Preparation And Characterization Of Biocompatibile Core-Shell Polymeric Nanoparticles

In the past decades, nano-materials have been intensively studied in various fields. Among these materials, core-shell polymeric nanoparticles have attracted special attention due to their great potential in applications.To fabricate core-shell polymeric nanoparticles, several routes have been developed, including emulsion polymerization, template method and self-assembly etc. Besides the traditional way of preparing core-shell particles by micellization of a block or graft copolymer in a selective solvent, various micellization ways have been developed for preparing core-shell polymeric particles, for example, micellization induced by changing the environment stimuli (pH, temperature, or ionic strength), and micelliation induced by chemical reactions or complexation between the component molecules. However, core-shell polymeric nanoparticles are usually prepared at low concentrations (<5mg/mL) by the above routes, otherwise, irregular particles even precipitant can be produced, thus the preparation efficiency is very low.Driven by the requirements for its applications in bio-medicine, it has been necessary to prepare biocompatible core-shell polymeric nanoparticles. Furthermore, in order to obtain drug delivery system with controllable releasing mode, it is best to prepare stimuli-responsive core-shell polymeric nanoparticles. In addition, it is desirable to to cut down the cost by raising the preparation concentration. In this paper, protein and polysaccharide derivate, that is, Gelatin and HydroxyethylCellulose (HEC) are adopted as one component to prepare biocompatible core-shell polymeric nanoparticles. Taking advantage of "in-situ " formation of one component via "in-situ" polymerization in the presence of another component to slow down the micellization process of the components, we developed a route to prepare polymeric nanoparticles at a higher concentration, that is, "in-situ" polymerization method. And two kinds of polymeric nanoparticles were prepared via polymerizing AA in Gelatin solution and polymerizing MAA(methacrylic acid) in HEC solution, respectively.Specifically, two sections of work were carried out as follows: (l)Through the electrostatic interaction and hydrogen bonding between Gelatin and poly (acrylic acid) (PAA), the Gelatin/PAA nano-partilces were prepared at a high concentration (30mg/mL) by the in-situ polymerization of AA with Gelatin as the template. The resultant particles were comprised of Gelatin as bio-compatible shells and the insoluble complex caused by the specific interaction (electrostatic interaction and hydrogen bonding) between Gelatin and PAA as cores. Dynamic light scattering and electrophoretic light scattering techniques were used to monitor the process of the in-situ polymerization. Glutaraldehyde (GA) as a crsoolinking reagent for Gelatin was used to further lock the structure of Gelatin/PAA nano-particles. The morphologies of crosslinked particles and un-crosslinked ones were observed by SFM and TEM. Furthermore, the Gelatin/PAA particles exhibited pH sensitive: the volume of particles expanded 60 times when pH changed from 2.5 to about 7.0.(2)Through the hydrogen bonding interaction between Hydroxyethyl Cellulose (HEC) and poly (Methacrylic Acid) (PMAA), HEC/PMAApolymeric nano-particles composed of HEC as bio-compatible shells and the insoluble complex caused by hydrogen bonding interaction between HEC and PMAA as cores, were prepared via the in-situ polymerization of MAA with HEC template. N',N'-methylene bisacrylamide was used to crosslink cores of the particles in order to further in-lock the HEC/PMAA particles. Dynamic light scattering was used to trace the change on the hydrodynamic diameters with pH.