In vitro release studies of embelin-loaded PCL electrospun matrices

P.R. CORTEZ TORNELLO; G. FERESIN; A. TAPIA; G.A. ABRAHAM; T.R. CUADRADO

Viña del Mar

Taller; 3º Taller de Órganos Artificiales, Biomateriales e Ingeniería de Tejidos, OBI 2013.; 2013

Soc. Latinoamericana de Biomateriales, Organos Artificiales e Ing. de Tejidos

Electrospun polymeric matrices are being investigated for tissue engineering and controlled release applications due to their microstructure, large specific area to volume ratio, biomimetic characteristics and high porosity. The micro/nanofibers structure provides a support for cell adhesion and proliferation, and the interconnected porosity allows cell infiltration. On the other hand, the high surface area increases the drug dissolution rate, and aids in mass transfer and efficient drug release. Depending on the polymer carrier and its geometry, the kinetics release of a given pharmaceutical dosage can be designed. Poly(e-caprolactone) (PCL) is an aliphatic polyester widely used in biomedical applications, in particular in drug delivery systems because of its slow degradation rate, high drug permeability and non-toxicity. PCL-based tissue engineered scaffolds are also interesting for both hard and soft-tissue engineering applications. Embelin (2,5-dihydroxy-3-undecil-1,4-benzoquinone) is a natural benzoquinone, obtained from  Oxalis erythrorhiza Gillies. It is poorly soluble in water and shows a diversity of relevant biological activities, such as a chemopreventive effect, anti-fertility effects, in vitro cytotoxic activity against B16 and XC cell lines, and anticonvulsant, antidiabetic and antimicrobial activities. In this work, embelin-loaded PCL nanofibrous matrices were obtained by electrospinning technology. Processing parameters (needle to collector distance, applied tension, flow rate) and intrinsic solution properties (polymer and drug concentrations, solvent mixture) were optimized to produce uniform bead-free nanofibers. Matrices with different embelin content (1.5, 3 and 5% wt with respect to PCL weight) were studied (samples PCLE1.5, PCLE3, PCLE5, respectively). Morphology was observed by electron scanning microscopy (SEM). Fiber mean diameter and its distribution was determined from SEM analysis. In vitro release experiments in phosphate buffer solution (PBS, pH = 7.4) and phosphate-citrate buffer (PCB, pH = 5.0) were carried out. Drug content and release were determined by UV spectroscopy (l = 330 nm in PBS and 349 nm in PCB). Tests were conducted on an orbital shaker at a constant shaking of 150 rpm under sink conditions at 37ºC. At pre-determined time intervals, 1 ml solutions were drawn to determine the concentration of embelin, and the same volume of medium was added to the solution. SEM micrographs showed the nanofibrous morphology of the prepared systems. Mean diameters ranged from 200 to 400 nm for PCL and embelin-loaded PCL. The in vitro release profiles showed that embelin was released from the hydrophobic PCL matrix. PCLE5 exhibited an excessive initial burst release, releasing 83,5 % in 12 h in PBS and 65 % in PCB. The initial release decreased as embelin content in the matrix decreased. These results indicate that PCL nanofibers containing a poorly-soluble drug are promising as drug delivery carriers. The modeling of drug kinetics of these systems is under progress.