用于抗癌药物传递的聚乳酸-羟基乙酸微粒子-阿霉素制剂

G. Çağlar, S. Yalçın, G. Gündüz, U. Gündüz
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引用次数: 2

摘要

癌症是一组正常细胞转化为能够自主生长和侵袭的细胞的疾病。在癌症的化疗控制中,药物通常是全身给药,使其达到癌细胞的毒性水平。这会对健康细胞造成严重的副作用。化疗的另一个重要问题是对细胞毒性药物的耐药性(多药耐药性)。为了解决这些问题,本研究比较了两种不同的微粒子制备方法;双乳液溶剂蒸发(SE)法将阿霉素包封在聚乳酸微球中。最合适的方法是导致更高封装效率的SE技术。考察了工艺因素对包封效率的影响,结果表明,任何阻碍药物扩散的变化都会导致微颗粒中药物含量的增加。为了评估合成的微颗粒的细胞毒性,用XTT试剂对阿霉素耐药和敏感的乳腺癌细胞株MCF-7进行了细胞增殖试验。DOX包埋的微颗粒对敏感和耐DOX的MCF-7细胞都有效。耐药癌细胞中的药物浓度增加,表明耐药性部分逆转。本研究结果将为开发用于癌症治疗的新型药物输送系统提供新的见解。
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Poly (DL-Lactic-Co-Glycolic Acid) Microparticle- Doxorubicin Formulations for Anti-cancer Drug Delivery
Cancer is a group of diseases in which normal cells are converted to cells capable of autonomous growth and invasion. In the chemotherapeutic control of cancer, drugs are usually given systemically so they reach toxic levels in cancer cells. This causes serious side effects in healthy cells. Another important problem with chemotherapy is resistance developed to cytotoxic drugs (multi drug resistance). As a possible solution to these problems, in the present study, two different microparticle fabrication methods were compared; double emulsion solvent evaporation (SE) method for encapsulation of Doxorubicin into PLGA microparticles. The most appropriate method was the SE techniquies which lead to higher encapsulation efficiencies. Processing factors were evaluated for their effects on encapsulation efficiency and results indicated that any change that hinder drug diffusion would result in increased drug content in microparticles. To asses the cytotoxicities of synthesized microparticles, cell proliferation assays were performed with XTT reagent on Doxorubicin resitant and sensitive breast cancer cell lines, MCF-7. DOX entrapped microparticles was effective on both sensitive and DOX resistant MCF-7 cells. The concentration of drug in resistant cancer cells was increased indicating a partial reversal of drug resistance. The results of this study will provide new insights to the development of new drug delivery systems for cancer therapy.
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