Research Article
DRUG DELIVERY
First-in-Human Testing of a Wirelessly Controlled Drug Delivery Microchip
Robert Farra1,*, Norman F. Sheppard Jr.1, Laura McCabe1, Robert M. Neer2, James M. Anderson3, John T. Santini Jr.4, Michael J. Cima5 and Robert Langer6
+ Author Affiliations
1MicroCHIPS, Inc., Waltham, MA 02451, USA.
2Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
3Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
4On Demand Therapeutics Inc., Tyngsboro, MA 01879, USA.
5Department of Materials Science and Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
6Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
↵*To whom correspondence should be addressed. E-mail: rfarra@mchips.com
AbstractBack to TopThe first clinical trial of an implantable microchip-based drug delivery device is discussed. Human parathyroid hormone fragment (1–34) [hPTH(1–34)] was delivered from the device in vivo. hPTH(1–34) is the only approved anabolic osteoporosis treatment, but requires daily injections, making patient compliance an obstacle to effective treatment. Furthermore, a net increase in bone mineral density requires intermittent or pulsatile hPTH(1–34) delivery, a challenge for implantable drug delivery products. The microchip-based devices, containing discrete doses of lyophilized hPTH(1–34), were implanted in eight osteoporotic postmenopausal women for 4 months and wirelessly programmed to release doses from the device once daily for up to 20 days. A computer-based programmer, operating in the Medical Implant Communications Service band, established a bidirectional wireless communication link with the implant to program the dosing schedule and receive implant status confirming proper operation. Each woman subsequently received hPTH(1–34) injections in escalating doses. The pharmacokinetics, safety, tolerability, and bioequivalence of hPTH(1–34) were assessed. Device dosing produced similar pharmacokinetics to multiple injections and had lower coefficients of variation. Bone marker evaluation indicated that daily release from the device increased bone formation. There were no toxic or adverse events due to the device or drug, and patients stated that the implant did not affect quality of life.
Copyright © 2012, American Association for the Advancement of Science
Citation: R. Farra, N. F. Sheppard, L. McCabe, R. M. Neer, J. M. Anderson, J. T. Santini, M. J. Cima, R. Langer, First-in-Human Testing of a Wirelessly Controlled Drug Delivery Microchip. Sci. Transl. Med. 4, 122ra21 (2012).
ليست هناك تعليقات:
إرسال تعليق