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Effect of types of solid lipids on the physicochemical properties and self-aggregation of amphotericin B loaded nanostructured lipid carriers (NLCs)
Accepted Manuscript Title: Effect of types of solid lipids on the physicochemical properties and selfaggregation of amphotericin B loaded nanostructured lipid carriers (NLCs) Author: Pataranapa Nimtrakul, Waree Tiyaboonchai, Supaporn Lamlertthon PII: DOI: Reference:
S1818-0876(15)00217-2 http://dx.doi.org/doi: 10.1016/j.ajps.2015.11.054 AJPS 279
To appear in:
Asian Journal of Pharmaceutical Sciences
Please cite this article as: Pataranapa Nimtrakul, Waree Tiyaboonchai, Supaporn Lamlertthon, Effect of types of solid lipids on the physicochemical properties and self-aggregation of amphotericin B loaded nanostructured lipid carriers (NLCs), Asian Journal of Pharmaceutical Sciences (2015), http://dx.doi.org/doi: 10.1016/j.ajps.2015.11.054. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Effect of types of solid lipids on the physicochemical properties and selfaggregation of amphotericin B loaded nanostructured lipid carriers (NLCs) Pataranapa Nimtrakula, Waree Tiyaboonchaia,*, Supaporn Lamlertthonb a
Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand
b
Faculty of Medical Sciences, Naresuan University, Phitsanulok 65000, Thailand
*E-Mail: [email protected]
Amphotericin B (AmB), a polyene antibiotic, isone of the gold standards for the treatment of systemic fungal infections and leishmaniasis. Nowadays, only intravenous administration of AmB has been available; because of AmB is poorly absorbed from the gastrointestinal (GI) tract due to its low aqueous solubility. Currently, 2 forms of AmB are available.
The first is a mixture of AmB and sodium deoxcycholate
®
(Fungizone ) that produces severe nephrotoxicity, which may lead to kidney failure. The second is lipid-based formulations that found to reduce nephrotoxicity but these products are costly and require higher dose than Fungizone®[1-3]. Thus, the cheaper delivery system with reduce AmB toxicity is needed. In this study, we attempted to developed AmB-loaded nanostructure lipid carriers (NLCs) prepared by high pressure homogenization technique (HPH). The AmB-loaded NLCs could be successfully developed. The mean particle size was affectedby the types of solid lipids.AmB-loaded NLCs prepared with stearic acid (S), palmitic acid (P) and myristic acid (M) possessed meanparticle size of 141.57, 129.90 and 113.40 nm, respectively, All formulation showed a narrow size distribution with a polydispersity index of ~ 0.3 and zeta potential value of ~ -20 mV. The high incorporation efficiency of AmB, ~80%, was achieved. The UV–vis spectroscopy was used to investigate the aggregation state of AmB associated to NLCs. The electronic absorbance spectrum of AmB in 50% (v/v) methanol, representing the monomeric form, showed a peak ratio(326/418) of0.07, while, Fungizone®, represented the self-aggregation state of AmB, showed the peak ratio (326/418) of 2.45. The results revealed that AmB-loaded NLCs showed less aggregation state of AmB than Fungizone®. The peak ratio of AmB-loaded NLCs in formulation S, P, and M was 1.29, 1.41, and 1.80, respectively, suggesting partially aggregation state. Aggregation form of AmB-loaded NLCs was found to be dependent on the types of solid lipids; a long chain solid lipid tended to decrease the aggregation form. These results suggested that AmB-loaded NLCs could offer a reduction in nephrotoxicity compared to Fungizone®. Keywords: Nanostructure lipid carriers; Amphotericin B; Oral administration; Solid lipid; Self- aggregation
Acknowledgements
Page 1 of 2
The authors acknowledged the financial support from Naresuan University, Phitsanulok, Thailand.
References [1] Deray G. Amphotericin B nephrotoxicity. J Antimicrob Chemoth 2002; 49: 37-41. [2] Hamill R J. Amphotericin B formulations: a comparative review of efficacy and toxicity. Drugs 2013; 73:919-934. [3] Laniado-Laborin R, Cabrales-Vargas M N. Amphotericin B: side effects and toxicity.Rev Iberoam Micol 2009; 26(4): 223-227.
Fig. 1. Physicochemical properties and self-aggregationstate of AmB-loaded NLCs.
Page 2 of 2
S1818-0876(15)00217-2 http://dx.doi.org/doi: 10.1016/j.ajps.2015.11.054 AJPS 279
To appear in:
Asian Journal of Pharmaceutical Sciences
Please cite this article as: Pataranapa Nimtrakul, Waree Tiyaboonchai, Supaporn Lamlertthon, Effect of types of solid lipids on the physicochemical properties and self-aggregation of amphotericin B loaded nanostructured lipid carriers (NLCs), Asian Journal of Pharmaceutical Sciences (2015), http://dx.doi.org/doi: 10.1016/j.ajps.2015.11.054. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Effect of types of solid lipids on the physicochemical properties and selfaggregation of amphotericin B loaded nanostructured lipid carriers (NLCs) Pataranapa Nimtrakula, Waree Tiyaboonchaia,*, Supaporn Lamlertthonb a
Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand
b
Faculty of Medical Sciences, Naresuan University, Phitsanulok 65000, Thailand
*E-Mail: [email protected]
Amphotericin B (AmB), a polyene antibiotic, isone of the gold standards for the treatment of systemic fungal infections and leishmaniasis. Nowadays, only intravenous administration of AmB has been available; because of AmB is poorly absorbed from the gastrointestinal (GI) tract due to its low aqueous solubility. Currently, 2 forms of AmB are available.
The first is a mixture of AmB and sodium deoxcycholate
®
(Fungizone ) that produces severe nephrotoxicity, which may lead to kidney failure. The second is lipid-based formulations that found to reduce nephrotoxicity but these products are costly and require higher dose than Fungizone®[1-3]. Thus, the cheaper delivery system with reduce AmB toxicity is needed. In this study, we attempted to developed AmB-loaded nanostructure lipid carriers (NLCs) prepared by high pressure homogenization technique (HPH). The AmB-loaded NLCs could be successfully developed. The mean particle size was affectedby the types of solid lipids.AmB-loaded NLCs prepared with stearic acid (S), palmitic acid (P) and myristic acid (M) possessed meanparticle size of 141.57, 129.90 and 113.40 nm, respectively, All formulation showed a narrow size distribution with a polydispersity index of ~ 0.3 and zeta potential value of ~ -20 mV. The high incorporation efficiency of AmB, ~80%, was achieved. The UV–vis spectroscopy was used to investigate the aggregation state of AmB associated to NLCs. The electronic absorbance spectrum of AmB in 50% (v/v) methanol, representing the monomeric form, showed a peak ratio(326/418) of0.07, while, Fungizone®, represented the self-aggregation state of AmB, showed the peak ratio (326/418) of 2.45. The results revealed that AmB-loaded NLCs showed less aggregation state of AmB than Fungizone®. The peak ratio of AmB-loaded NLCs in formulation S, P, and M was 1.29, 1.41, and 1.80, respectively, suggesting partially aggregation state. Aggregation form of AmB-loaded NLCs was found to be dependent on the types of solid lipids; a long chain solid lipid tended to decrease the aggregation form. These results suggested that AmB-loaded NLCs could offer a reduction in nephrotoxicity compared to Fungizone®. Keywords: Nanostructure lipid carriers; Amphotericin B; Oral administration; Solid lipid; Self- aggregation
Acknowledgements
Page 1 of 2
The authors acknowledged the financial support from Naresuan University, Phitsanulok, Thailand.
References [1] Deray G. Amphotericin B nephrotoxicity. J Antimicrob Chemoth 2002; 49: 37-41. [2] Hamill R J. Amphotericin B formulations: a comparative review of efficacy and toxicity. Drugs 2013; 73:919-934. [3] Laniado-Laborin R, Cabrales-Vargas M N. Amphotericin B: side effects and toxicity.Rev Iberoam Micol 2009; 26(4): 223-227.
Fig. 1. Physicochemical properties and self-aggregationstate of AmB-loaded NLCs.
Page 2 of 2