Acrylated vegetable oil nanoparticle as a carrier and controlled release of the anticancer drug-thymoquinone

摘要

Over the past few decades, there have been considerable interests in developing biomaterials e.g. micro- or nano-particles and micro-or nano-gels as effective drug delivery carriers. Various polymers e.g. synthetic and natural polymers, have been used in developmental of the drug carrier. Recently, in Malaysia, a group of nuclear scientist from Malaysian Nuclear Agency and University Putra Malaysia had successfully developed micro- and nano particles from natural polymer i.e. vegetable oils product using radiation-induced initiator method [1–3]. This vegetable oil product is known as acrylated vegetable oil (AVO) consists of crosslinked nanostructure when subjected to ionizing radiation sources i.e. gamma ray and electron beam was successfully utilized using the local radiation facility for the formation of micro-and nanoparticle carrier based vegetable oil product. Due to this, in this present study, the acrylated vegetable oil nanostructure was used as drug delivery system (DDS) for the incorporation of the bioactive material i.e. Thymoquinone. The work included study on the process for production of the thymoquinone-loaded AVO nanoparticle using radiation-induced method, physiochemical of the product and evaluation of its application in controlled-drug-release applications. The present study obtained varied sizes of the thymoquinone-loaded AVO micro- and nanoparticle (Table 1). Size of the thymoquinone-loaded AVO micro- and nanoparticle is in the range of nanometer and submicron as determined using dynamic light scattering (DLS) (Nanophox, Sympatec). The size of the particle was increasing when the irradiation dose increasing. As a result particle sized is in the range of 150 nm to 220 nm after irradiation at 1 to 25 kGy, respectively (Table 1). Decrease in mean diameter of the AVO micro- and nanoparticle indicates a strong shrinkage of the polymer coils resulting from the crosslinking in the AVO macromolecule structure [1–3]. This crosslinking p-nlymerization leads to the formation of smaller particles, due to the intraparticle crosslinking and to the hampered diffusion of monomer molecules to the macromolecule structure [1–5]. Furthermore, Figure 1 shows the Fourier Transform Infra Red (FTIR) (Shidmazu, Japan) chemical structure of the thymoquinone-loaded AVO micro- and nanoparticle before and after irradiation. The irradiation sensitive functional group i.e. carbon double bond (C=C, acrylic functional group) was found disappeared after the sample was irradiated at wavenumber of υ= 1410, 1620 and 1637 cm⁻¹ which revealed that the sample was undergone crosslinking. Besides that, the thymoquinone functional group i.e. dimethyl-p-benzoquina at wavenumber 1240–1250 cm⁻¹ is still presence in the AVO micro- and nanoparticle after irradiation (Figure 1). It shows that the thymoquinone was successfully incorporated in the AVO micro- and nanoparticle. The transmission electron microscopy (TEM) (Jeol, Japan) image obtained showed that, the thymoquinone-loaded AVO micro- and nanoparticle is spherical in shape as shown in Figure 2. The study also showed that the AVO micro- and nanoparticle can retain and controlled the release rate of the thymoquinone, see Figure 3. Figure 3 shows the release percentage of the thymoquinone in the 0.2 mol/L of phosphate buffer solution (PBS, pH 7.4) at 37°C as determined using Ultraviolet-visible (UV-Vis) spectrophotometer (Shidmazu, Japan). The study also revealed that such smaller particles can retain the active substance to longer period compared to that larger particle (Figure 3). This study showed that the AVO nanoparticles have successfully incorporated the thymoquinone by radiation-induced initiator method in the microemulsion system. The results obtained showed that, crosslinked nanostructure of the AVO nanoparticle contributed in the incorporation and controlling the release rate of the thymo