Xiong Guojun, Li Shengxi, Schätzlein Andreas G, Uchegbu Ijeoma F
School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom; Nanomerics Ltd., Block Y, Northwick Park and St Marks Hospital, Watford, Harrow HA1 3UJ, United Kingdom.
Int J Pharm. 2025 Sep 15;682:125965. doi: 10.1016/j.ijpharm.2025.125965. Epub 2025 Jul 13.
In cancer chemotherapy, taxanes such as Paclitaxel (PTX), Docetaxel (DTX), and Cabazitaxel (CTX) play a pivotal role but often require surfactants and solvents for solubilization, which cause adverse effects. Plain human serum albumin (HSA) nanoparticles, such as Abraxane, utilize nab technology, which is not universally applicable to all taxanes, limiting its applicability. To address this limitation, this study introduces a novel HSA-PLA nanoparticle platform, designed to universally enhance the delivery of taxanes. This nanoplatform utilizes a thiol-maleimide reaction to form core-shell structured nanoparticles, significantly enhancing drug loading capacity and stability compared to both plain HSA nanoparticles and existing HSA-based formulations such as Abraxane. The HSA-PLA nanoparticles have shown superior drug loading, enhanced colloidal stability, and effective encapsulation of diverse hydrophobic taxanes. The HSA-PLA nanoparticles loaded with PTX, DTX, and CTX exhibited comparable sizes of 164 ± 15 nm, 124 ± 10 nm, and 148 ± 3 nm, and zeta potentials of -28.0 ± 1.7 mV, -29.3 ± 4.6 mV, and -25.5 ± 3.5 mV, respectively. Their loading capacities (LC%) were 15.1 ± 0.4 %, 13.2 ± 0.6 %, and 14.0 ± 0.8 %, with corresponding encapsulation efficiencies (EE%) of 90.3 ± 2.6 %, 78.9 ± 3.3 %, and 84.0 ± 4.5 %. The in vitro cytotoxicity tests across multiple cancer cell lines demonstrated that taxane-loaded HSA-PLA nanoparticles have low IC values (0.1-10 nM), indicating broad-spectrum anti-cancer activity. In vivo biodistribution studies further confirmed enhanced tumor deposition when compared with Abraxane. These findings suggest that HSA-PLA nanoparticles may represent a significant advancement in clinical oncology by minimizing the reliance on surfactants and overcoming the limitations of current nab technology.
在癌症化疗中，紫杉醇（PTX）、多西他赛（DTX）和卡巴他赛（CTX）等紫杉烷类药物发挥着关键作用，但通常需要表面活性剂和溶剂来增溶，这会引发不良反应。普通的人血清白蛋白（HSA）纳米颗粒，如艾日布林（Abraxane），采用了纳米白蛋白结合技术（nab技术），但该技术并非普遍适用于所有紫杉烷类药物，限制了其适用性。为解决这一局限性，本研究引入了一种新型的HSA - PLA纳米颗粒平台，旨在普遍增强紫杉烷类药物的递送。该纳米平台利用硫醇 - 马来酰亚胺反应形成核壳结构的纳米颗粒，与普通HSA纳米颗粒和现有的基于HSA的制剂（如艾日布林）相比，显著提高了载药量和稳定性。HSA - PLA纳米颗粒表现出优异的载药性能、增强的胶体稳定性以及对多种疏水性紫杉烷类药物的有效包封。负载PTX、DTX和CTX的HSA - PLA纳米颗粒的尺寸分别为164±15 nm、124±10 nm和148±3 nm，zeta电位分别为 - 28.0±1.7 mV、 - 29.3±4.6 mV和 - 25.5±3.5 mV。它们的载药量（LC%）分别为15.1±0.4%、13.2±0.6%和14.0±0.8%，相应的包封率（EE%）分别为90.3±2.6%、78.9±3.3%和84.0±4.5%。在多种癌细胞系上进行的体外细胞毒性试验表明，负载紫杉烷类药物的HSA - PLA纳米颗粒具有较低的半数抑制浓度（IC值为0.1 - 10 nM），表明其具有广谱抗癌活性。体内生物分布研究进一步证实，与艾日布林相比，其肿瘤沉积有所增强。这些发现表明，HSA - PLA纳米颗粒通过减少对表面活性剂的依赖并克服当前nab技术的局限性，可能代表了临床肿瘤学的一项重大进展。
