Synthesis Of PH-Sensitive Hollow Polymer Microspheres, Studies On Drug Carriers And Drug Release

By far, fabrication of the biocompatible and biodegradable hollow polymer microspheres with natural polymers and their derivatives has been few reported. The hollow polymer microspheres have extremely broad application prospects in medical immune and biological engineering because of high surface area, strong absorbility, biocompatibility and biodegradable. One of the most valuable application of hollow polymer microsphere is used in drug delivery and controlled release systems for drugs, enzymes, padding, pigment and catalyst. The stimuli-responsive hollow polymer microspheres have been reported in response to specific stimuli, such as pH, temperature, ion strength, magnetic field, and so on. The external environment can effectively regulate the hollow polymer microspheres to control the release of objects.In this paper, the pH-responsive hollow polymer microspheres have been prepared by the soap-free emulsion polymerization, template technique and layer-by-layer assembly. It mainly included several parts as follows.1. The mono-distributed polymeric styrene/acryl acid microspheres with polyanions were prepared by the soap-free emulsion polymerization using styrene as monomer, acrylic acid (AA) as copolymerization emulsifier, water as solvent, and K2S2O8 as initiator.2. The fabrication of pH-sensitive hollow protamine polymeric microspheres by the assembly of the natural polycation (protamine) to encapsulate the polymeric styrene/acryl acid (P(St-AA)) microspheres, etching the P(St-AA) cores with N,N-dimethylform amide (DMF) after the protamine shells were cross-linked with glutaraldehyde (GA), as illustrated in Scheme 1.3. To understand the molecular interaction mechanism of inclusion complex between hollow polymer microspheres and the medicine,5-Fluorouracil (5-Fu) and BSA-Au nanoclusters were chosen as model drugs to study their vitro drug release behavior from microspheres. Drug-loaded microspheres were prepared by incubation. The drug release properties of drug-loaded microspheres were investigated by dialysis method. The release experiment exhibited the controlled release behavior and the release were affected by pH5.0 and pH7.4 of release media, respectively. The size, the morphology and the entrapment efficiency of drug-loading microspheres were confirmed by dynamic light scattering (DLS), transmission electron microscopy (TEM) and ultraviolet absorption spectrometry (UV). The results showed that the microspheres are uniform spherical in shape, particle size between 100-250nm, with good size distribution, and high entrapment efficiency. The pH sensitive property of the microspheres may benefit the drug release in tumor cells.