IN VITRO RELEASE OF EMBELIN-LOADED MICROPARTICLES OBTAINED BY ELECTROHYDRODYNAMIC ATOMIZATION (EHDA)

P.R. CORTEZ TORNELLO; A. TAPIA; G.E. FERESIN; M, DZIECIUCH; T.R. CUADRADO; G.A. ABRAHAM

Rosario

Congreso; VIII Congreso Latinoamericano de Organos Artificiales, Biomateriales e Ingenieria de Tejidos (VIII COLAOB); 2014

SLABO

Polymeric particles are widely studied as drug delivery carriers that can modulate and control the delivery of therapeutic agents. Control is achieved by tailoring the structure, morphology, size, porosity and the specific polymeric matrix of the particles, as well as the drug distribution through rational particle design. Electrospraying or electrohydrodinamic atomization (EHDA) is an attractive technique with good control over particle properties such as size and morphology and can produce particle powders directly without subsequent drying or separation steps. The technique is based on the atomization of liquid via strong electrostatic forces which break up the liquid into small charged droplets that subsequently result in a homogeneous population of particles, with limited agglomeration of particles and high yields. Embelin (2,5-dihydroxy-3-undecil-1,4-benzoquinone) (C17H26O4,) is a natural benzoquinone isolated primarily from the Embelia ribes plant (Oxalidaceae). It is poorly soluble in water (0.13 mg ml-1) and it shows a diversity of relevant biological activities, such as a chemopreventive, anticonvulsant, antidiabetic and antimicrobial activities. In this present study, embelin-loaded microparticles (PCLE) were prepared by EHDA. The solutions were prepared from biodegradable polymer poly(¥å-caprolactone) (PCL, 42.5 Kg mol-1) in chloroform to 7 % wt. Embelin  was incorporated to PCL solutions (10 % wt with respect to PCL). Thermal properties were determined by differential scanning calorimetry (DSC). Morphology was examined by scanning electron microscopy (SEM), and both size and zeta potential of the particles were measured by dynamic light scattering (DLS). Embelin content was determined by ultraviolet-visible spectroscopy, and the loading efficiency was calculated from the ratio between the final and the initial embelin to polymer mass ratios.                 PCLE release behavior was measured using dialysis membranes closed at both ends, in the glass flasks containing phosphate-buffered saline at pH =7.4 and  phosphate/citrate-buffered saline at pH = 5.0 and 37 ¨¬C under stirring. SEM analysis showed that spherical particles with narrow size distribution were produced, without displaying embelin crystals on the surface. DLS analysis showed a particle average diameter of 1209.00 ¡¾ 185.50 nm and a zeta potential of -49.22 ¡¾ 2.88, indicating the high stability of PCLE microparticles. The embelin content  of PCLE microparticles was 60.81 mg of embelin per gram of sample and the encapsulation efficiency was 64.75 %. The thermal analysis indicated that the crystallinity of embelin in PCLE disappeared completely, suggesting a marked solubilization of embelin in the polymeric matrix. Furthermore, the crystallinity of PCL decreased, probably facilitating drug transport within the particles after exposure to buffers mediums.                 The release profiles of embelin from PCLE show that embelin, was released from the hydrophobic PCL particles to the aqueous solution. Two different stages were seen in the release profiles, a first step consisting of a rapid loss of embelin deposited on the surface of the particles followed by a slow- release phase, probably involving the diffusion of the active agent molecules through the PCL matrix to the aqueous solution. The initial burst release observed in both mediums lasted 12 h. However, whereas for the PBS, 80% of the embelin was released during 11 h after exposure, for the PCB this percentage was reached only after 24 h. Longer periods were required to attain full release (120 h), possibly due to the interaction of embelin and PCL, as well as poor water solubility of embelin. Drug-loaded PCL microparticles obtained by EHDA showed the ability to charge and release higher amount of drug as compared to other processing technologies available for microparticle preparation.