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Pharmaceutical Nanotechnology

Editor-in-Chief

ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

Research Article

In vitro/In vivo Evaluation of Elastic Nano-lipid Carriers of Aztreonam for Pneumonic Lungs

Author(s): Sayani Bhattacharyya*

Volume 11, Issue 3, 2023

Published on: 28 March, 2023

Page: [294 - 302] Pages: 9

DOI: 10.2174/2211738511666230223141759

Price: $65

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Abstract

Background: The liposomal inhalation of drugs has been extensively researched for the invasion of biofilms and macrophages in the infected lungs.

Objective: The present study aimed to explore the in vitro and in vivo effects of elastic nano-lipid vesicles of aztreonam for pulmonary delivery.

Methods: Elastic nano lipid vesicles of the drug were successfully prepared with the commonly abundant lung phospholipids (LIPOID S PC-3, LIPOID PC 16:0/16:0), cholesterol, and span 20. Four such formulations were evaluated for their physicochemical properties, in vitro diffusion, and cytotoxicity. The best formulation was subjected to stability, in vivo drug deposition on the pneumonic lungs, and histopathological studies.

Results: The characterization of the lipid vesicles in terms of particle size, zeta potential, and surface morphology confirmed the formation of stable nanolipid vesicles of the drug. The presence of surfactant in the lipid vesicles exhibited high bilayer stability, entrapment, and diffusion of the drug. The in vitro diffusion study revealed the biphasic characteristic with an initial burst, followed by sustenance for 8 h. A remarkable drug uptake was observed in the epithelial cell line of CHO Cricetulus griseus in the presence of surfactant. The drug was retained on the pneumonic lungs for 8 h. The histopathological study of lung tissue revealed that surfactant-based lipid vesicles could attenuate lung fibrosis significantly.

Conclusion: It can be concluded that elastic nano lipid vesicular system of aztreonam could be a paradigm for targeting and localization of the drug with a long residence time in the lungs.

Graphical Abstract

[1]
Boucher BA. Role of aztreonam in the treatment of nosocomial pneumonia in the critically ill surgical patient. Am J Surg 2000; 179(2): 45-50.
[http://dx.doi.org/10.1016/S0002-9610(00)00321-4] [PMID: 10874114]
[2]
Aztreonam | DrugBank Online. Available from: https://go.drugbank.com/drugs/DB00355
[3]
Rowe S, Cheadle WG. Complications of nosocomial pneumonia in the surgical patient. Am J Surg 2000; 179(2): 63-8.
[http://dx.doi.org/10.1016/S0002-9610(00)00323-8] [PMID: 10802269]
[4]
Cipolla D, Wu H, Eastman S, Redelmeier T, Gonda I, Chan HK. Development and characterization of an in vitro release assay for liposomal ciprofloxacin for inhalation. J Pharm Sci 2014; 103(1): 314-27.
[http://dx.doi.org/10.1002/jps.23795]
[5]
Ye T, Yu J, Luo Q, Wang S, Chan HK. Inhalable clarithromycin liposomal dry powders using ultrasonic spray freeze drying. Powder Technol 2017; 305: 63-70.
[http://dx.doi.org/10.1016/j.powtec.2016.09.053]
[6]
Cipolla D, Gonda I, Chan HK. Liposomal formulations for inhalation. Ther Deliv 2013; 4(8): 1047-72.
[http://dx.doi.org/10.4155/tde.13.71] [PMID: 23919478]
[7]
Zhang J, Leifer F, Rose S, et al. Amikacin liposome inhalation suspension (ALIS) penetrates non-tuberculous mycobacterial biofilms and enhances amikacin uptake into macrophages. Front Microbiol 2018; 9: 915.
[http://dx.doi.org/10.3389/fmicb.2018.00915] [PMID: 29867826]
[8]
Joshi N, Shirsath N, Singh A, Joshi KS, Banerjee R. Endogenous lung surfactant inspired pH responsive nanovesicle aerosols: Pulmonary compatible and site-specific drug delivery in lung metastases. Sci Reports 2014; 1-11.
[http://dx.doi.org/10.1038/srep07085]
[9]
Webster T, Singh S, Vardhan H, Kotla N, Maddiboyina B, Sharma D. The role of surfactants in the formulation of elastic liposomal gels containing a synthetic opioid analgesic. Int J Nanomedicine 2016; 11: 1475-82.
[http://dx.doi.org/10.2147/IJN.S100253] [PMID: 27114707]
[10]
Lichtenberg D, Ahyayauch H, Goñi FM. The mechanism of detergent solubilization of lipid bilayers. Biophys J 2013; 105(2): 289-99.
[http://dx.doi.org/10.1016/j.bpj.2013.06.007] [PMID: 23870250]
[11]
Lichtenberg D, Robson RJ, Dennis EA. Solubilization of phospholipids by detergents structural and kinetic aspects. Biochim Biophys Acta Rev Biomembr 1983; 737(2): 285-304.
[http://dx.doi.org/10.1016/0304-4157(83)90004-7] [PMID: 6342675]
[12]
Shaker S, Gardouh A, Ghorab M. Factors affecting liposomes particle size prepared by ethanol injection method. Res Pharm Sci 2017; 12(5): 346-52.
[http://dx.doi.org/10.4103/1735-5362.213979] [PMID: 28974972]
[13]
Cipolla D, Wu H, Gonda I, Eastman S, Redelmeier T, Chan HK. Modifying the release properties of liposomes toward personalized medicine. J Pharm Sci 2014; 103(6): 1851-62.
[http://dx.doi.org/10.1002/jps.23969] [PMID: 24715635]
[14]
Azactam (aztreonam) dosing, indications, interactions, adverse effects, and more. Available from: https://reference.medscape.com/drug/azactam-aztreonam-342553
[15]
Zhang H. Thin-film hydration followed by extrusion method for liposome preparationMethods Mol Biol. Humana Press Inc. 2017; pp. 17-22.
[http://dx.doi.org/10.1007/978-1-4939-6591-5_2]
[16]
Muranishi Y, Sato T, Ito S, et al. The Ratios of monounsaturated to saturated phosphatidylcholines in lung adenocarcinoma microenvironment analyzed by liquid chromatography-mass spectrometry and imaging mass spectrometry. Sci Rep 2019; 9(1): 8916.
[http://dx.doi.org/10.1038/s41598-019-45506-3] [PMID: 31222099]
[17]
Lasic DD. Mechanisms of liposome formation. J Liposome Res 1995; 5(3): 431-41.
[http://dx.doi.org/10.3109/08982109509010233]
[18]
Lasic DD, Martin FJ. On the mechanism of vesicle formation. J Membr Sci 1990; 50(2): 215-22.
[http://dx.doi.org/10.1016/S0376-7388(00)80317-8]
[19]
He Y, Luo L, Liang S, Long M, Xu H. Influence of probe-sonication process on drug entrapment efficiency of liposomes loaded with a hydrophobic drug. Int J Polym Mater 2019; 68(4): 193-7.
[http://dx.doi.org/10.1080/00914037.2018.1434651]
[20]
Hadian Z, Sahari MA, Moghimi HR, Barzegar M. Formulation, characterization and optimization of liposomes containing eicosapentaenoic and docosahexaenoic acids; A methodology approach. Iran J Pharm Res 2014; 13(2): 393-404.
[PMID: 25237335]
[21]
Sayani Bhattacharyya BSS. Preethi Sudheer, Validation of RP-HPLC methof and UV spectrophotometric methos for the quantitative determination of azteonam in bulk and pharmaceutical dosage form. RGUHS J Pharm Sci 2018; 8: 120-6.
[22]
Shashidhar GM, Manohar B. Nanocharacterization of liposomes for the encapsulation of water soluble compounds from Cordyceps sinensis CS1197 by a supercritical gas anti-solvent technique. RSC Advances 2018; 8(60): 34634-49.
[http://dx.doi.org/10.1039/C8RA07601D] [PMID: 35548621]
[23]
Franzé S, Selmin F, Samaritani E, Minghetti P, Cilurzo F. Lyophilization of liposomal formulations: Still necessary, still challenging. Pharmaceutics 2018; 10(3): 139.
[http://dx.doi.org/10.3390/pharmaceutics10030139] [PMID: 30154315]
[24]
Bhattacharyya SBS. Sayani, validation for quantitative determination of aztreonam in simulated. Int J Pharm Sci Res 2019; 10: 1000-4.
[http://dx.doi.org/10.13040/IJPSR.0975-8232.10(1).1000-05]
[25]
Manca ML, Zaru M, Manconi M, et al. Glycerosomes: A new tool for effective dermal and transdermal drug delivery. Int J Pharm 2013; 455(1-2): 66-74.
[http://dx.doi.org/10.1016/j.ijpharm.2013.07.060] [PMID: 23911913]
[26]
Poelma DLH, Zimmermann LJ, van Cappellen WA, Haitsma JJ, Lachmann B, van Iwaarden JF. Distinct effects of SP-B and SP-C on the uptake of surfactant-like liposomes by alveolar cells in vivo and in vitro. Am J Physiol Lung Cell Mol Physiol 2004; 287(5): L1056-65.
[http://dx.doi.org/10.1152/ajplung.00054.2004] [PMID: 15257983]
[27]
Corsini E, Di Paola R, Viviani B, et al. Increased carrageenan-induced acute lung inflammation in old rats. Immunology 2005; 115(2): 253-61.
[http://dx.doi.org/10.1111/j.1365-2567.2005.02148.x] [PMID: 15885132]
[28]
Sinha B, Mukherjee B, Pattnaik G. Poly-lactide-co-glycolide nanoparticles containing voriconazole for pulmonary delivery: In vitro and in vivo study. Nanomedicine 2013; 9(1): 94-104.
[http://dx.doi.org/10.1016/j.nano.2012.04.005] [PMID: 22633899]
[29]
Patole VC, Pandit AP. Mesalamine-loaded alginate microspheres filled in enteric coated HPMC capsules for local treatment of ulcerative colitis: In vitro and in vivo characterization. J Pharm Investig 2018; 48(3): 257-67.
[http://dx.doi.org/10.1007/s40005-017-0304-1]
[30]
Chow AHL, Tong HHY, Chattopadhyay P, Shekunov BY. Particle engineering for pulmonary drug delivery. Pharm Res 2007; 24(3): 411-37.
[http://dx.doi.org/10.1007/s11095-006-9174-3] [PMID: 17245651]
[31]
Patil S, Sandberg A, Heckert E, Self W, Seal S. Protein adsorption and cellular uptake of cerium oxide nanoparticles as a function of zeta potential. Biomaterials 2007; 28(31): 4600-7.
[http://dx.doi.org/10.1016/j.biomaterials.2007.07.029] [PMID: 17675227]
[32]
Aliasgharlou L, Ghanbarzadeh S, Azimi H, Zarrintan MH, Hamishehkar H. Nanostructured lipid carrier for topical application of N-acetyl glucosamine. Adv Pharm Bull 2016; 6(4): 581-7.
[http://dx.doi.org/10.15171/apb.2016.072] [PMID: 28101465]
[33]
Abdelwahed W, Degobert G, Stainmesse S, Fessi H. Freeze-drying of nanoparticles: Formulation, process and storage considerations. Adv Drug Deliv Rev 2006; 58(15): 1688-713.
[http://dx.doi.org/10.1016/j.addr.2006.09.017] [PMID: 17118485]
[34]
Kang SN, Hong SS, Kim SY, Oh H, Lee MK, Lim SJ. Enhancement of liposomal stability and cellular drug uptake by incorporating tributyrin into celecoxib-loaded liposomes. Asian J Pharm Sci 2013; 8(2): 128-33.
[http://dx.doi.org/10.1016/j.ajps.2013.07.016]

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