Design and implementation of an adaptive fuzzy sliding mode controller for drug delivery in treatment of vascular cancer tumours and its optimisation using genetic algorithm tool

Abstract

In this paper, the side effects of drug therapy in the process of cancer treatment are reduced by designing two optimal non-linear controllers. The related gains of the designed controllers are optimised using genetic algorithm and simultaneously are adapted by employing the Fuzzy scheduling method. The cancer dynamic model is extracted with five differential equations, including normal cells, endothelial cells, cancer cells, and the amount of two chemotherapy and anti-angiogenic drugs left in the body as the engaged state variables, while double drug injection is considered as the corresponding controlling signals of the mentioned state space. This treatment aims to reduce the tumour cells by providing a timely schedule for drug dosage. In chemotherapy, not only the cancer cells are killed but also other healthy cells will be destroyed, so the rate of drug injection is highly significant. It is shown that the simultaneous application of chemotherapy and anti-angiogenic therapy is more efficient than single chemotherapy. Two different non-linear controllers are employed and their performances are compared. Simulation results and comparison studies show that not only adding the anti-angiogenic reduce the side effects of chemotherapy but also the proposed robust controller of sliding mode provides a faster and stronger treatment in the presence of patient parametric uncertainties in an optimal way. As a result of the proposed closed-loop drug treatment, the tumour cells rapidly decrease to zero, while the normal cells remain healthy simultaneously. Also, the injection rate of the chemotherapy drug is very low after a short time and converges to zero.

Keywords: adaptive control; anti-angiogenic; cancer; cancer tumour; chemotherapy; closed loop systems; drug delivery systems; fuzzy control; fuzzy tuner; genetic algorithms; genetic optimisation tool; input-output feedback linearisation; patient treatment; radiation therapy; robust control; sliding mode control; tumours; variable structure systems.