The Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 9190401, Israel.
The Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 9190401, Israel.
Adv Colloid Interface Sci. 2019 Jan;263:95-130. doi: 10.1016/j.cis.2018.11.004. Epub 2018 Nov 17.
Cancer is the second cause of death worldwide, exceeded only by cardiovascular diseases. The prevalent treatment currently used against metastatic cancer is chemotherapy. Among the most studied drugs that inhibit neoplastic cells from acquiring unlimited replicative ability (a hallmark of cancer) are the taxanes. They operate via a unique molecular mechanism affecting mitosis. In this review, we show this mechanism for one of them, paclitaxel, and for other (non-taxanes) anti-mitotic drugs. However, the use of paclitaxel is seriously limited (its bioavailability is <10%) due to several long-standing challenges: its poor water solubility (0.3 μg/mL), its being a substrate for the efflux multidrug transporter P-gp, and, in the case of oral delivery, its first-pass metabolism by certain enzymes. Adequate delivery methods are therefore required to enhance the anti-tumor activity of paclitaxel. Thus, we have also reviewed drug delivery strategies in light of the various physical, chemical, and enzymatic obstacles facing the (especially oral) delivery of drugs in general and paclitaxel in particular. Among the powerful and versatile platforms that have been developed and achieved unprecedented opportunities as drug carriers, microemulsions might have great potential for this aim. This is due to properties such as thermodynamic stability (leading to long shelf-life), increased drug solubilization, and ease of preparation and administration. In this review, we define microemulsions and nanoemulsions, analyze their pertinent properties, and review the results of several drug delivery carriers based on these systems.
癌症是全球第二大致死原因，仅次于心血管疾病。目前用于治疗转移性癌症的主要方法是化疗。在研究最多的能够抑制肿瘤细胞获得无限复制能力（癌症的一个标志）的药物中，紫杉醇是最受关注的药物之一。它们通过影响有丝分裂的独特分子机制发挥作用。在这篇综述中，我们展示了其中一种药物，紫杉醇，以及其他（非紫杉醇类）抗有丝分裂药物的这种机制。然而，由于几个长期存在的挑战，紫杉醇的使用受到了严重限制（其生物利用度<10%）：其水溶性差（0.3μg/mL），是外排多药转运蛋白 P-gp 的底物，并且在口服给药的情况下，其首先会被某些酶代谢。因此，需要适当的给药方法来提高紫杉醇的抗肿瘤活性。因此，我们还根据药物（尤其是紫杉醇）在一般给药方面所面临的各种物理、化学和酶障碍，综述了药物传递策略。在已经开发的强大且多功能的平台中，微乳液因其热力学稳定性（导致长保质期）、增加药物溶解度以及易于制备和给药等特性，可能具有很大的潜力。在这篇综述中，我们定义了微乳液和纳米乳液，分析了它们的相关特性，并综述了基于这些系统的几种药物传递载体的结果。
