Near-infrared-actuated devices for remotely controlled drug delivery

Timko, B.P. ; Arruebo, M. ; Shankarappa, S.A. ; McAlvin, J.B. ; Okonkwo, O.S. ; Mizrahi, B. ; Stefanescu, C.F. ; Gomez, L. ; Zhu, J. ; Zhu, A. ; Santamaria, J. (Universidad de Zaragoza) ; Langer, R. ; Kohane, D.S.

Resumen: 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 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.

Idioma: Inglés

DOI: 10.1073/pnas.1322651111

Año: 2014

Publicado en: Proceedings of the National Academy of Sciences 111, 4 (2014), 1349-1354
ISSN: 0027-8424

Factor impacto JCR: 9.674 (2014)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 4 / 57 = 0.07 (2014) - Q1 - T1

Tipo y forma: Article (Published version)

Área (Departamento): Ingeniería Química (Departamento de Ingeniería Química y Tecnologías del Medio Ambiente)