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Tumor-oriented mathematical models in hydrogel regulation for precise topical administration regimens.

Zhen Wang1, Bixi Ding1, Yuanpei Zhao1

  • 1Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|March 28, 2022
PubMed
Summary

This study introduces a smart hydrogel for metastatic cancer treatment, using mathematical models to personalize drug delivery based on tumor size. This approach enhances therapeutic efficacy with reduced dosage and frequency.

Keywords:
Hydrogel regulationKIAA1199 specific shRNAPersonalized synergy treatmentRedox-sensitive arginine-terminated dendrimersTumor-oriented mathematical models

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Personalized medicine requires precise drug delivery tailored to individual tumor characteristics.
  • Current cancer treatments often lack specificity, leading to suboptimal efficacy and increased side effects.

Purpose of the Study:

  • To develop a regulatory hydrogel depot for metastatic cancer treatment using mathematical models.
  • To establish a relationship between tumor characteristics and optimized administration regimens for precise drug delivery.

Main Methods:

  • Formulation of a thermo-sensitive PLGA-PEG-PLGA hydrogel incorporating doxorubicin (Dox) and KIAA1199 shRNA-loaded nanoparticles (shKIAA RPDNs).
  • Development of mathematical models to guide hydrogel administration volume and frequency based on tumor size and degradation kinetics.
  • Peritumoral injection of the hydrogel depot for sustained and localized drug delivery.

Main Results:

  • The hydrogel depot (Gel/shKIAA RPDNs/Dox) exhibited favorable distribution and degradation profiles with enhanced tumor penetration.
  • Dual-targeting therapy (Dox for DNA replication, shKIAA for KIAA1199 silencing) demonstrated synergistic anti-cancer effects.
  • Twice-daily treatment over 12 days significantly inhibited tumor proliferation and metastasis with reduced dosage.

Conclusions:

  • Controllable administration regimens based on mathematical models offer an intelligent platform for personalized metastatic cancer treatment.
  • The developed thermosensitive hydrogel system shows potential for improved therapeutic efficacy and reduced treatment burden.
  • This approach highlights the integration of material science, mathematical modeling, and targeted therapy for advanced cancer care.