Drug delivery implantable systems

F Lescure, D Bichon, JM Anderson, E Doelker, ML Pelaprat, RJ Gurny. Acute histopathological response to a new biodegradable polypeptidic polymer for implantable drug delivery system. Biomed Mater Res 23 1299-1313, 1989. 

Polymeric membrane-based implantable drug delivery systems have been developed to deliver growth hormone, hormonal contraception, and leuprolide for the treatment of prostate cancer. Implanted sialic tubes loaded with lev-onorgestrel Norplant system) is used outside the United States to provide five years of sufficient sustained release of the... 

Maillefer, D., Rey-Mermet, G., Hirschi, R. A high-performance silicon micropump for an implantable drug delivery system. 12th IEEE MEMS 1999, Technical Digest, Orlando, FL, 1999. 

Pharmaceutically viable formulation applications include topical, pulmonary, depot and implantable drug delivery systems (Bhardwaj and Blanchard, 1996 Cleland andjones, 1996 Schwendeman etal., 1996 Johnsonetal., 1997 Schwendeman et al., 1997 Carrasquillo et al., 1999 Stevenson et al., 1999 Wright et al., 2001 Kikwai et al., 2004). Simple depot formulations, designed to decrease dissolution rates, have used non-aqueous conditions to achieve controlled release. Growth hormone has also been suspended in oil for depot injections (Yu et al., 1996). 

An implantable drug delivery system based on microactuation devices has been developed (36) (Fig. 4) by which doses can be controlled to an accuracy of 5 pL. One form of the invention can dispense solid drug, which of course is a more complex task, because of the... 

Figure 4 The design of the implantable drug delivery system based on shape memory alloy microactuation, showing the main reservoir, pressure chamber, and the printed circuit board (PCB) with electronics and valve system. The basic concept is to have a reservoir under constant pressure pushing liquid through a calibrated flow channel and valve system. Dimensions are 50 mm with a height of 15 mm. Source From Ref. 36.

The Norplant device has been somewhat controversial, however, due to difficulties associated with its removal. A second example of an implantable drug delivery system is Zoladex, which is an implantable biodegradable lactide/glycolide polymeric delivery system for the administration of goserelin acetate. It is available in one-month and three-month presentations and can be injected through a wide-bore needle. 

As pointed out earlier, microfluidic systems have a wide range of applications, e.g. heat exchange systems for electronic devices [28-31], medical diagnostic and analytical chemical applications [69, 70], and precision dilution systems with minimal dead volume for gas chromatography [71]. More may be anticipated as the technology matures. Current research at many laboratories has shown the need to provide flow control at extremely low levels for sensor-controlled implanted drug delivery systems [72] and portable diagnostic cards for polymerase chain reaction analysis [73]. 

Park H, Park K. Issue of implantable drug delivery systems. Pharm Res 1996 13 1770-1776. 

Advances in materials have made the development of disposable medical devices, such as needles and thermometers, as well as implantable drug delivery systems, a reality. 

Bajpai P.K. 1989. Ceramic implantable drug delivery system. TLB. A.O. 3 203-211. 

Implantable drug delivery systems are defined as longterm (>30 days) implantable products that are resorbable or removable. The resorbable implants are injectables incorporating lyophilized microspheres. The removable version is typically a subcutaneous implant, requiring minor outpatient procedures for insertion and removal. The main commercialized product in this category is Norplant , a contraceptive implant. Medtronic Corporation has two products in the implantable area that allow drug delivery into the intrathecal space (where the spinal fluid circulates). One of these products delivers baclofen for spasticity, and the other delivers anaesthetics for pain control. Both products utilize Medtronic s SynchroMed infusion pump, which can be electronically programmed to deliver any type of preset dose. 

Reynaerts D, Peirs J, Bmssel H (1997) An implantable drug-delivery system based on shape memory alloy micro-actuation. Sens Actuators A 61 455-462... 

Materials that gel in situ have recently gained attention as promising implantable drug delivery systems as well as injectable matrices for tissue engineering (76). 

The third reason why biocompatibility cannot be equated with inertness is that there are several, and indeed an increasing number, of applications which involve intentionally degradable materials. The two most widely quoted situations here are absorbable sutures and implantable drug delivery systems but many more circumstances where degradable scaffolds and matrices could form an essential component of a device are envisaged. If biocompatibility is predicated on inertness, then degradable materials cannot, by definition, be biocompatible. This clearly does not make sense and suggests that the concept of biocompatibility needs to be altered. 

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