Two of the most crucial topics in modern medicine are medicines administration routes and their relative pharmacokinetics inside human body. The largest part of conventional drug delivery methodologies, like absorption through the gastrointestinal tract or intravenous injection, are generally based on the non-selective distribution of the active substance in the whole body, mediated by blood circulation. With these delivery methodologies, however, most of the drug reaches non-target parts of the body. This implies that higher dosages must be provided to reach the optimal concentration in the target organ, lowering administration efficacy and amplifying drug side-effects.To overcome these problematics, advanced administration strategies based on targeted delivery have been recently developed [1]. More specifically, drugs are released in controlled amounts only in correspondence of the target organ. This approach requires a superior temporal and spatial control over release, which is challenging to achieve. A possible solution to control drug delivery timing can be the use of properly designed hydrogels. Indeed, release from these biocompatible materials can be controlled through a variety of approaches [2]. For example, smart hydrogels can be tailored to release drugs only under specific conditions of pH, temperature ... Release rate can be efficiently tuned by controlling the structure and the chemistry of the hydrogels. On the other side, a possible key to allow spatial control over release can be the use of magnetically controlled microrobots [3]. These remotely controlled devices are able to perform different tasks in-vivo, including for example cell transport [4] and medicine delivery applications [5]. For the latter, they can be covered with drug releasing materials and wirelessly guided inside human body to perform administration only in close proximity of the target organ. Moreover, magnetic field is harmless for humans, allowing a limited invasivity of the microrobots in conjunction with a great manipulation precision.In this context, we describe the realization of magnetically guidable microdevices integrating smart hydrogel layers specifically tailored to perform controlled drug release. The microdevices are obtained employing additive manufacturing, specifically microstereolithography, in combination with wet metallization [6]. This approach is highly scalable and flexible and can yield micrometric sized objects at relatively low cost. To allow magnetic actuation, a CoNiP layer is applied by mean of wet metallization on the 3D printed devices. The same technique is employed also to deposit a gold layer to make the surface biocompatible. Finally, the surface is coated with the hydrogel and drug release performances are evaluated in-vitro.Two different strategies are investigated to control the drug release from the hydrogel. In the first, an alginate hydrogel is modified with click chemistry, binding the drug to the biopolymer chains by mean of a pH cleavable bond. In this way, release takes place only when the device reaches the part of the body presenting the correct pH range. An example of possible application of this method may be drug release in well-defined zones of the gastrointestinal apparatus, which is characterized by different pH levels according to the tract considered. In the second approach, two different hydrogel couples (alginate and chitosan or alginate and poly(allylamine) hydrochloride) are sequentially deposited following a layer-by-layer technique. In this way, drug release was tuned by increasing the diffusion path in the material. This approach, even though not targeted as the first, is less complicate and more applicable to different types of drugs. Also in this case, devices are potentially usable for drug delivery inside the gastrointestinal apparatus.[1] M.W. Tibbitt et al., J. Am. Chem. Soc. 138, 704 (2016)[2] K.S. Soppimath et al., Drug Dev. Ind. Pharm. 28(8), 957 (2002)[3] J.J. Abbott, IEEE Robot. Autom. Mag. 14, 92 (2007)[4] R. Bernasconi et al., Mater. Horiz. 5, 699 (2018)[5] S. Fusco, Adv. Healthcare Mater. 2(7), 1037 (2013)[6] R. Bernasconi et al., J. Electrochem. Soc. 164(5), B3059 (2017)
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