NANOMEDICINE: NANOPARTICLES OF BIODEGRADABLE POLYMERS FOR CANCER DIAGNOSIS AND TREATMENT

S. Feng
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引用次数: 8

Abstract

Nanomedicine is to apply and further develop nanotechnology to solve problems in medicine, i.e. to diagnose, treat and prevent diseases at the cellular and molecular level. This article demonstrates through a full spectrum of proof-of-concept research, from nanoparticle preparation and characterization, in vitro drug release and cytotoxicity, to in vivo pharmacokinetics and xenograft model, how nanoparticles of biodegradable polymers could provide an ideal solution for the problems encountered in the current regimen of chemotherapy. A system of vitamin E TPGS coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles is used as an example for paclitaxel formulation as a model drug. In vitro HT-29 cancer cell viability experiment demonstrated that the paclitaxel formulated in the nanoparticles could be 5.64 times more effective than Taxol® after 24 hr of treatment. In vivo pharmacokinetics showed that the drug formulated in the nanoparticles could achieve 3.9 times higher therapeutic effects judged by area-under-the curve (AUC). One shot can realize sustainable chemotherapy of 168 hr compared with 22 hr for Taxol® at a single 10 mg/kg dose. Xenograft tumor model further confirmed the advantages of the nanoparticle formulation versus Taxol®.
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纳米医学:用于癌症诊断和治疗的可生物降解聚合物纳米颗粒
纳米医学是应用和进一步发展纳米技术来解决医学问题,即在细胞和分子水平上诊断、治疗和预防疾病。本文通过全方位的概念验证研究,从纳米颗粒制备和表征,体外药物释放和细胞毒性,到体内药代动力学和异种移植模型,展示了可生物降解聚合物纳米颗粒如何为当前化疗方案中遇到的问题提供理想的解决方案。本文以维生素E TPGS包被聚乳酸-羟基乙酸(PLGA)纳米颗粒体系为例,对紫杉醇配方作为模型药物进行了研究。体外HT-29癌细胞活力实验表明,纳米颗粒中配制的紫杉醇在治疗24小时后的有效性是紫杉醇®的5.64倍。体内药代动力学结果表明,通过曲线下面积(AUC)判断,纳米颗粒配制的药物的治疗效果可提高3.9倍。紫杉醇(Taxol®)单次10 mg/kg剂量可实现持续化疗168小时,而紫杉醇(Taxol®)仅为22小时。异种移植肿瘤模型进一步证实了纳米颗粒制剂相对于紫杉醇®的优势。
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