FORMULATION AND EVALUATION OF AMPHOTERICIN B AND MILTEFOSINE COMBINATION NANOVESICLES
DOI:
https://doi.org/10.22159/ijap.2021v13i3.40605Keywords:
Nanovesicles, AmB-MTF, Ethanol injection method, LeishmaniasisAbstract
Objective: The aim of the present investigation is to formulate and evaluate amphotericin B-miltefosine combination nanovesicles for application in the treatment of visceral leishmaniasis.
Methods: Amphotericin B-miltefosine combination (AmB-MTF) nanovesicles were prepared by ethanol injection method. Formulations of nanovesicles were evaluated at varying conditions of lipids composition, drug-lipid proportion, ethanol-water composition and stirring rate, on drug entrapment efficiency and particle size.
Results: The study showed that entrapment efficiency was significantly affected (p<0.01) by the effects of lipids composition, drug-lipid proportion, ethanol-water composition, and stirring rate. Particle size of nanovesicles was significantly affected (p<0.05) by drug-lipid proportion and stirring rate. An optimized formulation of amphotericin B-miltefosine nanovesicles was prepared at optimal factors composition of: phosphatidylcholine-cholesterol-stearic acid 20:4:1, drug-lipid 1:8, AmB-MTF 1:1; ethanol-water 1:4 ratios, and stirring rate 1000 rpm. The AmB-MTF 1:1 nanovesicles formulation showed particle size of 145.6 nm, poly dispersity index 0.19, zeta potential-27.3 mV and drug entrapment efficiency 87%.
Conclusion: Evaluation of AmB-MTF 1:1 nanovesicles showed development of a successful formulation with very good compatibility, extended drug release, convenient vesicle size and high drug entrapment efficiency. To conclude, AmB-MTF 1:1 nanovesicles formulation could be a safe and reliable therapeutic option over the conventional combination therapy provided further antileishmanial investigations are investigated in vitro and in vivo
Downloads
References
Musa A, Khalil E, Hailu A. Sodium stibogluconate-paromomycin combination for visceral leishmaniasis in East Africa randomized controlled trial. PLoS Negl Trop Dis 2012;6:1674.
WHO. Leishmaniasis. Available from: https://www.who.int/ news-room/fact-sheets/detail/leishmaniasis. [Last accessed on 12 Mar 2019].
Date AA, Joshi MS, Patravale VB. Parasitic diseases: liposomes and polymeric nanoparticles versus lipid nanoparticles. Adv Drug Delivery Rev 2007;59:505–21.
Wagner V, Minguez Menendez A, Pena J, Fernandez Prada C. Innovative solutions for the control of leishmaniases: nanoscale drug delivery. Curr Pharm Design 2019;25:1582-92.
Purkait B, Kumr A, Nandi N, Sardar A, Das S, Kumar S, et al. Mechanism of amphotericin B resistance in clinical isolates of leishmanial donovani. Antimicrob Agents Chemother 2012;56:1031-41.
Shaw CD, Carter KC. Drug delivery: lessons to be learnt from Leishmania studies. Nanomedicine 2014;9:1531-44.
Tanga J, Srinivasanb S, Yuana W, Minga R. Development of a flow-through USP 4 apparatus drug release assay for the evaluation of amphotericin B liposome. Eur J Pharm Biopharm 2019;134:107–16.
Lankalapalli S, Tenneti VS, Nimmali SK. Design and development of vancomycin liposomes. Indian J Pharm Edu Res 2015;49:208-15.
Bose P, Kumar P, Dwivedi M. Hemoglobin guided nanocarrier for specific delivery of amphotericin B to Leishmania infected macrophage. Acta Trop 2016;15:148-59.
Momeni A, Rasoolian M, Momeni A, Navaei A. Development of liposomes loaded with antileishmanial drugs for the treatment of cutaneous leishmaniasis. J Liposome Res 2013;23:134–44.
AL-Quadeib BT, Radwan MA, Siller L, Horrocks B, Wrightd MC. Stealth amphotericin B nanoparticles for oral drug delivery: In vitro optimization. Saudi Pharm J 2015;23:290–302.
Wan S, Zhang L, Quan Y, Wei K. Resveratrol-loaded PLGA nanoparticles: enhanced stability, solubility and bioactivity of resveratrol for non-alcoholic fatty liver disease therapy. Royal Soc Open Sci 2018;5:18145.
Batzri S, Korn D. Single bilayer liposomes prepared without sonication. BBA–Biomembranes 1973;298:1015–9.
Ong S, Ming L, Lee K, Yuen K. Influence of the encapsulation efficiency and size of liposome on the oral bioavailability of griseofulvin-loaded liposomes. Pharmaceutics 2016;8:25.
Yang K, Delaney JT, Schubert US, Fahr A. Fast high-throughput screening of temoporfin-loaded liposomal formulations prepared by ethanol injection method. J Liposome Res 2012;22:31–41.
El-Say KM, Ahmed OA, Mohamed AI, Safo MK, Omar AM. El-Say KM, et al. Zein alpha lipoic acid-loaded nanoparticles to enhance the oral bioavailability of dapoxetine: optimization and clinical pharmacokinetic evaluation. Int J Nanomed 2019;14:7461-73.
Shariare MH, Blagden N, De Matas M, Leusen F. The impact of formulation attributes and process parameters on black seed oil loaded liposomes and their performance in animal models of analgesia. Saudi Pharm J 2012;25:404-12.
Venkata NJ, Prasanna PM, Sakarkar SN, Prabha KS, Ramaiah PS. Microencapsulation techniques, factors influencing encapsulation efficiency. J Microencapsulation 2010;27:187–97.
Hsieh YF, Chen TL, Wang YT, Chang JH, Chang HM. Properties of liposomes prepared with various lipids. J Food Sci 2002;67:2808-13.
Cengiz A, Kahyaoglu T, Schröenb C, Berton Carabin C. Oxidative stability of emulsions fortified with iron: the role of liposomal phospholipids. J Sci Food Agric 2019;99:2957–65.
Italia JL, Sharp A, Carter KC, Warn P, Kumar R. Peroral amphotericin b polymer nanoparticles lead to comparable or superior in vivo antifungal activity to that of intravenous Ambisome® or Fungizone™. Plosone 2011;6:1-11.
Kaur R, Sharma N, Tikoo K, Sinha VR. Development of mirtazapine loaded solid lipid nanoparticles for topical delivery: optimization, characterization and cytotoxicity evaluation. Int J Pharm 2020;586:119439.
Danaei M, Dehghankhold M, Hasanzadeh AF, Javanmard DR, Mozafari MR. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 2018;10:57.
Alonso L, Jeferson E, Cardoso S. Interactions of miltefosine with erythrocyte membrane proteins compared to those of ionic surfactants. Colloidal Surfaces B 2019;180:23-30.
Efentakis M, Al-Hmoud H, Buckton G, Rajan Z. The influence of surfactants on drug release from a hydrophobic matrix. Int J Pharm 1991;70:153-8.
Alvarez Berrios M, Aponte Reyes L, Diaz Figueroa L, Vivero Escoto J, Johnston A, Sanchez Rodriguez D. Preparation and in vitro evaluation of alginate microparticles containing amphotericin b for the treatment of candida infections. Int J Biomater 2020. https://doi.org/10.1155/2020/2514387.
D’Souza S. A review of in vitro drug release test methods for nano-sized dosage forms. Adv Pharm 2014:1-12. https://doi.org/10.1155/2014/304757.
Dorlo T, Eggelte T, Vriesa P, Beijnen J. Characterization and identification of suspected counterfeit miltefosine capsules. Analyst 2012;137:1265–74.
Kunasekaran V, Krishnamoorthy K. Compatibility studies of rasagiline mesylate with selected excipients for an effective solid lipid nanoparticles formulation. Int J Pharm Pharm Sci 2015;7:73-80.
Dawood NM, Abdal-Hammid SN, Hussien AA. Formulation and characterization of lafutidine nanosuspension for oral drug delivery system. Int J Appl Pharm 2018;10:10-30.
Published
How to Cite
Issue
Section
