Nanolaminated Multilayer emulsions as a strategic delivery system for controlled release of lipophilic drugs

FIORAMONTI, SILVANA A.; RUBIOLO, AMELIA C.; SANTIAGO, LILIANA G.

Rosario

Congreso; 2da Reunión Internacional de Ciencias Farmacéuticas (RICiFa); 2012

Universidad Nacional de Rosario - Universidad Nacional de Córdoba

INTRODUCTION Oil-in-water microemulsions are important vehicles for the delivery of hydrophobic bioactive compounds into a wide variety of pharmaceutical formulations. There is an emerging technology which consists in the designing of multilayer emulsions where the lipid droplets are coated by nanolaminated self-assembled biopolymer layers, formed by electrostatic deposition [1]. These core-shell particles might have many potential applications for protection, encapsulation and sustained release of functional lipophilic drugs. This work provides experimental information about the influence of both pH and polysaccharide concentration on the stability of multilayer microemulsions produced by self-assembly between an anionic polysaccharide and a milk whey protein isolate. MATERIALS AND METHODS Whey protein isolate (WPI) was provided from Davisco (Minnesota, USA), low viscosity sodium alginate (SA) was supplied by Cargill (Buenos Aires, Argentina), and commercial sunflower oil was purchased from a local market. Primary emulsions were made by mixing sunflower oil and 2%wt. WPI solutions at pH 7 using a high-speed blender, followed by a sonication step performed by a 20 KHz ultrasonic probe. These microemulsions were then diluted by adding a sodium alginate (SA) solution and adjusting the pH to different values (7, 6, 5, 4) to form secondary emulsions, with the following final composition: 10% oil, 1% WPI, and a SA concentration range from 0.125 to 0.375%. Firstly, Transmittance and Backscattering measurements (850 nm, Turbiscan) as a function of time were made to evaluate stability of the emulsions. In parallel, the systems were observed under an optical microscope (Leica). Secondly, the emulsions were centrifuged after 24 hs, and the serum fraction was recovered to determine the concentration of both the non- adsorbed protein at the oil-water interface and the remaining polysaccharide in the aqueous phase by spectroscopic techniques [2,3]. RESULTS At a fixed concentration of 0,125% SA, microemulsions at pH 5 exhibited the lowest creaming index, becoming the most stable ones, while at the other pH values they showed phase separation due to extensive droplet flocculation, which would accelerate the destabilization of the systems by creaming. So, pH 5 was then chosen to assess the effect of SA concentration on the stability of microemulsions. Furthermore, the higher the SA concentration, the lower the creaming index the emulsions showed. This would probably be related to an increment in electrostatic repulsion between the droplets (as there might be more negatively charged polysaccharide molecules surrounding them), as well as to a gradual increase of the viscosity of the continuous phase, thereby enhancing the stability of the overall system. CONCLUSIONS This work allowed us to determine environmental conditions to design stable microemulsions, with the advantage of using natural biopolymers as wall materials to form the multilayer coatings. Besides, as microencapsulation is a novel technology not only for it could enhance and prolong the functional properties of the bioactive compounds but also because it might reduce or mask certain off-tastes, this strategy becomes an excellent candidate for the development of oral pharmaceutical formulations. ACKNOWLEDGEMENTS: Authors would like to thank financial support of CAI+D-2009 tipo II PI 57-283 project.