| The thesis includes two parts:(1) hemocompatibility study of cyclodextrins and poly(amidoamine) dendrimers;(2) Preparation and performance of drug-loaded soft contact lenses with functional partition.I. Effects of cyclodextrins on the structure and functions of blood components in vitro(charpter two)Cyclodextrins(CDs) have been extensively used in the pharmaceutical applications by various routes. Among these routes, CDs would more or less, faster or slower, directly or inderectly enter into blood stream once which administered in vivo by the praenteral, ocular, nasal routes and so on. However, there has been not enough information on the hemocompatibility of CDs until now. This study investigated the influences of CDs(α-CD, β-CD, and γ-CD) on human blood components and functions in vitro, specifically, morphology and lysis of red blood cells(RBCs), structure and conformation of fibrinogen, complement activation, and blood coagulation. It was found that 10 mg/m L of α-, β-CDs caused abnormal RBCs morphology and serious hemolysis, while γ-CD at 10 mg/m L did not impair RBCs membrane morphology and integrity. The three CDs at up to 10 mg/m L affected the local microstructure but did not change the conformation of fibrinogen. The three CDs from 0.01 to 1 mg/m L all significantly activated the complement system and displayed a concentration-dependence. The three CDs at up to 5 mg/m L in blood plasma did not cause significantly different coagulation times from the negative control. In addition, the three CDs at up to 5 mg/m L in whole blood did not cause abnormal coagulation parameters. These results provide significant information on blood safety of the three CDs for their further biomedical and pharmaceutical applications.Ⅱ. Effects of poly(amidoamine) dendrimers(PAMAM) on the structure and function of fibrinogen(charpter three)Poly(amidoamine) dendrimers have a variety of promising biomedical applications and would inevitably enter into blood once administrated in vivo by various routes. However, the blood safety of the dendrimers has not been well clarified. Fibrinogen, as a most important blood cloting factor, which plays an important role in the blood clotting, cell response, immune response and wound treatment, et al. This study focuses on the effects of poly(amidoamine) dendrimers(G3, G4, G5, G5–OH) on the structure and functions of fibrinogen. It was found that all dendrimers induced fibrinogen structural and conformational changes, but only cationic dendrimers impaired fibrinogen polymerization ability at high concentrations. In addition, the fibrinogen time would be shortened by the induce of cationic dendrimers at 0.5-10 mg/m L, but did not relate to the generation and neutral charge of dendrimers. Therefore, the surface functional groups, generation, and concentration of the dendrimers play important roles in affecting the structure and function of the fibrinogen. These results provide a critical theoretical basis for the molecular design and clinical application of the poly(amidoamine) dendrimers.Ⅲ. Preparation and performance of drug-loaded soft contact lenses with functional partition(charpter four)Soft contact lenses(SCLs) have been widely investigated in topic ophthalmic drug delivery. However, achieving a clear optic and sustained drug delivery system based on the SCLs has been a challenge until now. In this study, we developed a drug-loaded SCLs with functional partition to probe into this issue. Briefly, commercial used PHEMA hydrogel was used as the substrate, and the ring of thin drug-PHEMA films was printed on the inner surface of the substrate. The factor of layers of drug-loaded film on the performance of SCLs was studied. We found that the drug-loaded SCLs with 1 or 2 layers of drug-loaded films demonstrated a good performance compared with commercial SCLs and a sustained and long-term diclofenac sodium delivery in vitro. That design of functional partition provides a new direction for the ocular drug delivery of soft contact lenses. |
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