Theory and method of temperature control for drug release in hydrogel phantom of gastric mucosa in vitro

Abstract

Unresectable tumors in the gastrointestinal tract are difficult to treat, and traditional radiotherapy combined with chemotherapy can easily induce severe side-effects due to the toxicities of anticancer drugs. Effective methods to enhance the concentration of local drug release in the narrow and hollow organs of the gastrointestinal tract are unavailable. To address this shortcoming, we propose a method to thermally trigger the release of Nile Red from temperature-sensitive liposomes (TSLs) in an in vitro hydrogel phantom of the gastric mucosa through ultrasound treatment by using a small, piezoelectric, single-crystal ultrasonic transducer with a diameter of 2.2 mm. To control the rise in temperature, we establish a model for ultrasound thermal calculation according to Helmholtz's equation, the equations of heat transfer, and the Navier–Stokes equations and validate it through an in vitro experiment. The results show that the temperature reached the melting-phase transition temperature of TSL (40–42 °C) when the duty ratio of the driving voltage of the ultrasonic transducer was 60%, and the amplitude was greater than 40 Vpp and less than 60 Vpp. Furthermore, the maximum rate of release of Nile Red was 2.9 × 10−3 mg/min when the ultrasonic transducer was activated with a driving voltage of 60 Vpp and a duty ratio of 60%. Thus, the proposed method for temperature control can be applied to improve local drug concentration in the gastrointestinal tract and reduce the number of anticancer drugs in the body.