2. Academic Validation
  3. Nanomicellar Prodrug Delivery of Glucose-Paclitaxel: A Strategy to Mitigate Paclitaxel Toxicity

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

  • Int J Nanomedicine. 2025 Feb 17:20:2087-2101. doi: 10.2147/IJN.S500999.
Didi Yan 1,  Xinyue Ma 1,  Yixin Hu 1,  Guogang Zhang 1,  Beibei Hu 1,  Bo Xiang 2,  Xiaokun Cheng 1 3,  Yongshuai Jing 1,  Xi Chen 1 4
Affiliations

Affiliations

  • 1 College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, 050018, People's Republic of China.
  • 2 Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People's Republic of China.
  • 3 New Drug Research & Development Co., Ltd., North China Pharmaceutical Group Corporation, Shijiazhuang, 050015, People's Republic of China.
  • 4 Hebei Research Center of Pharmaceutical and Chemical Engineering, Shijiazhuang, 050018, People's Republic of China.
PMID: 39990288 DOI: 10.2147/IJN.S500999
Abstract

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 Vz at only 40% of that of the paclitaxel solution, while the AUC0-∞ 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.

Keywords

glucose-paclitaxel conjugate; nanomicelles; pharmacokinetics; toxicity of paclitaxel.

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