Agwa Mona M, Marzouk Rehab Elsayed, Sabra Sally A
Department of Chemistry of Natural and Microbial Products, Pharmaceutical and Drug Industries Research Institute, National Research Centre 33 El-Behooth St, Dokki Giza 12622 Egypt
Medical Biochemistry Department, Faculty of Medicine, Helwan University Helwan Cairo Egypt.
RSC Adv. 2024 Jul 26;14(32):23520-23542. doi: 10.1039/d4ra04069d. eCollection 2024 Jul 19.
Many of the utilized drugs which already exist in the pharmaceutical sector are hydrophobic in nature. These drugs are characterized by being poorly absorbed and difficult to formulate in aqueous environments with low bioavailability, which could result in consuming high and frequent doses in order to fulfil the required therapeutic effect. As a result, there is a decisive demand to find modern alternatives to overcome all these drawbacks. Self-assembling polymeric nanomicelles (PMs) with their unique structure appear to be a fascinating choice as a pharmaceutical carrier system for improving the solubility & bioavailability of many drugs. PMs as drug carriers have many advantages including suitable size, high stability, prolonged circulation time, elevated cargo capacity and controlled therapeutic release. Otherwise, the pathological features of some diseased cells, like cancer, allow PMs with particle size <200 nm to be passively uptaken enhanced permeability and retention phenomenon (EPR). However, the passive targeting approach was proven to be insufficient in many cases. Consequently, the therapeutic efficiency of these PMs can be further reinforced by enhancing their cellular internalization incorporating targeting ligands. These targeting ligands can enhance the assemblage of loaded cargos in the intended tissues receptor-mediated endocytosis through exploiting receptors robustly expressed on the exterior of the intended tissue while minimizing their toxic effects. In this review, the up-to-date approaches of harnessing active targeting ligands to exploit certain overexpressed receptors will be summarized concerning the functionalization of the exterior of PMs for ameliorating their targeting potential in the scope of nanomedicine.
制药领域现有的许多已使用药物本质上是疏水性的。这些药物的特点是吸收差，在水性环境中难以制剂化，生物利用度低，这可能导致为达到所需治疗效果而高剂量且频繁给药。因此，迫切需要找到现代替代方法来克服所有这些缺点。具有独特结构的自组装聚合物纳米胶束（PMs）似乎是一种极具吸引力的选择，可作为改善许多药物溶解度和生物利用度的药物载体系统。PMs作为药物载体具有许多优点，包括合适的尺寸、高稳定性、延长的循环时间、提高的载药量和可控的治疗释放。此外，一些患病细胞（如癌细胞）的病理特征使粒径小于200nm的PMs能够通过增强的渗透与滞留效应（EPR）被动摄取。然而，在许多情况下，被动靶向方法被证明是不够的。因此，通过结合靶向配体增强细胞内化，可以进一步提高这些PMs的治疗效率。这些靶向配体可以通过利用在目标组织外部大量表达的受体，增强负载货物在目标组织中的聚集，通过受体介导的内吞作用，同时将其毒性作用降至最低。在这篇综述中，将总结利用活性靶向配体开发某些过表达受体的最新方法，涉及PMs外部功能化，以在纳米医学范围内改善其靶向潜力。
