Fabrication Of Biodegradable Polymer Hollow Structures

Fabrication of polymer hollow structures has aroused increasing interests due to the fascinating capacity to encapsulate and release drugs, dyes and etc. As an ideal carrier for drug release, the biocompatible, biodegradable, stimuli-responsive and targetable polymer hollow structures are strongly desired.There are three traditional dominant approaches to fabricate polymer hollow structures. The first way is the"molecular self-assembly method", i.e., to get hollow spheres, vesicles and tube structures via the self-assembly of various block copolymers. The second way is the"template method", namely to fabricate the polymer coated particles by way of the grafting/adsorbing of polymers from/on the surface of nanoparticles or micropartilces, then remove the template particles via chemical or physical methods to get the polymer hollow structures. The template method includes two routes: the surface-initiating polymerization and the"layer-by-layer"(LBL) adsorption, which have their unique advantages respectively on different conditions. The third way is the mirco-emulsion polymerization including three steps: at first the template latex particles consisting of linear carboxyl-polymers are synthesized by emulsion polymerization, then another polymer is synthesized on the surface of latex particles as the robust shell of the template particles; finally, the linear polymer cores were removed by alkaline aqueous solution while the robust hollow structures survive.Based on the mentioned developing trend and research background, we were engaged in the following studies in this dessertation. On the one hand, we adopted the"template"approach to fabricate the biodegradable polymer coated inorganic nanomaterials, then removed the template nanomaterials to get polymer hollow structures. For preparing the robust hollow spheres, the tetrafunctional lactone monomers were introduced as a crosslinking reagent to obtain the hollow spheres with network structure. On the other hand, the"self-assembly method"was employed to prepare biodegradable vesicles with controlled sizes and pH-sensitive property by the simple carboxylation with the end hydroxyl of hyperbranched polyester. Both the number of polyester generation and the concentration of the polymer solution have great effects on the size of resultant vesicles. Furthermore, the complex vesicles consisting of poly(L-lysine) and polyester were prepared via absorption of poly(L-lysine) on the surface of soft-templates (polyester vesicles). Then, the reinforced vesicles was obtained by crosslinking reaction of poly(L-lysine) with glutaraldehyde.The details are as follows:1. Preparation of Poly(β-butyrolactone) and Poly(Lactide) Hollow SpheresIn this work, we reported an effective route for preparation of Poly(β-butyrolactone) (PHB) and Poly(Lactide) (PLA) hollow spheres with tunable wall thickness, which involves the grafting polymerization of the biodegradable polymers from the surface of silica spheres followed by removing the silica templates. Nuclear magnetic resonance (NMR), thermal gravimetric analysis (TGA), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and transmission electron microscope (TEM) were used to prove the structure of the hollow spheres and the intermediates.2. Preparation of Robust Poly(ε-caprolactone) Hollow Spheres with Controlled BiodegradabilityThe in situ ring-opening"grafting from"approach was successfully applied to covalently graft poly(ε-caprolactone)(PCL) onto the surface of silica nanospheres, and the bis(ε-caprolactone-4-yl)(BCY) consisting of twoε-caprolactone rings were used as the crosslinking reagent. Then the robust poly(ε-caprolactone) (PCL) hollow spheres with tunable biodegradability were got by removing the template cores. The use of BCY not only greatly improved the stability of PCL hollow sphere but also facile controled the biodegradation velocity of the hollow spheres by addition of a certain BCY content. The solubility experiments and the biodegradation tests show that the crosslinked PCL hollow spheres are robust both in water and acetone, and are completely biodegradable with controllable biodegradation velocity according to the content of the BCY. The Rhodamine B encapsulating and releasing tests indicate that the release rate of the encapsulated guest drugs in PCL hollow spheres is controlled by osmosis and the biodegradability of crosslinking PCL hollow spheres, and the decomposition mechanism dominates the drug release when more enzymes are involved.3. Preparation of Poly(ε-caprolactone) Grafted Titanate NanotubesThe successful grafting of biodegradable poly(ε-caprolactone) (PCL) onto the surface of titanate nanotubes (TNT) was realized by the"grafting from"approach based on in-situ ring-opening polymerization ofε-caprolactone. The grafted PCL content was increased with increasing reaction time. The results indicate that the flexibility and the dispersibility of PCL-g-TNT have been improved than the bare TNT. The enzymatic degradation experiments showed that the grafted PCL can be completely decomposed within 5 days in a phosphate buffer solution (PBS) at the presence of Pseudomonas (PS) lipase. Nuclear magnetic resonance spectroscopy (NMR), thermal gravimetric analysis (TGA), Fourier-transform IR (FTIR), and transmission electron microscope (TEM) have been used to characterize the structure and the morphology of the PCL coated TNT and the intermediates.4. Fabrication of pH-Responsive and Size-Controllable Polymer Vesicles from a Commercially Available Hyperbranched PolyesterIt is interesting that the carboxyl-terminated hyperbranched biodegradable polyesters made from commercially availible BoltornTM H20, H30, H40 can be facile self-assembled into vesicles in water. Adjusting the pH value of the solution, the size of obtained vesicles can be easily controlled. the lower the pH, the bigger the vesicles. The results demonstrate the generation number and the polymer concentration significantly effect on the size of vesicles. The TEM, Static laser scattering (SLS), Dynamic laser scattering (DLS), optical microscope, 1H NMR and photon correlation spectroscopy (PCS) and Zeta potentiometer measurements were employed to characterize the structure and morphology of the vesicles.5. Facile Fabrication of Robust Polyester/Polypeptide Complex VesiclesThe polyelectrolyte complex vesicles consisting of poly (L-lysine) and polyesters were obtained by molecular self-assembly in water. To fabricate the robust complex vesicles, glutaraldehyde was employmed to crosslink the poly (L-lysine) with amine groups. The prepared vesicles were stable in strong acid, strong alkaline and even in organic solvent. Finally, the Rhodamine B was encapsulated and released in various solutions with different pH values as the simulated drug to access the drug delivery of vesicles. The resultant robust vesicles were promising in the application of drug carriers. The TEM, SEM, Laser Confocal Scanning Microscopy, optical microscope, 1H NMR and Zeta potentiometer measurements were employed to characterize the vesicles morphology and the intermediates.