Multifunctional approaches utilizing polymeric micelles to circumvent multidrug resistant tumors.

Abstract

The concerns impeding the success of chemotherapy in cancer is descending efficacy of drugs due to the development of multiple drug resistance (MDR). The current efforts employed to overcome MDR have failed or are limited to only preliminary in-vitro investigations. Nanotechnology is at the forefront of the drug delivery research, playing pivotal role in chemotherapy and diagnosis, thereby providing innovative approaches for the management of the disease with minimal side effects. Recently, polymeric micelles (PMs) have witnessed significant developments in cancer therapy. PMs are self-assembled colloidal particles, with a hydrophilic head and a long hydrophobic tail, which enhance the solubility, permeability and bioavailability of drugs, due to the unique features of reaching higher concentration in the biological system, above critical micellar concentration. One of the effective approaches to improve the efficacy of chemotherapy and overcome drug resistance would be to employ multifunctional approach (combination of stimuli-responsive, utilization of drug resistance modulators and combination therapy) using PMs as drug delivery systems. Actively targeted, stimuli-sensitive and multifunctional approaches involve using single and/or combination of approaches (pH-responsive, temperature regulated, reduction-sensitive, ultrasound etc.) to combat drug resistant. The review will describe PMs, types of copolymers used in PMs, preparation and characterization of PMs. A comprehensive list of PMs tested in clinical trials is discussed. Lastly, this review covers stimuli-sensitive and multifunctional approaches to overcome MDR in cancer utilizing PMs.