A reservoir that could be remotely triggered to release a drug would enable the patient or physician to achieve on-demand, reproducible, repeated, and tunable dosing. Such a device would allow precise adjustment of dosage to desired effect, with a consequent minimization of toxicity, and could obviate repeated drug administrations or device implantations, enhancing patient compliance. It should exhibit low off-state leakage to minimize basal effects, and tunable on-state release profiles that could be adjusted from pulsatile to sustained in real time. Despite the clear clinical need for a device that meets these criteria, none has been reported to date to our knowledge. To address this deficiency, we developed an implantable reservoir capped by a nanocomposite membrane whose permeability was modulated by irradiation with a near-infrared laser. Irradiated devices could exhibit sustained onstate drug release for at least 3 h, and could reproducibly deliver short pulses over at least 10 cycles, with an on/off ratio of 30. Devices containing aspart, a fast-acting insulin analog, could achieve glycemic control after s.c. implantation in diabetic rats, with reproducible dosing controlled by the intensity and timing of irradiation over a 2-wk period. These devices can be loaded with a wide range of drug types, and therefore represent a platform technology that might be used to address a wide variety of clinical indications.gold | nanoshell | poly(n-isopropylacrylamide) | ethylcellulose | diabetes

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Cyanoacrylate glues are easily applied to wounds with good cosmetic results. However, they tend to be brittle and can induce local tissue toxicity. A series of cyanoacrylate monomers with a flexible ether linkage and varying side-chain lengths was synthesized and characterized for potential use as tissue adhesives. The effect of side-chain length on synthesis yield, physical and mechanical properties, formaldehyde generation, cytotoxicity in vitro and biocompatibility in vivo were examined. The incorporation of etheric oxygen allowed the production of flexible monomers with good adhesive strength. Monomers with longer side-chains were found to have less toxicity both in vitro and in vivo. Polymerized hexoxyethyl cyanoacrylate was more elastic than its commercially available and widely used alkyl analog 2-octyl cyanoacrylate, without compromising biocompatibility.