Article by Aron Anderson on intravitreal drug delivery. From Sept 1. Thanks to Chip_Blockus on Yahoo for finding and delivering it.
medicaldevicesonline.com D=2
Combining Local Drug Delivery and Implantable Medical Devices
September 1, 2003
By: Aron B. Anderson
Medical Device Technology
Pages | 1 | 2
Figure 3: Example of in vitro drug release from drug-eluting coatings for the intravitreal drug delivery device. This experiment shows that drug elution control and extended release duration can be achieved for months to years by varying the polymer matrix composition.
Intravitreal implant drug delivery
Diseases of the eye are a particularly good opportunity for local delivery of a drug. Several of the most serious diseases that threaten vision, including age-related macular degeneration, diabetic retinopathy, macular aedema, choroidal neovascularisation and uveitis, cause injury to the retina, the light-sensing tissue at the back of the eye. It is difficult, however, to deliver drugs via blood circulation to the back of the eye because of the blood-retinal barrier. It is also not practical to deliver drugs to the retina from the external surface of the eye, because of diffusional barriers that exist in the tissues at the front of the eye. Consequently, local delivery of a drug to the internal chamber of the eye is perceived to be the most effective route.
Apart from injection using a needle, there are no standard methods of delivering drugs to the internal (vitreous) chamber of the eye. Furthermore, there are limited currently approved methods of providing long-term delivery of a pharmaceutical to the interior of the eye. The same drug delivery matrix technology developed for stents is being used for application on the surface of an ophthalmic drug delivery implant.6 The implant can be inserted into the eye, left in place until the drug has eluted from the delivery matrix, and then retrieved. If further therapy is needed, another implant can be placed at the site; this process can be continued until the therapy is complete. Elution experiments run on the coated devices showed that a high level of drug loading and a wide range of in vitro release rates can be achieved by modification and fine-tuning of the coating formulations (Figure 3). This drug delivery/device combination is currently in preclinical testing.
Table II: The advantages of combining controlled local drug delivery with an implantable medical device over systemic delivery of a drug.
Conclusion
Implantable medical devices have limitations in terms of their efficacy or useful lifetime because of the inherent response of the body or pathogens to implants. The methodology of combining controlled local drug delivery with an implantable medical device offers several advantages over systemic delivery of a drug (see Table II). With the recent proven success of drug-eluting stents in interventional cardiology, the local drug delivery/device combination therapy is becoming an exciting new frontier in medicine with vast social and economic potential.
The drug is targeted to the intended site of action, ensuring that the tissue needing the drug receives it
There is no need to use high or toxic systemic doses to achieve sufficient local concentrations
A sustained, controlled dosing level can be maintained around the device over the necessary duration.
References
1. R.S. Hill et al., "Immunoisolation of adult porcine islets for the treatment of diabetes mellitus. The use of photopolymerizable polyethylene glycol in the conformal coating of mass-isolated porcine islets," Ann. N. Y. Acad. Sci., 831, pp. 332−343 (1997).
2. W. Casscells, "Migration of Smooth Muscle and Endothelial Cells. Critical Events in Restenosis," Circulation, 86, pp. 723-729 (1992).
3. T. Suzuki et al., "Stent-Based Delivery of Sirolimus Reduces Neointimal Formation in a Porcine Coronary Model," Circulation, 104, pp. 1188−1193 (2001).
4. J.E. Sousa et al., "Sustained Suppression of Neointimal Proliferation by Sirolimus-Eluting Stents: One-year Angiographic and Intravascular Ultrasound Follow-Up," Circulation, 104, pp. 2007−2011 (2001).
5. M.C. Morice et al., "A Randomised Comparison of a Sirolimus-Eluting Stent With a Standard Stent for Coronary Revascularisation,"N. Engl. J. Med., 346, pp. 1773−1780 (2002).
6. S. Varner et al., "Design of a Minimally Invasive Intravitreal Drug Delivery Implant," Association for Research in Vision and Ophthalmology Annual Meeting, Fort Lauderdale, Florida, USA, May 2003.
Aron B. Anderson
SurModics Inc.
Eden Prairie, Minnesota, USA |
