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Current Drug Delivery

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

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Research Article

Amphotericin B Loaded Nanostructured Lipid Carriers for Parenteral Delivery: Characterization, Antifungal and In vitro Toxicity Assessment

Author(s): Pataranapa Nimtrakul, Waree Tiyaboonchai* and Supaporn Lamlertthon

Volume 16, Issue 7, 2019

Page: [645 - 653] Pages: 9

DOI: 10.2174/1567201816666190729145223

Price: $65

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Abstract

Background: Amphotericin B (AmB) is important for the treatment of systemic fungal infections. Nowadays, only intravenous administration (IV) of AmB has been available due to its low aqueous solubility. Two forms of AmB are available. The first is Fungizone®, a mixture of AmB and sodium deoxcycholate that produces severe nephrotoxicity. The second are lipid-based formulations that reduce nephrotoxicity, but they are costly and require higher dose than Fungizone®. Thus, a cheaper delivery system with reduced AmB toxicity is required.

Objective: To develop and characterize AmB loaded-nanostructured lipid carriers (AmB-loaded NLCs) for IV administration to reduce AmB toxicity.

Methods: AmB-loaded NLCs with different solid lipids were prepared by the high-pressure homogenization technique. Their physicochemical properties and the drug release profile were examined. The molecular structure of AmB, antifungal and hemolysis activities of developed AmB-loaded NLCs were also evaluated.

Results: AmB-loaded NLCs ~110 to ~140 nm in diameter were successfully produced with a zeta potential of ~-19 mV and entrapment efficiency of ~75%. In vitro release showed fast release characteristics. AmB-loaded NLCs could reduce the AmB molecular aggregation as evident from the absorbance ratio of the first to the fourth peak showing a partial aggregation of AmB. This result suggested that AmB-loaded NLCs could offer less nephrotoxicity compared to Fungizone®. In vitro antifungal activity of AmB-loaded NLCs showed a minimum inhibitory concentration of 0.25 µgmL-1.

Conclusion: AmB-loaded NLCs present high potential carriers for effective IV treatment with prolonged circulation time and reduced toxicity.

Keywords: Amphotericin B, nanostructure lipid carriers, antifungal, hemolysis, solid lipid, self-aggregation, nephrotoxicity.

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[1]
Hamill, R.J.; Amphotericin, B. Amphotericin B formulations: a comparative review of efficacy and toxicity. Drugs, 2013, 73(9), 919-934.
[http://dx.doi.org/10.1007/s40265-013-0069-4] [PMID: 23729001]
[2]
Wasan, E.K.; Bartlett, K.; Gershkovich, P.; Sivak, O.; Banno, B.; Wong, Z.; Gagnon, J.; Gates, B.; Leon, C.G.; Wasan, K.M. Development and characterization of oral lipid-based amphotericin B formulations with enhanced drug solubility, stability and antifungal activity in rats infected with Aspergillus fumigatus or Candida albicans. Int. J. Pharm., 2009, 372(1-2), 76-84.
[http://dx.doi.org/10.1016/j.ijpharm.2009.01.003] [PMID: 19236839]
[3]
Sawaya, B.P.; Briggs, J.P.; Schnermann, J. Amphotericin B nephrotoxicity: the adverse consequences of altered membrane properties. J. Am. Soc. Nephrol., 1995, 6(2), 154-164.
[PMID: 7579079]
[4]
Ostrosky-Zeichner, L.; Marr, K.A.; Rex, J.H.; Cohen, S.H.; Cohen, S.H.; Amphotericin, B. Amphotericin B: time for a new “gold standard”. Clin. Infect. Dis., 2003, 37(3), 415-425.
[http://dx.doi.org/10.1086/376634] [PMID: 12884167]
[5]
Sabra, R.; Branch, R.A. Amphotericin B nephrotoxicity. Drug Saf., 1990, 5(2), 94-108.
[http://dx.doi.org/10.2165/00002018-199005020-00003] [PMID: 2182052]
[6]
Fanos, V.; Cataldi, L. Amphotericin B-induced nephrotoxicity: a review. J. Chemother., 2000, 12(6), 463-470.
[http://dx.doi.org/10.1179/joc.2000.12.6.463] [PMID: 11154026]
[7]
Laniado-Laborín, R.; Cabrales-Vargas, M.N.; Amphotericin, B. Amphotericin B: side effects and toxicity. Rev. Iberoam. Micol., 2009, 26(4), 223-227.
[http://dx.doi.org/10.1016/j.riam.2009.06.003] [PMID: 19836985]
[8]
Risovic, V.; Sachs-Barrable, K.; Boyd, M.; Wasan, K.M. Potential mechanisms by which Peceol increases the gastrointestinal absorption of amphotericin B. Drug Dev. Ind. Pharm., 2004, 30(7), 767-774.
[http://dx.doi.org/10.1081/DDC-120039793] [PMID: 15491054]
[9]
Dupont, B. Overview of the lipid formulations of amphotericin B. J. Antimicrob. Chemother., 2002, 49(Suppl. 1), 31-36.
[http://dx.doi.org/10.1093/jac/49.suppl_1.31] [PMID: 11801578]
[10]
Tiyaboonchai, W.; Limpeanchob, N. Formulation and characterization of amphotericin B-chitosan-dextran sulfate nanoparticles. Int. J. Pharm., 2007, 329(1-2), 142-149.
[http://dx.doi.org/10.1016/j.ijpharm.2006.08.013] [PMID: 17000065]
[11]
Rawat, M.; Singh, D.; Saraf, S.; Saraf, S. Lipid carriers: a versatile delivery vehicle for proteins and peptides. Yakugaku Zasshi, 2008, 128(2), 269-280.
[http://dx.doi.org/10.1248/yakushi.128.269] [PMID: 18239375]
[12]
Pardeike, J.; Hommoss, A.; Müller, R.H. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. Int. J. Pharm., 2009, 366(1-2), 170-184.
[http://dx.doi.org/10.1016/j.ijpharm.2008.10.003] [PMID: 18992314]
[13]
des Rieux, A.; Fievez, V.; Garinot, M.; Schneider, Y-J.; Préat, V. Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. J. Control. Release, 2006, 116(1), 1-27.
[http://dx.doi.org/10.1016/j.jconrel.2006.08.013] [PMID: 17050027]
[14]
Ranpise, N.S.; Korabu, S.S.; Ghodake, V.N. Second generation lipid nanoparticles (NLC) as an oral drug carrier for delivery of lercanidipine hydrochloride. Colloids Surf. B Biointerfaces, 2014, 116, 81-87.
[http://dx.doi.org/10.1016/j.colsurfb.2013.12.012] [PMID: 24445002]
[15]
Naseri, N.; Valizadeh, H.; Zakeri-Milani, P. Solid lipid nanoparticles and nanostructured lipid carriers: structure, preparation and application. Adv. Pharm. Bull., 2015, 5(3), 305-313.
[http://dx.doi.org/10.15171/apb.2015.043] [PMID: 26504751]
[16]
McNeil-Watson, F.; Tscharnuter, W.; Miller, J. A new instrument for the measurement of very small electrophoretic mobilities using phase analysis light scattering (PALS). Colloids Surf. A Physicochem. Eng. Asp., 1998, 140(1), 53-57.
[http://dx.doi.org/10.1016/S0927-7757(97)00267-7]
[17]
Casa, D.M.; Karam, T.K. Alves, Ade.C.; Zgoda, A.A.; Khalil, N.M.; Mainardes, R.M. Bovine serum albumin nanoparticles containing amphotericin B: characterization, cytotoxicity and in vitro antifungal evaluation. J. Nanosci. Nanotechnol., 2015, 15(12), 10183-10188.
[http://dx.doi.org/10.1166/jnn.2015.11694] [PMID: 26682465]
[18]
Niamprem, P.; Srinivas, S.; Tiyaboonchai, W. Development and characterization of indomethacin-loaded mucoadhesive nanostructured lipid carriers for topical ocular delivery. Int J Appl Biol Pharm., 2018, 10(2), 91-96.
[http://dx.doi.org/10.22159/ijap.2018v10i2.24738]
[19]
Kulkarni, S.A.; Feng, S-S. Effects of particle size and surface modification on cellular uptake and biodistribution of polymeric nanoparticles for drug delivery. Pharm. Res., 2013, 30(10), 2512-2522.
[http://dx.doi.org/10.1007/s11095-012-0958-3] [PMID: 23314933]
[20]
Sadat, S.M.A.; Jahan, S.T.; Haddadi, A. Effects of Size and Surface Charge of Polymeric Nanoparticles on in vitro and in vivo Applications. J. Biomater. Nanobiotechnol., 2016, 7, 91-108.
[http://dx.doi.org/10.4236/jbnb.2016.72011]
[21]
Win, K.Y.; Feng, S-S. Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs. Biomaterials, 2005, 26(15), 2713-2722.
[http://dx.doi.org/10.1016/j.biomaterials.2004.07.050] [PMID: 15585275]
[22]
Honary, S.; Zahir, F. Effect of zeta potential on the properties of nano-drug delivery systems - a review (Part 2). Trop. J. Pharm. Res., 2013, 12(2), 265-273.
[23]
Unger, F.; Wittmar, M.; Kissel, T. Branched polyesters based on poly[vinyl-3-(dialkylamino)alkylcarbamate-co-vinyl acetate-co-vinyl alcohol]-graft-poly(d,l-lactide-co-glycolide): effects of polymer structure on cytotoxicity. Biomaterials, 2007, 28(9), 1610-1619.
[http://dx.doi.org/10.1016/j.biomaterials.2006.12.002] [PMID: 17196250]
[24]
Chanburee, S.; Tiyaboonchai, W. Mucoadhesive nanostructured lipid carriers (NLCs) as potential carriers for improving oral delivery of curcumin. Drug Dev. Ind. Pharm., 2017, 43(3), 432-440.
[http://dx.doi.org/10.1080/03639045.2016.1257020] [PMID: 27808665]
[25]
Nayak, A.P.; Tiyaboonchai, W.; Patankar, S.; Madhusudhan, B.; Souto, E.B. Curcuminoids-loaded lipid nanoparticles: novel approach towards malaria treatment. Colloids Surf. B Biointerfaces, 2010, 81(1), 263-273.
[http://dx.doi.org/10.1016/j.colsurfb.2010.07.020] [PMID: 20688493]
[26]
Müller, R.H.; Radtke, M.; Wissing, S.A. Nanostructured lipid matrices for improved microencapsulation of drugs. Int. J. Pharm., 2002, 242(1-2), 121-128.
[http://dx.doi.org/10.1016/S0378-5173(02)00180-1] [PMID: 12176234]
[27]
Müller, R.H.; Radtke, M.; Wissing, S.A. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv. Drug Deliv. Rev., 2002, 54(Suppl. 1), S131-S155.
[http://dx.doi.org/10.1016/S0169-409X(02)00118-7] [PMID: 12460720]
[28]
Churchill, D.N.; Seely, J. Nephrotoxicity associated with combined gentamicin-amphotericin B therapy. Nephron, 1977, 19(3), 176-181.
[http://dx.doi.org/10.1159/000180883] [PMID: 268496]
[29]
Bolard, J.; Seigneuret, M.; Boudet, G. Interaction between phospholipid bilayer membranes and the polyene antibiotic amphotericin B: lipid state and cholesterol content dependence. Biochim. Biophys. Acta, 1980, 599(1), 280-293.
[http://dx.doi.org/10.1016/0005-2736(80)90074-7] [PMID: 7397150]
[30]
Adams, M.L.; Kwon, G.S. Relative aggregation state and hemolytic activity of amphotericin B encapsulated by poly(ethylene oxide)-block-poly(N-hexyl-L-aspartamide)-acyl conjugate micelles: effects of acyl chain length. J. Control. Release, 2003, 87(1-3), 23-32.
[http://dx.doi.org/10.1016/S0168-3659(02)00347-4] [PMID: 12618020]
[31]
Barwicz, J.; Tancrède, P. The effect of aggregation state of amphotericin-B on its interactions with cholesterol- or ergosterol-containing phosphatidylcholine monolayers. Chem. Phys. Lipids, 1997, 85(2), 145-155.
[http://dx.doi.org/10.1016/S0009-3084(96)02652-7] [PMID: 9138890]
[32]
Zia, Q.; Khan, A.A.; Swaleha, Z.; Owais, M. Self-assembled amphotericin B-loaded polyglutamic acid nanoparticles: Preparation, characterization and in vitro potential against Candida albicans. Int. J. Nanomedicine, 2015, 10, 1769-1790.
[PMID: 25784804]
[33]
Gagoś, M.; Arczewska, M. Influence of K+ and Na+ ions on the aggregation processes of antibiotic amphotericin B: electronic absorption and FTIR spectroscopic studies. J. Phys. Chem. B, 2011, 115(12), 3185-3192.
[http://dx.doi.org/10.1021/jp110543g] [PMID: 21375349]
[34]
Huang, W.; Zhang, Z.; Han, X.; Tang, J.; Wang, J.; Dong, S.; Wang, E. Ion channel behavior of amphotericin B in sterol-free and cholesterol- or ergosterol-containing supported phosphatidylcholine bilayer model membranes investigated by electrochemistry and spectroscopy. Biophys. J., 2002, 83(6), 3245-3255.
[http://dx.doi.org/10.1016/S0006-3495(02)75326-5] [PMID: 12496093]
[35]
Bang, J-Y.; Song, C-E.; Kim, C.; Park, W-D.; Cho, K-R.; Kim, P-I.; Lee, S-R.; Chung, W-T.; Choi, K-C. Cytotoxicity of amphotericin B-incorporated polymeric micelles composed of poly(DL-lactide-co-glycolide)/dextran graft copolymer. Arch. Pharm. Res., 2008, 31(11), 1463-1469.
[http://dx.doi.org/10.1007/s12272-001-2131-0] [PMID: 19023543]
[36]
Falamarzian, A.; Lavasanifar, A. Chemical modification of hydrophobic block in poly(ethylene oxide) poly(caprolactone) based nanocarriers: effect on the solubilization and hemolytic activity of amphotericin B. Macromol. Biosci., 2010, 10(6), 648-656.
[http://dx.doi.org/10.1002/mabi.200900387] [PMID: 20352627]
[37]
Italia, J.L.; Yahya, M.M.; Singh, D.; Ravi Kumar, M.N.V. Biodegradable nanoparticles improve oral bioavailability of amphotericin B and show reduced nephrotoxicity compared to intravenous Fungizone. Pharm. Res., 2009, 26(6), 1324-1331.
[http://dx.doi.org/10.1007/s11095-009-9841-2] [PMID: 19214716]
[38]
Anderson, T.M.; Clay, M.C.; Cioffi, A.G.; Diaz, K.A.; Hisao, G.S.; Tuttle, M.D.; Nieuwkoop, A.J.; Comellas, G.; Maryum, N.; Wang, S.; Uno, B.E.; Wildeman, E.L.; Gonen, T.; Rienstra, C.M.; Burke, M.D. Amphotericin forms an extramembranous and fungicidal sterol sponge. Nat. Chem. Biol., 2014, 10(5), 400-406.
[http://dx.doi.org/10.1038/nchembio.1496] [PMID: 24681535]
[39]
Radwan, M.A.; AlQuadeib, B.T.; Šiller, L.; Wright, M.C.; Horrocks, B. Oral administration of amphotericin B nanoparticles: antifungal activity, bioavailability and toxicity in rats. Drug Deliv., 2017, 24(1), 40-50.
[http://dx.doi.org/10.1080/10717544.2016.1228715] [PMID: 28155565]
[40]
Gulati, M.; Bajad, S.; Singh, S.; Ferdous, A.J.; Singh, M. Development of liposomal amphotericin B formulation. J. Microencapsul., 1998, 15(2), 137-151.
[http://dx.doi.org/10.3109/02652049809006844] [PMID: 9532520]

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