Alcap Delivery Devices and the Sustained Release of Difluoronethylornithine (DFNO) in Vitro and in Vivo Using Male Rats

Abstract

AbstractSprague-Dawley albino male rats (25) were divided into five groups consisting of five rats each. Polymer (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 polymer impregnated ALCAP capsules (ALCAP control). Group IV rats were administered orally 3% DFMO in drinking water. Rats in Group V served as controls. Blood samples were collected every week for nine weeks via the tail artery. The concentration of DFNO in the plasma was determined. Data obtained showed that the levels of DFMO in the serum of rats in groups I, I, and IV were 64.71 ±4.08. 219.18 ± 14.48, 16.71 ± 5.21 ug ml−1, respectively at the end of nine weeks. Body weights of the controls and DFMO treated rats were not significantly different (p<0.05). The diarrhea often noted in rats treated orally with DFHO was not observed in rats implanted with ALCAP or ALCAP capsules filled with DFMO. The results of this study suggest that: (1) polymer impregnated ALCAP ceramic implants can be used to deliver DFMO in vivo in a sustained manner for long durations of time, and (2) a ceramic system can be designed to deliver DFNO and drugs such as DFMO in a sustained manner over long durations of time in humans.