Thermo-Responsive Block Co-Polymers As A Drug Carriers

 

Dr. Subhas C Shit Ex-Principal Director CIPET (Ministry of Chemicals and Fertilisers, Govt.of India)

Abstract In recent years the polymers are being extensively used with stimuli triggers for delivery of drugs to the human tissues by exogenous triggers. Ths type of delivery of drugs phenomenon by a polymer in a particular location and time helps in exploiting its potential for various drug delivery in clinical practices. In this study out of many stimuli- responsive polymers only benefits of thermo responsive block copolymers are presented with the support of literature data. Introduction Polymers are being recently being utilised for delivery of drugs to the various tumors in the human body. Initially it was thought that it could be due to preferential

accumulation of certain macromolecular drugs to tumors .This preferential distribution of macrmolecular drugs to the tumors was ascribed to the defective tumor vasculature with disorganised endothelium at the tumor sight and poor lymphatic drainage system .The combination of these two phenomena was termed as the enhanced permeation and retention( EPR) effect. But at later date with the advancement of personalised medicine, this idea has become outdated. And recently stimuli responsive polymers as drug carrier has come into limelight. Stimuli –triggers used for the targeted drug drug delivery an be classified into two types :endogenous and exo-genoustriggers. Endogenous triggers (PH ,redox state and enzymic triggers)exploit the un ique characteristics of the diseased tissue and the micro environment which is completely different from normal tissue physiology.

There are a number of other parameters beyond the inner body which are termed as external stimuli(temperature, light, ultrasound, magnetic fields, etc.). Compared with the internal stimuli that make use of characteristics within a diseased tissue micro environments, the external stimuli -responsive system s could introduce contrast agents to visualise the accumulation of nano carriers in the target tissues, cells, organelles and then activate the nano carriers out of the body by exogenous triggers at the assured time.

In this text examples of such drug delivery which is spatiotemporal, by exogenous triggers are discussed for potential clinical applications.

Mechanism of release of drugs by polymers:

Exogenous stimuli-responsive polymeric nanocarriers can be engineered to release their therapeutic cargo in a programmed manner according to a specific extracellular stimuli-trigger via chemical, biochemical, or physical means .(Fig1) Evidently, exogenous triggers can be used to enhance the nano carrier activity as well as the triggered drug release to achieve diagnosis and/or therapeutic effect at disease sites.

Functionalized nanoparticles that can be triggered to enhance their activity by triggers as temperature, light, magnetic field, and US have been developed. For instance, if the drug is encapsulated within a polymeric carrier, the release can be triggered by causing structural changes such as polymer degradation, disassembly of surface layers, and charge switching. On the other hand, drugs which are covalently conjugated to the polymer backbone can be released by breaking of the polymer drug bonds. In this chapter, DDS(drug delivery systems) are discussed in order to take the advantages of externally applied stimuli temperature changes.

Fig.1 Exogenously triggered drug release by stimuli such as heat, ultrasound, magneticenergy, and light.