Formulation Development Forum: Programmable, Wirelessly Controlled Microchips for Drug Delivery

Patient compliance is important when developing a drug-delivery system, particularly when treating chronic diseases that require daily administration. Researchers at the Massachusetts Institute of Technology (MIT) recently reported on an alternative to daily injections: a programmable, wirelessly controlled microchip with an implantable device that allows drugs to be released inside the body without percutaneous connections in or on the patient. An implantable microchip device also offers the potential for real-time dose schedule-tracking and for physicians to remotely adjust treatment schedules.

The MIT researchers reported positive results of a human clinical trial using such a device. The primary objective of the rial was to assess the pharmacokinetics (PK) of the released drug, teriparatide, from the implanted devices. Safety measures included evaluating the biological response to the implant and monitoring indicators of toxicity. Secondary objectives were to assess the bioactivity of the drug and to evaluate the reliability and reproducibility of releasing the drug from the device.

In the trial, human teriparatide, a parathyroid hormone fragment [hPTH(1-34)] and anabolic osteoporosis treatment, was delivered from the device in vivo. The microchip-based devices contained discrete doses of lyophilized hPTH(1-34) and were implanted in eight osteoporotic postmenopausal women for four 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 (1). The human trial began in Denmark in January 2011. The chips used in the study stored 20 doses of teriparatide, individually sealed in reservoirs capped with a thin layer of platinum and titanium that melted when a small electric current was applied, thereby releasing the drug.

The device and drug combination were found to be biocompatible with no adverse immune reaction. The resulting PK profiles from the implant were comparable to and had less variation than the PK profiles of multiple, recommended subcutaneous injections of teriparatide. The study also demonstrated that the programmable implant was able to deliver the drug at scheduled intervals. Drug delivery and evaluation in patients occurred over a one-month period and provided proof-of-concept measures of drug release and device durability that support implantable device viability for 12 months or more, according to a Feb. 16, 2012, press release of MicroCHIPS, which has licensed the technology from MIT. The MIT researchers began work on the implantable chip in the 1990s (2).

The microchip-based implants can sense biochemical changes, deliver drug therapies, and wirelessly communicate status to networked patients and clinicians. The technologies use microreservoir arrays to hermetically store and protect pharmaceuticals or sensors for extended periods of time. The microchip is controlled by microprocessors, wireless communications, or sensor feedback loops for dynamic control of drug delivery or sensing. MicroCHIPS is developing new designs of its microchip-based implant to include as many as 400 doses per device for providing daily dosing for one year or multiyear therapy for less frequent dosing regimens.

Sources

1. R. Farra et al., Sci. Transl. Med. online, DOI: 10.1126/scitranslmed.3003276. Feb. 16, 2012.

2. J. Santini, M. Cima, and R. Langer, Nature 397 (6717), 335–338 (1999).