Abstract
Implantation of biodegradable wafers near the brain surgery site to deliver anti-cancer agents which target residual tumor cells by bypassing the blood-brain barrier has been a promising method for brain tumor treatment. However, further improvement in the prognosis is still necessary. We herein present novel materials and device technologies for drug delivery to brain tumors, i.e., a flexible, sticky, and biodegradable drug-loaded patch integrated with wireless electronics for controlled intracranial drug delivery through mild-thermic actuation. The flexible and bifacially-designed sticky/hydrophobic device allows conformal adhesion on the brain surgery site and provides spatially-controlled and temporarily-extended drug delivery to brain tumors while minimizing unintended drug leakage to the cerebrospinal fluid. Biodegradation of the entire device minimizes potential neurological side-effects. Application of the device to the mouse model confirms tumor volume suppression and improved survival rate. Demonstration in a large animal model (canine model) exhibited its potential for human application.
Highlights
DOX delivery Accelerated delivery cHeater diameter mm 20 mm 10 mm200 300 Current (A) Distance g ΔT (°C)d °C 42 °C (ΔT = 5 °C) 0 hDrug diffusion μm μm DOX stained nuclei (%) i °C j k ΔT = 5 °CΔT = 10 °C ΔT = 15 °C
We report materials and device technologies for a flexible, sticky, and biodegradable wireless electronic device integrated with a bifacially designed polymer drug reservoir, which is called as a bioresorbable electronic patch (BEP)
The integrated device, BEP, has a bifacial structure that is composed of a hydrophilic drugloaded oxidized starch (OST) film and a hydrophobic poly(lactic acid) (PLA) encapsulation film (Fig. 1a)
Summary
It should conformally adhere to the curved brain surface for local drug delivery, for facile heat transfer during mild-thermic actuation, and for prolonged drug delivery duration by minimizing unwanted drug leakage to CSF. This could be achieved by using OST which is synthesized by oxidization of starch (Supplementary Fig. 2). The strong adhesion and softness enable the conformal contact of the BEP at the tissue surface (Fig. 2c), which allows local drug delivery (Fig. 2c, inset, white circle). The BEP implanted in canine brain dissolves within 10 weeks without any debris and clinical side effects (Fig. 2g) This 10-week-period corresponds to the entire duration of drug release in vivo. The calibration curve that shows the temperature increase as a function of the magnetic field (Supplementary Fig. 13c) and/or the total eddy current (Supplementary Fig. 13d)
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