Tailoring Polymeric Micelles to Optimize Delivery to Solid Tumors

Abstract

Block copolymer micelles have shown great potential in drug delivery systems, not only for overcoming the drawbacks of small agents such as water insolubility and wide distribution in normal tissues, but also for avoiding traditional nanoparticle formulation shortcomings, including in vivo instability and fast clearance from the blood. However, for translating micellar formulations to clinical practice, it is essential to overcome the many in vivo obstacles. Surmounting these barriers strongly depends on micellar physicochemical properties, which can be further optimized by the unique physiological aspects of solid tumors such as low pH, high temperature and the presence of abnormal vessels. Herein, based on the Flory parameter and scaling theory, the fundamental mechanisms and correlations in vitro/in vivo between self assembly, drug loading and release, stability, intracellular delivery and in vivo distribution, as well as micellar composition, size and microstructural tailoring are systematically revisited. The methods for enhancing micellar performance in solid tumors were consequently proposed through well-defined core–corona structure tailoring.

Keywords::

• antibody decorating
• block copolymer
• drug delivery system
• enhanced permeability and retention
• intelligent micelles
• micelle
• physicochemical properties
• tumor microenvironment

Financial & competing interest disclosure

This work was supported, in part, by grants from the National Natural Science Foundation of China including the NSFC-81171450, Shanghai Commission of Science and Technology, Ministry of Science and Technology of China (973&863 program projects) and Pudong Commission of Science and Technology of Shanghai. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Acknowledgement

The authors thank T Okano and M Nakayama for their insightful discussion and suggestions.

Additional information

Funding

This work was supported, in part, by grants from the National Natural Science Foundation of China including the NSFC-81171450, Shanghai Commission of Science and Technology, Ministry of Science and Technology of China (973&863 program projects) and Pudong Commission of Science and Technology of Shanghai. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.