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Updated: May 28, 2026
Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles
Published on: August 28, 2015
Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size
H Cabral1, Y Matsumoto, K Mizuno
1Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Japan.
Abstract:
A major goal in cancer research is to develop carriers that can deliver drugs effectively and without side effects. Liposomal and particulate carriers with diameters of ∼100 nm have been widely used to improve the distribution and tumour accumulation of cancer drugs, but so far they have only been effective for treating highly permeable tumours. Here, we compare the accumulation and effectiveness of different sizes of long-circulating, drug-loaded polymeric micelles (with diameters of 30, 50, 70 and 100 nm) in both highly and poorly permeable tumours. All the polymer micelles penetrated highly permeable tumours in mice, but only the 30 nm micelles could penetrate poorly permeable pancreatic tumours to achieve an antitumour effect. We also showed that the penetration and efficacy of the larger micelles could be enhanced by using a transforming growth factor-β inhibitor to increase the permeability of the tumours.
Insights
Smaller drug delivery nanoparticles (30 nm) effectively target poorly permeable pancreatic tumors. Larger nanoparticles (100 nm) require permeability enhancement for similar anti-tumor effects in cancer research.
Area of Science:
- Nanomedicine
- Cancer Therapeutics
- Drug Delivery Systems
Background:
- Liposomal and particulate carriers (~100 nm) improve drug distribution and tumor accumulation but are limited to highly permeable tumors.
- Developing effective drug carriers with minimal side effects is crucial for cancer research.
Purpose of the Study:
- To compare the tumor accumulation and anti-tumor effectiveness of various sizes of long-circulating, drug-loaded polymeric micelles (30, 50, 70, and 100 nm).
- To investigate the impact of tumor permeability on the efficacy of different-sized polymeric micelles.
- To explore methods for enhancing the penetration and efficacy of larger nanoparticles in poorly permeable tumors.
Main Methods:
- Synthesized and characterized drug-loaded polymeric micelles of varying sizes (30-100 nm).
- Evaluated micelle accumulation and penetration in both highly and poorly permeable tumors in mice models.
- Assessed the anti-tumor effects of different micelle sizes.
- Investigated the use of a transforming growth factor-β inhibitor to enhance tumor permeability.
Main Results:
- All tested polymeric micelle sizes penetrated highly permeable tumors.
- Only 30 nm micelles effectively penetrated poorly permeable pancreatic tumors, demonstrating significant anti-tumor effects.
- Larger micelles (50-100 nm) showed limited penetration in poorly permeable tumors.
- Co-administration with a transforming growth factor-β inhibitor improved the penetration and efficacy of larger micelles.
Conclusions:
- Nanoparticle size is a critical factor determining drug delivery and efficacy in tumors with varying permeability.
- Smaller polymeric micelles (30 nm) offer a promising strategy for targeting poorly permeable tumors, such as pancreatic cancer.
- Enhancing tumor microenvironment permeability can overcome limitations of larger drug delivery systems, broadening their therapeutic potential.
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