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NEW aqueous carrier system for amiodarone based on liposomes with ascorbyl palmitate Benedini L.(1), Messina P.(1), Palma S. (2), Schulz P.(1) (1) Instituto de Qu¨ªmica del Sur (INQUISUR ¨C CONICET). Departamento de Qu¨ªmica, Universidad Nacional del Sur, 8000 Bah¨ªa Blanca, Argentina. (2) Unidad de Investigaci¨®n y Desarrollo en Tecnolog¨ªa Farmac¨¦utica (UNITEFA ¨C CONICET). Departamento de Farmacia. Facultad de Ciencias Qu¨ªmicas, Universidad Nacional de C¨®rdoba. Ciudad Universitaria, X5000HUA C¨®rdoba. Argentina. Introduction Amiodarone (AMI) is a class III antiarrhythmic drug which is usually administrated by intravenous infusion, showing many adverse effects. AMI-induced phospholipidosis (PLD) was suggested as the cause of its adverse effects (1). PLD is a lysosomal storage disorder characterized by the excess accumulation of phospholipids in tissues (2). Photoprotective agents may reduce the AMI effects. The use of antioxidants is theoretically a form to repair or minimize photosensitivity and other reactions produced by PLD (3). Ascorbil palmitate (Asc16) is a good antioxidant in model systems and is also effective in cells (4), retaining the radical-scavenging properties of ascorbic acid. Since its antioxidant efficiency is comparable to that of other natural reducing agents (1), Asc16 could be used to reduce or avoid AMI side effects. AMI water solubility is low and the use of surfactants and co-solvents is mandatory. These excipients can also contribute to the appearance of other kind of side effects such as negative inotropy and hypotension (5-6). The use of liposomes to carry AMI could avoid these side effects, since they can be made from natural substances which are non toxic, biodegradable and non immunogenic (7). The aim of this work is to predict the stability from liposomes formed by phospholipids, Asc16 and AMI. Results In all cases we found monomodal particle size distributions. The Asc16 addition up to 30% in liposomes did not significantly modify their size (~160 nm) increasing the negative ¦Æ values (-16.5 mV). Under experimental conditions (pH~6) Asc16 is negatively and AMI is positively charged. Therefore, when the AMI proportion is increased, the ¦Æ becomes less negative, falling down to - 6.21 mV with 20% of AMI. This can destabilize the system. The liposome neutralization by AMI addition may affect the stability of the aggregates by reducing the DLVO electrostatic repulsive barrier. The potential barrier maximum reaches 1 kBT when ¦Æ = -8.29 mV when liposomes have 10 % Asc16 and 12.7% AMI. Below this value the system could destabilize. Since all the studied liposomes were stable (even containing 20% AMI), besides DLVO forces, an additional process of stabilization exists, which was attributed to repulsive, short-range hydration forces (8), which arise from the need to dehydrate the surfaces when the particles are close enough as to fall in the primary minimum. Since this process is energetically unfavorable, the system remains stable. Conclusions The applicability of DMPC+Asc16+AMI ternary liposomes as a drug delivery system is proposed as a base in carrier systems for drugs that require an antioxidant activity to avoid or minimize AMI adverse effects. As far as we know, such systems were not previously reported. Acknowledgments This work was supported by a grant of the Universidad Nacional del Sur, and CONICET. PVM, and SDP are CONICET researchers. LB has a fellowship of CONICET. Thanks to Silvia Antollini and Marcelo Avena for their helps. References (1)- P. Martindale, The Complete Drug Reference, The Pharmaceutical Press, London. 2009; 36th ed. # Corresponding author: Luciano Benedini: Tel: 054-0291-4595101/3522; e-mail: lbenedini@uns.edu.ar.