Sustained Delivery of Difluoromethylornithine (DFMO) by Means of Implantable Ceramic Devices

Abstract

A total of 25 Sprague-Dawley albino male rats were assigned to five groups, each group consisting of five rats. Polylactic acid-impregnated ALCAP capsules filled with 40 mg DFMO were implanted subcutaneously (sc) or intraperitoneally (ip) in group I and II rats, respectively. Rats in group III were implanted with empty ALCAP capsules (ALCAP control). Group IV rats were administered orally 3% DFMO in drinking water. Rats in group V served as control. Blood samples were collected every week for six weeks via the tail artery. The concentration of DFMO was determined by a modified ninhydrin hydrindantin method. Data obtained in this investigation showed that the levels of DFMO in the serum of rats in groups I and II were 41.87 ± 6.8 and 237.62 ± 13.3 μg/ml, respectively. Body, spleen, liver, prostate, seminal vesicles, and testicular weights of the controls and DFMO treated rats were not significantly different (p > 0.05) over the entire duration of this study. The diarrhea often noted in rats treated orally with DFMO was not observed in rats implanted with ALCAP capsules filled with DFMO. The results of this study suggest that (1) polymer-impregnated ALCAP ceramic capsules can be used to deliver DFMO in a sustained manner for long durations of time, (2) side effects associated with oral administration of DFMO can be avoided by using DFMO-filled ALCAP ceramic implants, and (3) a ceramic system can be designed to deliver DFMO and drugs such as DFMO in a sustained manner over long periods of time in humans

Key Words:

• Polylactic acid
• implantable devices
• drug delivery systems
• Alcap ceramics