Brian P Timko1, Daniel S Kohane. 1. Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract
BACKGROUND: Technologies in which a remote trigger is used to release drug from an implanted or injected device could enable on-demand release profiles that enhance therapeutic effectiveness or reduce systemic toxicity. A number of new materials have been developed that exhibit sensitivity to light, ultrasound, or electrical or magnetic fields. Delivery systems that incorporate these materials might be triggered externally by the patient, parent or physician to provide flexible control of dose magnitude and timing. OBJECTIVES: To review injectable or implantable systems that are candidates for translation to the clinic, or ones that have already undergone clinical trials. Also considered are applicability in pediatrics and prospects for the future of drug delivery systems. METHODS: We performed literature searches of the PubMed and Science Citation Index databases for articles in English that reported triggerable drug delivery devices, and for articles reporting related materials and concepts. RESULTS: Approaches to remotely-triggered systems that have clinical potential were identified. Ideally, these systems have been engineered to exhibit controlled on-state release kinetics, low baseline leak rates, and reproducible dosing across multiple cycles. CONCLUSIONS: Advances in remotely-triggered drug delivery have been brought about by the convergence of numerous scientific and engineering disciplines, and this convergence is likely to play an important part in the current trend to develop systems that provide more than one therapeutic modality. Preclinical systems must be carefully assessed for biocompatibility, and engineered to ensure pharmacokinetics within the therapeutic window. Future drug delivery systems may incorporate additional modalities, such as closed-loop sensing or onboard power generation, enabling more sophisticated drug delivery regimens.
BACKGROUND: Technologies in which a remote trigger is used to release drug from an implanted or injected device could enable on-demand release profiles that enhance therapeutic effectiveness or reduce systemic toxicity. A number of new materials have been developed that exhibit sensitivity to light, ultrasound, or electrical or magnetic fields. Delivery systems that incorporate these materials might be triggered externally by the patient, parent or physician to provide flexible control of dose magnitude and timing. OBJECTIVES: To review injectable or implantable systems that are candidates for translation to the clinic, or ones that have already undergone clinical trials. Also considered are applicability in pediatrics and prospects for the future of drug delivery systems. METHODS: We performed literature searches of the PubMed and Science Citation Index databases for articles in English that reported triggerable drug delivery devices, and for articles reporting related materials and concepts. RESULTS: Approaches to remotely-triggered systems that have clinical potential were identified. Ideally, these systems have been engineered to exhibit controlled on-state release kinetics, low baseline leak rates, and reproducible dosing across multiple cycles. CONCLUSIONS: Advances in remotely-triggered drug delivery have been brought about by the convergence of numerous scientific and engineering disciplines, and this convergence is likely to play an important part in the current trend to develop systems that provide more than one therapeutic modality. Preclinical systems must be carefully assessed for biocompatibility, and engineered to ensure pharmacokinetics within the therapeutic window. Future drug delivery systems may incorporate additional modalities, such as closed-loop sensing or onboard power generation, enabling more sophisticated drug delivery regimens.
Authors: Fernando Patolsky; Brian P Timko; Guihua Yu; Ying Fang; Andrew B Greytak; Gengfeng Zheng; Charles M Lieber Journal: Science Date: 2006-08-25 Impact factor: 47.728
Authors: Joseph B Ciolino; Sarah P Hudson; Ashley N Mobbs; Todd R Hoare; Naomi G Iwata; Gerald R Fink; Daniel S Kohane Journal: Invest Ophthalmol Vis Sci Date: 2011-08-09 Impact factor: 4.799
Authors: Hila Epstein-Barash; Iris Shichor; Albert H Kwon; Sherwood Hall; Michael W Lawlor; Robert Langer; Daniel S Kohane Journal: Proc Natl Acad Sci U S A Date: 2009-04-13 Impact factor: 11.205
Authors: Brian P Timko; Manuel Arruebo; Sahadev A Shankarappa; J Brian McAlvin; Obiajulu S Okonkwo; Boaz Mizrahi; Cristina F Stefanescu; Leyre Gomez; Jia Zhu; Angela Zhu; Jesus Santamaria; Robert Langer; Daniel S Kohane Journal: Proc Natl Acad Sci U S A Date: 2014-01-13 Impact factor: 11.205