Development of an in vitro Microfluidic Model to study the Enhanced Permeation and Retention(EPR) Effect for Cancer Diagnosis

S, Maneesha and Rengan, Aravind Kumar (2019) Development of an in vitro Microfluidic Model to study the Enhanced Permeation and Retention(EPR) Effect for Cancer Diagnosis. Masters thesis, Indian institute of technology Hyderabad.

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Abstract

The Enhanced Permeation and Retention (EPR) Effect is one of the mechanisms widely utilized for the delivery of drugs and nanoparticles in Cancer therapeutics and diagnosis. This effect occurs due to the hyperpermeable vasculature and poor lymphatic drainage in the tumor locales. The solid tumors have high vascular density resulting from increased angiogenesis and the blood vessels thus formed are highly irregular, dilated, tortuous and have large gaps between the endothelial junctions. These leaky endothelial gap junctions allow nanoparticles to pass through them easily resulting in selective extravasation and passive accumulation in the tumor regions. An in vitro model to study the EPR effect has been designed using microfluidics. The aim is to identify the EPR characteristics of various nanoparticles of different sizes and compositions using the microfluidic chip. This chip is capable of reducing the number of trials on the existing animal models for the preclinical investigations of the drug. The microfluidic chip closely mimicking the tumor microenvironment has been fabricated using the Lithography technique. The fluorescent metal nanoparticles such as PEG-Cu, Au nanoclusters and ZnS:Mn2+ nanoparticles have been synthesized and injected into the chip to study the kinetics as well as the selective accumulation by the tumor cells cultured in the microfluidic chip. This study further helps in rapid screening of the drugs and designing methods to enhance EPR effect which would eventually sequel effective drug delivery mechanisms for cancer diagnosis and therapeutics.

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