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A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles
Published on: December 23, 2016
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Design, development and clinical translation of CriPec®-based core-crosslinked polymeric micelles
Cristianne J F Rijcken1, Federica De Lorenzi2, Ilaria Biancacci2
1Cristal Therapeutics, Maastricht, the Netherlands.
Advanced Drug Delivery Reviews
|November 7, 2022
Summary
CriPec® technology utilizes core-crosslinked polymeric micelles (CCPM) for enhanced nanomedicine delivery. This platform shows promising results for targeted anticancer therapy with improved efficacy and safety in preclinical and clinical studies.
Area of Science:
- Biomedical Engineering
- Materials Science
- Pharmacology
Background:
- Nanomedicines enhance drug efficacy and safety.
- Understanding nanomedicine biodistribution is crucial for optimal design.
- CriPec® technology employs specific block copolymers for nanomedicine formulation.
Purpose of the Study:
- To evaluate the biological behavior and therapeutic potential of nanomedicines based on CriPec® technology.
- To assess the pharmacokinetic properties, biodistribution, and efficacy of core-crosslinked polymeric micelles (CCPM).
- To investigate the clinical performance of CPC634, a docetaxel-loaded CCPM formulation.
Main Methods:
- Development of amphiphilic methoxy-poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide lactate] (mPEG-b-pHPMAmLacn) block copolymers.
- Self-assembly of block copolymers into core-crosslinked polymeric micelles (CCPM) for active pharmaceutical ingredient (API) entrapment.
- Preclinical imaging, pharmacokinetic studies, and in vivo efficacy assessments in animal models.
- Clinical evaluation of CPC634, including PET imaging in cancer patients.
Main Results:
- CCPM exhibited prolonged circulation, high pathological site accumulation, and low healthy tissue uptake.
- CPC634 demonstrated favorable pharmacokinetics, safety, tumor accumulation, and antitumor efficacy in preclinical models.
- Clinical trials showed good tolerability, efficacy signs, and enhanced tumor localization of CPC634 compared to docetaxel.
- PET imaging confirmed quantifiable tumor and metastasis accumulation of radiolabeled CPC634 in cancer patients.
Conclusions:
- mPEG-b-pHPMAmLacn CCPM based on CriPec® technology represent a versatile platform for targeted drug delivery.
- The technology enables tunable and sustained drug release for improved anticancer therapy.
- CriPec® technology offers a potent, broadly applicable, and well-tolerable approach for nanomedicine development.
