Amphiphilic albumin-based nanoparticles designed for the efficient delivery of taxanes

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 IC₅₀ 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.