Chytil Petr, Kostka Libor, Etrych Tomáš
Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovsky Sq. 2, 162 06 Prague, Czech Republic.
J Pers Med. 2021 Feb 10;11(2):115. doi: 10.3390/jpm11020115.
Recently, numerous polymer materials have been employed as drug carrier systems in medicinal research, and their detailed properties have been thoroughly evaluated. Water-soluble polymer carriers play a significant role between these studied polymer systems as they are advantageously applied as carriers of low-molecular-weight drugs and compounds, e.g., cytostatic agents, anti-inflammatory drugs, antimicrobial molecules, or multidrug resistance inhibitors. Covalent attachment of carried molecules using a biodegradable spacer is strongly preferred, as such design ensures the controlled release of the drug in the place of a desired pharmacological effect in a reasonable time-dependent manner. Importantly, the synthetic polymer biomaterials based on -(2-hydroxypropyl) methacrylamide (HPMA) copolymers are recognized drug carriers with unique properties that nominate them among the most serious nanomedicines candidates for human clinical trials. This review focuses on advances in the development of HPMA copolymer-based nanomedicines within the passive and active targeting into the place of desired pharmacological effect, tumors, inflammation or bacterial infection sites. Specifically, this review highlights the safety issues of HPMA polymer-based drug carriers concerning the structure of nanomedicines. The main impact consists of the improvement of targeting ability, especially concerning the enhanced and permeability retention (EPR) effect.
近年来,众多高分子材料被用作药物载体系统用于医学研究,其详细性质也得到了全面评估。水溶性高分子载体在这些已研究的高分子体系中发挥着重要作用,因为它们可作为低分子量药物和化合物(如细胞抑制剂、抗炎药、抗菌分子或多药耐药抑制剂)的载体。使用可生物降解间隔基将所载分子共价连接是非常可取的,因为这种设计能确保药物在合理的时间依赖方式下,在预期药理作用部位实现控释。重要的是,基于聚(2-羟丙基)甲基丙烯酰胺(HPMA)共聚物的合成高分子生物材料是公认的具有独特性质的药物载体,这使它们成为人类临床试验中最有潜力的纳米药物候选者之一。本综述聚焦于基于HPMA共聚物的纳米药物在被动和主动靶向至预期药理作用部位、肿瘤、炎症或细菌感染部位方面的发展进展。具体而言,本综述强调了基于HPMA聚合物的药物载体在纳米药物结构方面的安全性问题。主要影响在于靶向能力的提高,尤其是关于增强渗透滞留(EPR)效应方面。