Nanomicellar Prodrug Delivery of Glucose-Paclitaxel: A Strategy to Mitigate Paclitaxel Toxicity

Background: Paclitaxel-induced blood system disorders and peripheral neuropathy impede the progress of new formulations in clinical trials. Purpose of Study: To mitigate these adverse effects by developing and validating a prodrug strategy that encapsulates a glucose-paclitaxel conjugate within nanomicelles. Material and Methods: Succinic anhydride was used as a bridge to couple C2’-paclitaxel with methyl 2’-glucopyranose and prepare a glucose-paclitaxel conjugate. Nanomicelles were prepared via solid-phase dispersion, and dynamic light scattering was used to determine their average diameter and the polydispersity index. High-performance liquid chromatography (HPLC) was employed to evaluate drug-loading capacity and encapsulation efficiency. Pharmacokinetic studies and in vivo toxicity assays were performed in Sprague-Dawley (SD) rats. Results: The nanomicellar product exhibited a spherical shape with a particle size distribution between 20– 60 nm, a PDI of 0.26 ± 0.01, and an encapsulation efficiency of 95.59 ± 1.73%. The pharmacokinetic profile of glucose-paclitaxel nanomicelles in SD rats was markedly different from that of the paclitaxel solution group. Notably, the plasma drug concentration of glucose-paclitaxel nanomicelles was significantly higher than the paclitaxel solution 15 minutes post-administration, with a V z at only 40% of that of the paclitaxel solution, while the AUC 0-∞ was five times greater than that of the paclitaxel solution. Ultimately, glucose-paclitaxel nanomicelles effectively alleviated blood system disorders and peripheral neuropathy in SD rats. Conclusion: The encapsulation of glucose-paclitaxel conjugates within nanomicelles presents a viable solution to the dose-limiting toxicities associated with paclitaxel, offering new perspectives on safety for the development of paclitaxel-based therapeutics.