Synthesis of Microcapsules based on Functionalized Tannins for Theragnostic Applications

Curing cancer presents a series of difficulties, with the pressing one being concerned with targeting selectively cancer cells. Equally important are aspects of the diagnosis and the monitoring of treatment efficacy. [1] This study aims at optimizing an innovative combined drug delivery and diagnosis system, i.e., a theragnosis approach, which is based on drug-loaded multifunctional tannin-based microcapsules (TMCs).[2] The envisaged system exploits the overexpressed folate receptors naturally present on cancer cells[3] for a targeted delivery mechanism via folate moieties that are linked via PEG chains to the capsule surfaces. Simple PEG moieties are surrounding these receptors in form of a stealth system lowering premature metabolic digestions. With the additional encapsulation of an anticancer drug like 5-Fluorouracil, a concomitant controlled release of an active principle at the cancer site is achieved. Diagnosis-relevance is brought into the system in form of MRI-active metal cations such as Gadolinium(III) incorporated into the shell, exploiting the metal-complexing characteristics of the shell material. The TMCs are generated by ultrasonicating a biphasic system comprising an aqueous solution of tannin or functionalized tannin, providing the eventually functionalized shell material as well as the Gd(III) salt, and an olive oil phase that functions as core material while being suitable to host the active. Resulting tannin microcapsules are characterised by means of optical and transmission electron microscopy. TMCs sizes have been determined using DLS analyses while zeta potential measurements revealed structural arrangements on the surfaces. Encapsulation efficiency and release studies were conducted for monitoring active release. Biological tests performed so far using standard capsule systems and the stained variants do not indicate any toxicity against the zebrafish embryos.