Anti-Mycobacterium Potentials
Article Sidebar
Main Article Content
Abstract
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. Multidrug resistant TB (MDR-TB) remains a public health crisis. The aim of this study was to formulate and evaluate the anti-mycobacterium activity of levofloxacin (LVF) nano formulations against mycobacterium isolates. A 10 g quantity of the lecithin powder was placed in a beaker and 50 mL quantity of water added and heated on a water bath at 55oC for 30 minutes. The oil and water phases were separated by centrifugation at 3000 rpm for 30 minutes. The gum/crude lecithin was dried in vacuum oven for 1 hour at 40 oC. The solvent and lecithin were separated by decantation. The acetone was removed by heating at low temperature at 40 oC and the powdered lecithin was packaged in screw-capped containers until further use. The percentage yield of the extracted lecithin ranged from 31.0±0.31% to 35.0±0.32%. The differential scanning calorimetry (DSC) thermograph of pure LVF showed two sharp endothermic peaks at 225.7oC and 227.8oC. The drug content of levofloxacin formulation using extracted lecithin (LEL) and levofloxacin formulation using reference lecithin (LRL) ranged from 96.9±0.17% to 98.6±0.12% respectively. The LVF nano capsules had activities against the mycobacterial isolates with minimum inhibitory concentrations (MICs) of 26.9μg/mL for LEL and 58.3μg/mL for LRL. The chitosan-fortified nano capsule formulation of LVF has potentials for further exploration and development for enhanced bioavailability and application against MDR-TB.
Downloads
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
Chakaya J, Petersen E, Nantanda R, Mungai BN, Migliori GB, Amanullah F, Lungu P, Ntoumi F, Kumarasamy N, Maeurer M, Zumla A. The WHO Global Tuberculosis 2021 Report - not so good news and turning the tide back to end TB, Int J. Infect Dis. 2022; 124: 26–29. Doi: https://doi.org/10.1016/j.
Migliori GB, Caminero LJ, Kurhasani X, Van DM, Visca D, D’Ambrosi L. History of prevention, diagnosis, treatment and rehabilitation of pulmonary sequelae of tuberculosis. Presse Med 2022; 51:104-112, Doi: http://dx.doi.org/10.1016/j.lpm.2022.104112
Global Tuberculosis Report, Article 1. Available at: https://www.who.int. Global Tuberculosis Report 2023 (WHO.Int), 2023.
Boccia D, Bond V. The catastrophic cost of tuberculosis: advancing research and solutions. Int J Tuberc. Lung Dis. 2019; 23 (11):1129–1130. Doi: http://dx.doi.org/10.5588/ijtld.19.0521.
Espinosa PJ, Sánchez MA, Aznar ML, Espiau M. MDR tuberculosistreatment. Medicina. 2022; 58 (2): 1-34. Doi: http://dx.doi.org/ 10.3390/medicina58020188
Turkova A, Wills GH, Wobudeya E, Chabala C, Palmer M, Kinikar A, Hissar S, Choo L, Musoke P, Veronica M, Mave V, Bency J, Lebeau K, Thomason M, Mboizi RB, Kapasa M, Zalm MM, Raichur P, Bhavani P, Mcilleron H, Demers AM, Aarnoutse R, Koh JL, Seddon J, Welch SB, Grahem SM, Hesseling AC, Gibb DM, Crook AM, Team ST. Shorter treatment for non-severe tuberculosis in African and Indian children. N Engl J Med. 2022; 386:911–922. Doi: http://dx.doi.org/10.1056/nejmoa2104535
Park S, Jo KW, Lee SD, Kim WS, Shim TS. Treatment outcomes of rifampin sparing treatment in patients with pulmonary tuberculosis with rifampin mono-resistance or rifampin adverse events: a retrospective cohort analysis. Respir Med. 2017;131: 43–48. Doi: http://dx.doi.org/10.1016/j.rmed.2017.08.002
Ezegbe CA, Ezegbe AG, Mbah CC, Okorafor CE, Ofoefule IS. Adv. Biochem. Green Production and Preliminary Evaluation of some Physic-chemical Properties of lecithin from locally-sourced soybean (Glycine max) in Nigeria. 2022; 10 (2): 52-58. Doi: https://doi.org/10.11648/j.ab.20221002.13
Rich ML, Khan U, Zeng C, LaHood A, Franke MF, Atwood S, Bastard M, Burhan E, Daniehan N, Dzhazibekova MP, Gadissa D, Ghafoor A, Hewison C, Islam MS, Kazmi E, Khan PY, Lecca L, Maama LB, Melikyan N, NaingYY, Philippe K, Saki NA, Seung KJ, Skrahina A, Tefera GB, Varaine F, Vilbrun SC, Mitnick CD, Huerga H. Outcomes of WHO-conforming, longer, all-oral multidrug-resistant TB regimens and analysis implications. Int J. Tuberc Lung Dis. 2023; 27:451–457. Doi: http://dx.doi.org/10.5588/ijtld.22.0613.
Regazzi M, Carvalho AC, Villani P, Matteelli A. Treatment optimization in patients co-infected with HIV and Mycobacterium tuberculosis infections: focus on drug-drug interactions with rifamycins. Clin Pharmacokinet. 2014; 53:489–507, http://dx.doi.org/10.1007/s40262-014-0144-3.
Ezegbe, CA, Mbah CC, Ezegbe AG, Ofoefule IS. Development and characterization of lecithin based nanoformulation for enhanced delivery of isoniazid in the treatment of tuberculosis. Indo Am J P Sci. 2021; 08 (12), 35-52 Doi: https://doi.org/10.5281/zenodo.5764659.
Sekaggya WC, Nabisere R, Musaazi J, Otaalo B, Aber F, Alinaitwe L, Nampala J, Najjemba L, Buzibye A, Omali D, Gausi K, Kengo A, Lamorde M, Aarnovtse R, Denti P, Dooley EK, Sloan DJ. Decreased dolutegravir and efavirenz concentrations with preserved virological suppression in patients with tuberculosis and human immune deficiency virus receiving high-dose rifampicin. Clin Infect Dis. 2023; 76: 910–919. Doi: http://dx.doi.org/10.1093/cid/ciac585
Eshratabadi P, Sarrafzadeh MH, Fatemi H, Ghavami M, Zanjani GN. Effect of different parameters on removal and quality of soybean lecithin. Iran. J. Chem. Engr. 2008;3 (8): 874-879.
Nasir MI, Bernards MA, Charpentier, PA. Acetylation of soybean lecithin and identification of components for solubility in supercritical carbon dioxide. J. Agric Food Chem.2007;55 (5): 1961-1969.
Milwidsky, BM, Gabriel, DM. Detergent analysis. (A Handbook for cost-effective quality control). 1982; Pp 187-234.
Cynthia VI, Martin B, Cecile ME, Wouter H, Neeitje C, Jakko VI, Sjoert P, Pascal W, Frank S, Rob A, Mihai GN, Reinout VC, Arjan VL Interleukin-1 receptor antagonist anakinra as treatment for paradoxical responses in HIV-negative tuberculosis patients: a case series. Med (NY). 2022; 3 (9): 603–611.Doi: http://dx.doi.org/10.1016/j.medj.2022.07.001.
Nahid P, Dorman SE, Alipanah N, Barry PM, Brozek JL, Cattamanchi A, Lelia HC, Richard EC, Charles LD, Malgosia G, Julie MH, Christine SH, Philip CH, Salmaan AK, Christian L, Richard M, Cynthia M, Masahiron N, Rick OB, Charles AP, Ann R, Jussi S, Simon SH, Giovanni S, Jeffrey RS, Giovanni BM, Andrew V. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis. 2016; 63 (7): 147–195. Doi: http://dx.doi.org/10.1093/cid/ciw376.
Nunn AJ, Phillips PJ, Mitchison DA. Timing of relapse in short-course chemotherapy trials for tuberculosis. Int J Tuberc Lung Dis. 2010; 14:241–250.
Knut L, Mario R. WHO’s new end TB strategy. Trans R Soc. Trop Med Hyg 2016; (3) 148-150 Doi:10.1093/trstmh/trv108.
Guan J, Cheng P, Huang S, Wu J, Li Z and You X. Optimized preparation of levofloxacin-loaded chitosan nanoparticles by mechanical dispersion method. Phys. Procedia. 2011; 22:163-169.
Xiong XB, Binkhathlan Z, Molavi O, Lavasanifar A. Amphiphilic block co-polymers: Preparation and application in nano drug and gene delivery. Acta Biomater 2012; 8: 2017-2033.
Horter S, Daftary A, Keam T, Bernays S, Bhanushali K, Chavan D. Denhokn J, Furin J, Jaramillo E, Khan A, Lin YD, Lobo R, Triasih R, Venkatesan N, Viney K, Cros P. Person-centered care in TB. Int J. Tuberc Lung Dis. 2021; 25:784–787. Doi: http://dx.doi.org/10.5588/ijtld.21.0327.
Saluzzo F, Espinosa PJ, Dressler S, Tàvora DS, Filho E, Seidel S, Gonzalez MJ. Community engagement in tuberculosis research: the EU-Patient-cEntricclinicAltRialpLatforms (EU-PEARL) experience. Int J Infect Dis. 2023; 130: 20–24. Doi: http://dx.doi.org/10.1016/j.ijid.2023.03.008
British Pharmacopoeia. British Pharmacopoeia, vol. III. London. Her Majesty’s Stationery Office. 2009; 6578-6585.
Gaurav K, Sadhnas S, Nusrat S, Gopal K, Samiv M. Optimisation, in vitro-in vivo evaluation and short-term tolerability of novel levofloxacin-loaded PLGA nanoparticles formulation. Journal of Phar. Sci. 2002; 101: 2165-2176
Chesov E, Chesov D, Maurer FP, Andres S, Utpatel C, Barilar I., Donica A, Reimann M, Niemann S, Lange C, Crudu V, Heyckendorf J, Mathias M. Emergence of bedaquiline resistance in a high tuberculosis burden country. Eur Respir J. 2022; 59-67. Doi: http://dx.doi.org/10.1183/13993003.00621-2021.
Korsmeyers RW, Gumy R, Doelker EM, Buri P and PeppasNA . Mechanism of drug release from porous hydrophilic polymers Int J Pharm. 1983; 15: 25-35.
Palomino JC, Martin A, Camacho M, Guerra H, Swings J, Portaels F. Resazurinmcrotiter assay plate: Simple and inexpensive method for detection of drug-resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2002; 46: 2720-2722.
Pires CT, Mislane AB, Regiane B, Diogenes A, Luciana D, Vera L, Rosilene F. Anti-mycobacterium tuberculosis activity and cytotoxicity of CalophyllumbrasilienseCambess(Clusiaceae). Mem Inst. Oswaldo Cruz, Rio de Janeiro. 2014; 109 (3): 324-329.
Beny B, Nagaraja S, Korlakunta N, Abin A. Formulation and evaluation of levofloxacin nanoparticles by ionic gelation method. J. Pharm Pharma Sci.2012; 1: 1-15.
Onorato L, Gentile V, Russo A, di Caprio G, Alessio L, Chiodini P. Standard versus high dose of rifampicin in the treatment of pulmonary tuberculosis: a systematic review and meta-analysis. Clin Microbiol Infect. 2021; 27:830–837. Doi: http://dx.doi.org/10.1016/j.cmi.2021.03.031.
Rojanarat W and Nakpheng T. Levofloxacin – proliposomes-oppurtunities for use in lung tuberculosis. Pharmaceutics. 2012; 4:385–412.
Ramadoss A. B; Sathya R; Radhakrishnan R. Levofloxacin: formulation and in-vitro evaluation of alginate and chitosan nanospheres Egyptian Pharma J. 2015; 14:30–35.
Allwood BW, Byrne A, Meghji J, Rachow A, van der Zalm MM, Schoch OD. Post tuberculosis lung disease: clinical review of an under-recognized global challenge. Respiration. 2021; 100:751–763. Doi: http://dx.doi.org/10.1159/000512531
Zhou SB, Deng XM, Li X. Investigation on a novel core-coated microspheres protein delivery system. J Control Release. 2001; 75:27-36.
Rastogi N, Goh K.S, Bryskier A, Devallois A. Antimicrobial Agents and Chemotherapy. American Society for Microbiology. 1996; 40 (11). 2483-2487.
Rachow A, Ivanova O, Wallis R, Charalambous S, Jani I, Bhatt N. TB sequel: incidence, pathogenesis and risk factors of long-term medical and social sequelae of pulmonary TB - a study protocol. BMC Pulm Med. 2019; 19:1-9. Doi: http://dx.doi.org/10.1186/s12890-018-0777-3