Colloids and Surfaces B: Biointerfaces 51 (2006) 54–61 Doxorubicin biocompatible O/W microemulsion stabilized by mixed surfactant containing soya phosphatidylcholine T.P. Formariz a , V.H.V. Sarmento b , A.A. Silva-Junior a , M.V. Scarpa a , C.V. Santilli b , A.G. Oliveira a,∗ a Departamento de F ´ armacos e Medicamentos, Faculdade de Ciˆ encias Farmacˆ eutico-UNESP, Rodovia Araraquara—Ja´ u km 01, 14801-902 Araraquara, SP, Brazil b Departamento de F´ ısico-Qu´ ımica, Instituto de Qu´ ımica-UNESP, Rua Francisco Degni, s/n Quitandinha, 14800-900 Araraquara, SP, Brazil Received 11 January 2006; received in revised form 5 April 2006; accepted 5 May 2006 Available online 16 May 2006 Abstract Microemulsions (ME) containing soya phosphatidylcholine (SPC)/polyoxyethylenglycerol trihydroxystearate 40 (EU)/sodium oleate (SO) as surfactant cholesterol (CHO) as oil phase and aqueous buffer were studied. Pseudo-ternary phase diagrams of the investigated systems were obtained at constant SPC/EU/SO weight ratio 3.5:3.5:3.0 by titration, in order to characterize the proportions between the components to form clear systems. The dynamic light scattering results showed that the size of the oil droplets decreases significantly with the ratio of surfactant/oil phase added to system. Depending on the composition ME system could exhibit a thixotropic behavior. The apparent viscosity increased 25- and 13-folds with cholesterol concentration for drug-free and drug-load ME, respectively. It was also verified that the octanol/aqueous buffer partition coefficient (K O/B ) of doxorubicin (DOX) was pH dependent increasing abruptly above pH 6.0. It was possible to incorporate 2.24mg/ml of DOX into ME. The incorporation of DOX in the ME systems increased the droplets size for all surfactant concentrations used in the system. The results suggest that DOX interacts with the microstructure of the ME at the studied pH increasing significantly the drug solubility. It was possible to conclude that the investigated ME can be a very promising vehicle as drug-carrier for administration of doxorubicin. © 2006 Elsevier B.V. All rights reserved. Keywords: Microemulsion; Soya phosphatidylcholine; Drug delivery; Doxorubicin 1. Introduction Colloidal systems, such as microemulsions (ME) have been investigated for drug delivery and targeting, since these sys- tems can incorporate drug compounds modifying bioavailability [1,2] and stability [3–8] and reducing side effects [9,10]. These dispersions can be defined as a mixture of at least two immis- cible liquid components stabilized by surfactant compounds, which are adsorbed at oil–water interface hindering the droplet coalescence due the favorable thermodynamic [11]. ME’s are frequently used for administration of lipophilic drugs usually dissolved in the oil phase of the O/W ME [12]. Due to its bio- compatibility and the long-term stability ME with internal phase diameter of submicron order can be used for intravenous admin- ∗ Corresponding author. Tel.: +55 16 3301 6974; fax: +55 16 3322 0073. E-mail address: oliveiag@fcfar.unesp.br (A.G. Oliveira). istration (I.V.) [13,14]. It has been described that I.V. adminis- tration of ME with droplet size in the range of 100–200 nm are largely captured by blood cells in the liver [15–18]. Because of the pharmaceutical advantages ME has been object of intensive investigations with regard to drug release [19]. In fact, depending on the composition different microstructures that can be formed, such as O/W and W/O ME and, bicontinuous structures [20–22], which can strongly affect the release of drugs [23–25]. In order to investigate the ability of ME vehicles as a drug delivery sys- tem, it is important to characterize the microstructure of ME for empty and drug-loaded. Many techniques such as light scat- tering and rheological studies associated to viscosity have been used to obtain suitable information about the properties of these systems [26–29]. Doxorubicin (DOX), 10-(4-amino-5-hydroxy-6-methyl- tetrahydropyran-2-yl)oxy-6,8,11-trihydroxy-8-(2-hydroxyace- tyl)-1-methoxy-7,8,9,10-tetrahydrotetracene 5,12-dione (CAS 0927-7765/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.colsurfb.2006.05.005