Study Of Novel Hyperbranched Block Copolymer For Controlled Drug Delivery System

Nanoparticle research is currently an area of intense scientific research, due to a wide variety of potential applications. As a drug carrier, it can both entrap guest molecules in and adsorb them on the surface of the matrix, which is important for increasing drug efficiency and protecting its bioactivity. Amphiphilic biodegradable block copolymer nanoparticles play an important role in controlled release of drugs, targeting a tissue or organ, transporting biomolecules and generic drug as drug carriers. They have attracted increasing attention. In the present study, a novel poly lactic acid (PLA) functionalized hyperbranched polyglycerol (HPG) had been prepared and physicochemically characterized with the prospect of its application as a drug delivery system. Specifically, functional polymers derived from HPG were prepared that bear at the external surface PLA chains. Nanoparticles fabricated from the copolymer had nontoxic, biocompatible and biodegradable characteristics and high encapsulation capacity. Therefore, they have a promising potential as a novel drug delivery system.Ⅰ, Synthesis of copolymersThe amphiphilic copolymers were synthesized by a typical coupling reaction of PLA chains onto modified HPG in the existence of coupling agents. The number of PLA chains grafted onto HPG could be controlled by changing the feeding ratio of PLA to HPG. A series of copolymers were synthesized by using HPG and PLA with different molecular weight. The experimental results suggested that the biodegradable products have good biocompatibility.Ⅱ, Physicochemical Characterization of the copolymer nanoparticles1. The loading capacity of the copolymer nanoparticlesThe loading capacity of the copolymer nanoparticles to small hydrophobic molecules (quercetin as model drug) could reach to 26.5% under optimized conditions. Quercetin dispersed both into HPG and formed an amorphous complex with intermolecular interaction occurring within the matrices, which were favorable for increasing loading capacity.The loading capacity of the copolymer nanoparticles to biomacromolecules (BSA as model drug) could reach to 23.0% under optimized conditions. BSA dispersed both on the surface of nanoparticles by electrostatic interaction and formed a complex within the matrices by hydrophilic and hydrophobic interactions, which were favorable for increasing loading capacity.2. In vitro drug releaseIn all curves (both BSA and quercetin) a burst effect was observed followed by a slowly continuous release phase. The initial release burst corresponded to the diffusion of drugs located on the nanoparticle surfaces. The slow release profile corresponded to the release of drugs entrapped in the nanoparticles. The release time could reach 4 days for BSA and 10 days for quercetin, respectively. The copolymer nanoparticles could be used as sustained-release carriers.The release profiles could be influenced significantly by many factors (polymer composition, molecular weight, pH and drug loading capacity). The relevant relationship that existed between the characteristics of nanoparticles and the release behavior could be exploited to develop unique drug delivery system with exclusively defined release properties.In order to understand the release mechanism of nanoparticles, BSA release profiles from nanoparticles were investigated. Based on the experimental results, mathematical models were proposed to predict protein release mechanism from nanoparticle populations. The results obtained during experimental and mathematical analysis showed that two mechanisms of BSA release, namely protein diffusion and macromolecular relaxation, combined to control the release process. The degradation rate was quite low and the protein release may not be an erosion control process. The relevant relationship that existed between the characteristics of nanoparticles and the release behavior could be exploited to develop unique protein delivery system with exclusively defined release properties.