本文選題：奧沙利鉑 + 脂質(zhì)體　； 參考：《遼寧醫(yī)學院》2014年碩士論文

【摘要】：目的 本實驗以實驗室自制的肝靶向?qū)蚍肿?硬脂醇半乳糖苷作為修飾材料，，制備硬脂醇半乳糖苷修飾的奧沙利鉑肝靶向脂質(zhì)體，提高奧沙利鉑的肝靶向性，降低其不良反應，以獲得最佳的治療效果。 方法 對奧沙利鉑進行處方前研究，并進行方法學驗證，建立奧沙利鉑含量測定的方法，并考察其理化性質(zhì)。采用葡聚糖凝膠微柱離心-HPLC法測定奧沙利鉑肝靶向脂質(zhì)體的包封率。以包封率作為評價指標，選擇合適的脂質(zhì)體制備方法，并以單因素考察為基礎，采用Box-Benhnken試驗設計法優(yōu)化奧沙利鉑肝靶向脂質(zhì)體的制備處方。按照篩選出的最優(yōu)處方制備肝靶向脂質(zhì)體，并考察該靶向脂質(zhì)體的形態(tài)、粒徑及包封率等理化性質(zhì)。利用體外培養(yǎng)的人肝癌細胞株SMMC-7721作為研究對象，采用細胞毒性試驗及流式細胞儀檢測細胞凋亡實驗，在細胞水平評價硬脂醇半乳糖苷修飾的奧沙利鉑肝靶向脂質(zhì)體對人肝癌細胞株SMMC-7721的抑制率及凋亡程度，初步考察奧沙利鉑肝靶向脂質(zhì)體的靶向性。 結(jié)果 本實驗建立了奧沙利鉑的含量測定方法。葡聚糖凝膠微柱離心-HPLC法適用于測定本實驗制備的奧沙利鉑肝靶向脂質(zhì)體的包封率。經(jīng)Box-Benhnken試驗設計法優(yōu)化得到的奧沙利鉑肝靶向脂質(zhì)體的最優(yōu)處方如下：磷脂質(zhì)量濃度為10.34g·L-1，脂質(zhì)與Ox質(zhì)量比為30.9∶1，脂質(zhì)與18-Gal之比為21.5∶1。按照此處方制備的奧沙利鉑肝靶向脂質(zhì)體的平均包封率為76.7%，其平均粒徑為198.4nm，電鏡下觀察該靶向脂質(zhì)體的形態(tài)近似球形。MTT細胞毒性試驗結(jié)果表明，奧沙利鉑肝靶向脂質(zhì)體對SMMC-7721細胞的抑制率明顯優(yōu)于普通脂質(zhì)體及游離奧沙利鉑的抑制率。流式細胞術實驗結(jié)果表明，在相同藥物濃度作用下，奧沙利鉑肝靶向脂質(zhì)體能誘導更多的SMMC-7721細胞凋亡。初步判定奧沙利鉑肝靶向脂質(zhì)體具有一定的肝靶向性。 結(jié)論 本實驗制備的奧沙利鉑肝靶向脂質(zhì)體，具有較高的包封率，粒徑分布均勻，可抑制肝癌細胞生長，誘導肝癌細胞凋亡，具有一定肝靶向性。
[Abstract]:PurposeIn this experiment, the liposome of oxaliplatin liposome modified by stearic galactoside was prepared by using the self-made liver targeting molecule, stearic galactoside, in order to improve the liver targeting of oxaliplatin and reduce the adverse reaction of oxaliplatin.In order to obtain the best therapeutic effect.MethodA method for the determination of oxaliplatin was established and its physical and chemical properties were investigated.The encapsulation efficiency of oxaliplatin liposomes was determined by dextran gel microcolumn centrifugation-HPLC.Taking the encapsulation efficiency as the evaluation index, the suitable preparation method of liposome was selected, and the preparation prescription of oxaliplatin liposome targeting liver was optimized by Box-Benhnken method based on single factor investigation.Liver targeting liposome was prepared according to the optimized prescription, and its physical and chemical properties such as morphology, particle size and encapsulation efficiency were investigated.Using human hepatoma cell line SMMC-7721 in vitro as the research object, cell toxicity test and flow cytometry were used to detect the apoptosis of human hepatoma cell line.To evaluate the inhibition rate and apoptosis degree of oxaliplatin liposomes modified with stearic galactoside on human hepatoma cell line SMMC-7721 and to investigate the targeting of oxaliplatin liposomes.ResultA method for the determination of oxaliplatin was established.The method of dextran gel microcolumn centrifugation and HPLC is suitable for the determination of encapsulation efficiency of oxaliplatin liposomes.The optimal formulation of oxaliplatin liposome for liver targeting was obtained by Box-Benhnken design method. The optimal formulation was as follows: the mass concentration of phospholipid was 10.34 g / L ~ (-1), the mass ratio of lipid to ox was 30.9: 1, and the ratio of lipid to 18-Gal was 21.5: 1.The average encapsulation efficiency of oxaliplatin liposome was 76.7nm and the average diameter was 198.4nm. the morphology of the liposome was approximately spherical. MTT cytotoxicity test showed that the liposome was similar in shape.The inhibition rate of oxaliplatin liposomes on SMMC-7721 cells was significantly higher than that of common liposomes and free oxaliplatin.Flow cytometry showed that oxaliplatin liposomes could induce more apoptosis of SMMC-7721 cells under the same concentration.It was preliminarily determined that oxaliplatin liposomes were liver targeting.ConclusionThe liposomes prepared in this study have high encapsulation efficiency and uniform particle size distribution, which can inhibit the growth of hepatoma cells and induce apoptosis of hepatoma cells.
【學位授予單位】：遼寧醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R943;R96

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