Operating and compositional variables for preparation of betulinic acid nanoemulsions

Variables de operación y composición para la preparación de nanoemulsiones de ácido betulínico

A. Cavazos-Garduño¹, A.A. Ochoa Flores¹, J.C. Serrano-Niño¹, C.I. Beristain², H.S. García¹*

¹ UNIDA-Instituto Tecnológico de Veracruz, M.A. de Quevedo 2779, Veracruz, Ver. 91897, México. * Autor para la correspondencia. E-mail: hugosgg@gmail.com.

² Instituto de Ciencias Básicas, Universidad Veracruzana. Apdo. Postal 575, Xalapa, Ver. México.

Received October 18, 2013;
Accepted December 6, 2013.

Abstract

Betulinic acid is a triterpene with remarkable biological activities, including anticancer and highlights the anti -HIV activity. In recent years, nanoemulsions have been used as delivery systems to improve the bioavailability of lipophilic bioactive compounds. In this work response surface methodology (RSM) by a central composite design was employed to evaluate the effects of emulsification power, ultrasonication time, emulsifier concentration in the characteristics of betulinic acid nanoemulsions. Optimal conditions for nanoemulsions fomiation were obtained and different emulsifiers and oils as the dispersed phase were studied. The effect of pH on globule size and zeta potential of betulinic acid nanoemulsions was studied. The statistical model used for globule size effectively fitted the experimental data with a R² of 0.94. Operating conditions (power and emulsification time) and the quadratic terms, had significant effects on globule size. The optimal conditions to prepare nanoemulsions with an mean diameter of 64 nm were using 159%) emulsifier (tween 60), and an ultrasonication power of 20 W during 220 s. Nanoemulsions prepared with medium chain oil as the dispersed phase had the lowest mean globule size; however, after storage time, nanoemulsions with the mixture medium chain oil:olive oil, the globule size remained unaltered. The pH variation changed the globule surface charge, values from -30 mV were obtained, and after storage time there was no significant change in the zeta potential.

Keywords: betulinic acid, nanoemulsion, ultrasonication, globule size, delivery system.

Resumen

El ácido betulínico es un triterpeno con actividades biológicas notables; entre ellas se destacan la anticancerígena y anti-VIH. En los últimos años, las nanoemulsiones se han utilizado como sistemas de suministro para mejorar la biodisponibilidad de compuestos bioactivos lipofílicos. En este trabajo se empleó la metodología de superficie de respuesta (RSM) mediante un diseño compuesto central para evaluar los efectos de la potencia de emulsificación, el tiempo de tratamiento con ultrasonido, y la concentración de emulsificante en las características de las nanoemulsiones con ácido betulínico. Se obtuvieron condiciones óptimas de formación de las nanoemulsiones y se probaron diferentes emulsificantes y aceites como fase dispersa. Se estudió el efecto del pH en el tamaño de glóbulo y el potencial zeta de las nanoemulsiones. El modelo estadístico utilizado para el tamaño de glóbulo se ajustó con eficacia a los datos experimentales con un R² de 0.94. Las condiciones de operacion (potencia y tiempo de emulsificación), así como sus terminos cuadraticos, tuvieron efecto significativo en el tamaño de glóbulo obtenido. Las condiciones óptimas para la formación de nanoemulsiones con un diametro medio de 64 nm fueron 15% de emulsionante (tween 60), y una potencia de ultrasonicacion de 20W durante 220s. Las nanoemulsiones con el aceite de cadena media como fase dispersa tuvieron el menor tamaño de glóbulo, sin embargo, después del almacenamiento, en las nanoemulsiones con la mezcla de aceite de cadena media: aceite de oliva, el tamaño de glóbulo permaneció sin cambios. La variación del pH, cambio la carga superficial de los glóbulos, se obtuvieron valores de -30 mV, y después del tiempo de almacenamiento no hubo cambio significativo en el potencial zeta.

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Acknowledgments

The authors gratefully acknowledge the financial support of the National Council for Science and Technology of Mexico (CONACYT) through the grant 129334.

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