Development of nanocomposites as drug delivery vectors is a burgeoning field of research. However, the usage of such newly invented nanomatrices are often limited by the shortcomings associated with the testing of their real-life efficacy. Many drugs fail because a monolayer framework ofin vitrocell line screening method does not adequately mimic thein vivothree-dimensional microenvironments. In this direction, the study unveils the development of a continuous flow microreactor wherein the cellulose acetate nanoparticles (CANPs) with varying sizes are prepared before encapsulating them with an anticancer drug-doxorubicin (DOX). Subsequently, anin vitromicrofluidic drug delivery model has been introduced in which the HeLa cells specific to cervical cancer is treated with the DOX encapsulated CANPs-DOX@CANPs. Thereafter, the transport of the drugs from the fluidic to cellular environment, their transport inside the cell, and the real-time kinetics of the cancer cell apoptosis have been analyzed systematically to uncover the real-time efficacy and cytotoxic effects of the nanocomposite. Interestingly, experiments reveal, (i) ∼89.4% DOX loading on the nanocomposite owing to a facile electrostatic interaction, (ii) a pH-dependent controlled release of drug during the transport with the cancer cells, and (iii) cell apoptosis after the diffused inoculation of the drug. A mathematical model has been developed to emulate the drug transport from the surrounding fluid to the cancer cells. Experiments together with the mathematical model uncover that the kinetics of cancer cell death is limited by the reaction at the cell-nucleus. The microfluidic model has shown significant potential to be translated as a useful tool for the real-time and on-demandin vitroscreening of the cancer drugs.
Keywords: cancer; drug screening; kinetics; microfluidics; nanoparticles.
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