| Polymeric microcarrier is a new drug delivery system which has been developed rapidly in recent decades. Because of excellent small size and surface effects, microcarrier can solve those problems which exist in the delivery process of drugs or bioactive molecules effectively, such as poor stability, low solubility, limited absorption and so on. Besides, drug can be specifically transported to focus location for targeted release. A more ideal pharmaceutical preparation and delivery system were be developed for clinical disease. Gatifloxacin(GFLX) is a new antibiotic of fluoroquinolone family, which has been widely used in various infectious disease caused by sensitive bacteria such as keratitis, bronchitis, due to its excellent antibacterial activity, broad antibacterial spectrum and good organization operation. But its bioavailability is extremely low, especially used in eye and other special, sensitive physiological environment. GFLX was chosen as model drug in this paper, microspheres were prepared and in vitro drug release performance was researched to develop a novel carrier for sustained release of GFLX, thus improve drug bioavailability and reduce systemic side effects. Specific research content is as follows:(1) Molecular imprinting technology was combined with thermally-initiated precipitation polymerization to prepare molecularly imprinted poly(hydroxyethyl methacrylate) microspheres(PHEMA MIPMs). The effects of polymerization conditions such as reaction medium, initial total monomers, cross-linker and molecular imprinting on products were investigated systematically. The interaction between GFLX and HEMA in pre-solution was studied by UV-visible spectrophotometer(UV-vis), both size and morphology of final products was characterized by scanning electron microscope(SEM). Besides, the effect of molecularly imprinted technique on drug loading and release performance of microspheres was also investigated. When the total initial monomer concentration was 1 vol% and EGDMA content was 70 mol%, group of uniform PHEMA MIPMs were prepared at different GFLX/HEMA molar ratios, with diameter range from 2.06 ± 0.07 to 2.82 ± 0.20 μm. The results of drug loading and in vitro release experiments demonstrated that PHEMA MIPMs could achieve a higher GFLX loading content and a more acceptable sustained release than non-imprinted ones, which was attributed to the molecular imprinting effects. A novel drug carrier design was developed for the sustained release of GFLX, which is expected to be used in the treatment of eye disease directly.(2) Carboxymethyl chitosan(CMC) microspheres were obtained using high voltage electrostatic droplet technology, the effects of main parameters such as voltage, sampling rate, concentration of raw material solution on size distribution of microspheres were investigated by single factor method. Then, CMC microspheres were modified with oxide grapheme via laminating and blending to improve stability. Morphology and chemical structure of microspheres were characterized by SEM and FT-IR. Besides, drug loading, in vitro release performance and cell toxicity of microspheres were also studied. When the raw material solution concentration was 3.0 ~ 4.0 %(w/v), voltage was 9 k V and sampling rate was 3.0 m L/h, particles with narrow size distribution could be obtained. Through blending with GO, both stability and drug loading ability of CMC microspheres were improved clearly, a higher cumulative release content in unite time was achieved to promise a long-acting antibacterial effect. Meanwhile, CMC-GO microspheres showed good biological compatibility, which could be dispersed in gel matrix to build a novel contact lens for ocular drug delivery system. |
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