000060874 001__ 60874 000060874 005__ 20170504082928.0 000060874 0247_ $$2doi$$a10.1073/pnas.1322651111 000060874 0248_ $$2sideral$$a85449 000060874 037__ $$aART-2014-85449 000060874 041__ $$aeng 000060874 100__ $$aTimko, B.P. 000060874 245__ $$aNear-infrared-actuated devices for remotely controlled drug delivery 000060874 260__ $$c2014 000060874 5060_ $$aAccess copy available to the general public$$fUnrestricted 000060874 5203_ $$aA 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 on-state 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. 000060874 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000060874 590__ $$a9.674$$b2014 000060874 591__ $$aMULTIDISCIPLINARY SCIENCES$$b4 / 57 = 0.07$$c2014$$dQ1$$eT1 000060874 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000060874 700__ $$aArruebo, M. 000060874 700__ $$aShankarappa, S.A. 000060874 700__ $$aMcAlvin, J.B. 000060874 700__ $$aOkonkwo, O.S. 000060874 700__ $$aMizrahi, B. 000060874 700__ $$aStefanescu, C.F. 000060874 700__ $$aGomez, L. 000060874 700__ $$aZhu, J. 000060874 700__ $$aZhu, A. 000060874 700__ $$0(orcid)0000-0002-8701-9745$$aSantamaria, J.$$uUniversidad de Zaragoza 000060874 700__ $$aLanger, R. 000060874 700__ $$aKohane, D.S. 000060874 7102_ $$15005$$2555$$aUniversidad de Zaragoza$$bDepartamento de Ingeniería Química y Tecnologías del Medio Ambiente$$cIngeniería Química 000060874 773__ $$g111, 4 (2014), 1349-1354$$pProc. Natl. Acad. Sci.$$tProceedings of the National Academy of Sciences$$x0027-8424 000060874 8564_ $$s1351847$$uhttps://zaguan.unizar.es/record/60874/files/texto_completo.pdf$$yVersión publicada 000060874 8564_ $$s145356$$uhttps://zaguan.unizar.es/record/60874/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000060874 909CO $$ooai:zaguan.unizar.es:60874$$particulos$$pdriver 000060874 951__ $$a2017-05-04-08:24:14 000060874 980__ $$aARTICLE