Plasma and cellular pharmacokinetic considerations for the development and optimization of antitumor block copolymer micelles.

INTRODUCTION: Clinical application of anticancer drugs is often limited by poor pharmacokinetic profile. The biocompatible and/or biodegradable block copolymer micelles (BCMs) can improve the pharmacokinetic behavior of drugs, thus enhancing antitumor effect. However, there are still many problems that needed to be solved before there is a wide clinical application of BCMs. AREAS COVERED: Micelles have been quickly developed recently to deliver hydrophobic antitumor drugs specifically. However, the final therapeutic effect of BCMs is often challenged by many factors in vivo from both plasma and cellular pharmacokinetic view: i) inefficient transport from administration site to tumor tissue; ii) poor penetration into tumor mass; iii) inadequate accumulation in tumor cell; and iv) insufficient intracellular/subcellular release in cells. This review emphasized on the newest methods and solutions based on the main challenges of BCMs application in vivo, and the new problems caused by these methods are also discussed. EXPERT OPINION: Different strategies and designs of BCMs can help solve problems in each key step respectively. However, overemphasis on one aspect will result in problems on others. Therefore, a comprehensive consideration is urgently needed to integrate the advantages of each strategy and overcome the disadvantages. Only with thorough understanding and scientific assessments, the desired BCMs are expected to be applied in clinical treatments.