Electrospun micro/nanodevices for controlled biomolecule release

摘要

Controlled biomolecule release technology represents one of the fastest advancing areas of science and engineering. For instance, in drug delivery area, such release system offers numerous advantages compared to conventional dosage drug forms including improved efficiency, reduced toxicity and controlled release profile. Current challenges in this area include biocompatiblity and biodegrability of the materials used in the system, controllablity and effectivity of the control mechanism, easiness of device fabraiction and drug loading loss as well as total cost. In this work, a simple and effective method is adopted to design and fabricate controlled release devices employing smart conmtrol mechanism. Such a technology could be further applied in pharmaceutics, biomeidical science and biotechnologies.Controlled molecule release devices in this work employ the advantage of core-shell structures. In the first design, core-shell microcapsules are developed capable of regulating the release profile of encapsulated molecules. These microcapsules uniquely contain embedded miniature actuators inside their liquid core. The internal actuators are made of stimuli-responsive smart hydrogel beads. The embedded hydrogel beads swell in response to external electric fields, regulating the internal pressure of the liquid core, and thus the diffusion rate, of the encapsulated molecules from the microcapsules. The incorporation of the actuators into the interior of the microcapsules provides an internal control variable to a conventional diffusion-based release process. The microcapsules, which behave much like micro-electro-mechanical systems (MEMS), are fabricated by a simple co-electrospray process. This fabrication technique allows integrating the hydrogel beads, forming the polymer shell, and loading the releasable molecules simultaneously in one step.The other controlled release device is developed by embedding nanofluidic biomolecule reservoirs into a polymer network of a stimuli-responsive hydrogel. The reservoirs are made of liquid core-polymer shell nanofibers using co-electrospinning technique. The mechanism of controlled release is based on buckling instability of the polymer shell under combined axial and radial compression, caused by volume changes of hydrogel responding to a specific external stimulus. The device decouples releasable biomolecules from a hydrogel polymer matrix, avoiding chemical interactions between biomolecules and hydrogel polymer chains, and thus, alleviating nontrivial chemical and biological engineering design of hydrogel formulations. Temperature-sensitive hydrogel is used as a model hydrogel.