Microdevices For Drug Delivery-2

Passive delivery devices are based on the delivery of a drug from single or multiple reservoir implant architectures. The activation and timing of release are controlled by a polymeric membrane that is designed to hermetically seal the reservoir from the surrounding delivery site. Membrane degradation is controlled by chemical or biochemical reaction between the membrane material and the environment at the specific site of implantation. Passive delivery devices depend mainly on diffusion or osmotic pressure to deliver the drug payload, making them adequate for slow, long term drug release. Therefore the application of these types of devices is limited mainly to continuous long term treatment of chronic illness in which there is no dose dependence and the drug delivery does require active feedback control or telemetric activation.

Biodegradable polymers are currently used as passive delivery systems in clinical applications. Gliadel polymer wafers have been used local delivery of chemotherapeutic drug 1, 3-bis (2-chloroethyl)-1-nitroso-urea (BCNU) [carmustine] over a period of 3 weeks to treat remaining tumor tissues after brain tumor resection. The delivery devices release the drugs in their reservoirs slowly within the body as the biodegradable polymer dissolves through hydrolysis.

Another type is a passive restorable millimeter sized device made of compression molded poly (L-lactic) acid (PLLA) reservoirs with poly (lactide-co-glycolide) membranes. Once implanted the multiple reservoir membrane degrade, releasing the drug over time. PLLA-based devices degrade slowly over a timescale of months, allowing drugs and other biological compounds, such as heparin, human growth hormone, and dextran, to be released through the membrane before the entire device degrades and is fully absorbed at the implant site. Release through the poly (lactide-co-glycolide) membranes takes place as water is absorbed into the polymer, and swelling and hydrolysis occur. Higher-molecular-weight polymers typically take longer to degrade fully, thereby making it possible to achieve pulsatile and timely compound release by incorporating a range of molecular weights for the membrane polymers.

Both the Gliadel wafer and the device designed by Grayson et al. offer first-generation modalities for polymer-based passive drug delivery from multiple reservoirs. The Gliadel wafers are limited by their low drug concentration capabilities and relatively large device dimensions, which render their use in intracranial implantation more invasive and even impractical for some medical applications. PLLA-based devices are also limited by their relatively large size. Drug depot reservoirs in these devices are unsatisfactory for long-term release of high-dose compounds, and fabrication of the device takes a long time (on the order of days) and is extremely labor intensive. Human error during fabrication can easily introduce a wide range of mechanical and chemical variations among devices, negatively affecting the performance of the device, both in vivo and in vitro. Unsatisfactory chemical reactions between BCNU and PLLA have resulted in a need to re-evaluate the choice of materials for use in polymer-based passive-delivery devices.
Both kinds of devices are capable of releasing drugs in only one physical form, either a solid powder or a liquid solution.

References:

1. Richards Grayson, A.C. et al. Multi-pulse drug delivery from a resorbable polymeric microchip device. Nat. Mater. 2, 767–772 (2003).

2. Staples, M., Daniel, K., Cima, M.J. & Langer, R. Application of micro-and nano-electromechanical devices to drug delivery. Pharm.Res. 23, 847–863 (2006).
To be continued........