Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy.
Molecules. 2022 Aug 25;27(17):5436. doi: 10.3390/molecules27175436.
In past decades, anticancer research has led to remarkable results despite many of the approved drugs still being characterized by high systemic toxicity mainly due to the lack of tumor selectivity and present pharmacokinetic drawbacks, including low water solubility, that negatively affect the drug circulation time and bioavailability. The stability studies, performed in mild conditions during their development or under stressing exposure to high temperature, hydrolytic medium or light source, have demonstrated the sensitivity of anticancer drugs to many parameters. For this reason, the formation of degradation products is assessed both in pharmaceutical formulations and in the environment as hospital waste. To date, numerous formulations have been developed for achieving tissue-specific drug targeting and reducing toxic side effects, as well as for improving drug stability. The development of prodrugs represents a promising strategy in targeted cancer therapy for improving the selectivity, efficacy and stability of active compounds. Recent studies show that the incorporation of anticancer drugs into vesicular systems, such as polymeric micelles or cyclodextrins, or the use of nanocarriers containing chemotherapeutics that conjugate to monoclonal antibodies can improve solubility, pharmacokinetics, cellular absorption and stability. In this study, we summarize the latest advances in knowledge regarding the development of effective highly stable anticancer drugs formulated as stable prodrugs or entrapped in nanosystems.
在过去的几十年中，尽管许多已批准的药物仍具有高全身毒性的特点，主要是由于缺乏肿瘤选择性和目前的药代动力学缺陷，包括低水溶性，这会对药物循环时间和生物利用度产生负面影响，但抗癌研究已经取得了显著的成果。在开发过程中或在高温、水解介质或光源等苛刻条件下进行的稳定性研究表明，抗癌药物对许多参数都很敏感。出于这个原因，在药物制剂中和环境中（作为医院废物）都评估了降解产物的形成。迄今为止，已经开发出许多制剂来实现组织特异性药物靶向和减少毒性副作用，以及提高药物稳定性。前药的开发是靶向癌症治疗中提高活性化合物选择性、疗效和稳定性的一种有前途的策略。最近的研究表明，将抗癌药物纳入囊泡系统，如聚合物胶束或环糊精，或使用含有与单克隆抗体结合的化疗药物的纳米载体，可以提高溶解度、药代动力学、细胞吸收和稳定性。在这项研究中，我们总结了关于开发有效且高度稳定的抗癌药物的最新进展，这些药物被制成稳定的前药或被包封在纳米系统中。
