Polymeric micelles of fucoidan and paclitaxel for cancer therapeutic

Abstract

The aim of this study was to synthesis polymeric micelles of Fucoidan (FC) and Paclitaxel (PTX) for cancer therapeutic. To do this, amphiphilic polymer (FC-Arg- LEV-PTX) was synthesized by covalent ester and amine linkage by chemical conjugation and solvent evaporation method. The conjugated process use N-N’ - Dicyclohexylcarbodiimide (DCC) as coupling agent in the presence of 4- dimethylaminopyridine (DMAP). The micelles revealed a homogeneous spherical morphology and size was analysis by Transmission Electron Microscopy (TEM). Fourier transform infrared (FT-IR) spectroscopy was used to investigate the physicochemical properties of the polymeric micelles. High-performance liquid chromatography (HPLC) method was used to determine concentration of paclitaxel after in-vitro drug release test. Fucoidan concentration was determined by conductometric titration method. This study demonstrated amphiphilic polymer-paclitaxel conjugate (FC-Arg-LEV-PTX) could selfassemble into micelles in an aqueous system with Arg-LEV-PTX block in the core and FC in the shell. In addition, the result of in vitro release of paclitaxel and fucoidan show that its release rate was higher at lower pH 4.5 than at pH 7.4. Finding effective drug delivery system has the ability releasing two anticancer drugs as fucoidan and paclitaxel. Furthermore, the current polymeric micelles may act as drug by circulating for prolonged periods and extravasating from the vascular system, preferentially delivering drug to solid tumors Cancer nanotherapeutics has become an interesting subject of research in many biomedical fields because nanotechnology can solve several limitations of conventional drug delivery systems such as nonspecific biodistribution and targeting, lack of water solubility, poor oral bioavailability, and low therapeutic indices. Moreover, nanospheric particles have been proven as efficient drug delivery systems which are submicronsized particles (3-200 nm), devices, or systems that can be made using a variety of materials including polymers (polymeric nanoparticles, micelles, or dendrimers), lipids (liposomes) viruses (viral nanoparticles), and even organometallic compound for intravenous administration because of their comparatively long bloodstream circulation [1, 2]. At the present time, polymeric micelles seem to be one of the most advantageous carriers for the delivery of poorly water soluble drugs. Polymeric micelles are composed of distinct two domains, a drug-loading core and a hydrophilic shell amphiphilic block copolymers, containing a hydrophilic block and a hydrophobic block, are firstly revealed to construct those distinct domains in a micelle structure through spontaneous self-assembly as a result of hydrophobic interactions in aqueous solution [3]. The hydrophilic and non-ionic polymer useful as the shell-forming block