Nanostructures of L-ascorbic acid alkyl esters support monomeric Amphotericin B

NOCELLI, NATALIA; YENISLEIDY DE LAS MERCEDES ZULUETA DIAZ; MARINE MILLOT; MARIA LUZ COLAZO; RAQUEL VIVIANA VICO; FANANI, MARÍA LAURA

San Luis

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica; 2019

Sociedad Argentina de Biofísica

The L-ascorbic acid alkyl esters (ASCn) are lipophilic forms of vitamin C, with pharmacological interest due to their antioxidant properties and amphiphilic behavior.1,2 ASCn self-organize into micelles and form coagels when dispersed in water1. ASC12,14,16 have been proposed as enhancers of dermal permeation, so they would act by increasing drug permeation through skin. Amphotericin B (AmB) is a potent antimicrobial widely used in the treatment of different diseases3, such as Leishmania4 infestation. This drug is highly effective, but there are several important clinical limitations that lead to severe hepatic nephrotoxicity, which can cause renal insufficiency. In this work, we study the ability of the nanostructures formed by ASC12,14,16 to solubilize AmB in its monomeric and bioactive form, and address a formulation for the topical treatment of AmB. Here, a physicochemical study is exposed using particle analysis, differential scanning calorimetry and Langmuir monolayer characterization. The results obtained with ASC16 were superior in comparison with other ASCn evaluated. Our results contribute to the understanding of the physicochemical bases that make ASCn coagels a good environment for monomeric AmB, based on their electrostatic and thermodynamic properties as well as the in-plane structure of the ASCn supramolecular arrangements. This result makes this nanostructured system attractive for additional tests for the treatment of fungal and parasitic skin infections.1-Palma, S.; Manzo, R. H.; Allemandi, D.; Fratoni, L.; Lo Nostro, P. Coagels from Ascorbic Acid Derivatives. Langmuir 2002, 18 (24), 9219?9224.2-Palma, S.; Manzo, R.; Lo Nostro, P.; Allemandi, D. Nanostructures from Alkyl Vitamin C Derivatives (ASCn): Properties and Potential Platform for Drug Delivery. Int. J. Pharm. 2007, 345 (1?2), 26?34. 3-Torrado, J. J.; Espada, R.; Ballesteros, M. P.; Torrado-Santiago, S. Amphotericin B Formulations and Drug Targeting. J. Pharm. Sci. 2008, 97 (7), 2405?2425.4-Reithinger, R.; Dujardin, J.; Louzir, H. Cutaneous Leishmaniasis. Lancet Infect. Dis. 2007, 7 (6), 581?596.