The Effects of Long-Term Sustained Delivery of Dihydrotestosterone by Poly(lactic acid) Impregnated and Noncoated Biodegradable Ceramic Devices in Male Rodents

The objectives of this investigation were to evaluate the release of dihydrotestosterone (DHT) from nonimpregnated and poly(lactic acid) (PLA) impregnated ALCAP ceramic reservoirs implanted in male rats, and to study the effects of delivered DHT on the reproductive system of male rats. A total of 120 Sprague-Dawley male albino rats were distributed equally into three groups. Two ALCAP capsules, one nonimpregnated and the other impregnated with PLA, were implanted in each rat in groups I and II. Capsules implanted in group I rats were loaded with 40 mg DHT each. Group II rats were implanted with two empty capsules (sham group), and group III animals served as un implanted controls. Eight rats from each group were euthanized at the end of the one, three, six, nine, and twelve months following the implantation of the ceramics. No significant changes in the weights of vital organs of rats were observed among any of the three different groups. Vas deferens and epididymal fluid were devoid of normal spermatozoa within three months of implanting the steroid-containing ceramics. Testes weights decreased significantly in the rats implanted with ALCAP ceramics containing DHT and the seminiferous tubules became oligospermic after one month and azoospermic after three months. The data collected in this study suggest that: (1) ALCAP ceramic cap sules are capable of delivering DHT for one year at a sustained manner; (2) DHT delivered by ALCAP capsules can be used effectively to regulate sperma togenesis in rats.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66739/2/10.1177_088391159100600201.pd

Successful antidote of multiple lethal infections using sustained delivery of difluoromethylornithine by means of ceramic drug delivery devices

The objectives of this study were (1) to cure multiple infections of trypanosorniasis in rats by the sustained release of DEMO from biodegradable tricalcium phosphate (TCP) and aluminum-calcium-phosphorous oxide (ALCAP) delivery systems, and (2) to determine if the side effects associated with oral administration of DEMO can be avoided by using TCP and ALCAP capsules. Sixty-eight SD male albino rats (235-270g) were divided randomly into five groups. Each rat in group I (n = 16) was implanted subcutaneously (s.c.) with four TCP capsules (two large TCP (L-TCP), one PLA-impregnated large TCP (IL-TCP) and one thin TCP capsule (TN-TCP)). Rats in group II (n = 16) were implanted s.c. with four ALCAP ceramics (two large ALCAP (L-ALCAP), one PLA-impregnated large ALCAP (IL-ALCAP) and one thin ALCAP capsule (TN-ALCAP)). Rats in groups III (n = 16), IV (n = 4) and V (n = 16) were left without implants. Rats in group III (n = 16) were given 4% (w/v) DEMO (pH 7) in drinking water at the day of inoculation and continued up to 7 days postinoculation. Rats in group IV (n = 4) served as a nontreated group. Rats in group V (n = 16) served as normal controls. The results showed that all rats implanted with TCP or ALCAP implants had no intoxication symptoms or side effects such as diarrhea during the treatment period. In contrast, rats given DEMO in drinking water exhibited foul-smelling diarrhea during the treatment period. Microscopic evaluation of blood smears collected from rats receiving DEMO chemotherapy showed an occasional or limited number of stumpy shape (SS) trypanosomes. This study suggests that (1) ceramic drug delivery systems are capable of delivering DFMO in a sustained manner for two months, and were able to cure repeated infections of trypanosomiasis; (2) the use of ceramic implants avoided widely fluctuating, irregular levels of DEMO in the body by keeping sustained levels above minimal effective concentrations; (3) ceramic drug delivery systems provide a pharmacological potentiality for drugs such as DEMO which have been withheld from the market because of severe side effects when administered using conventional methods of drug administration; and (4) DEMO-filled ceramic devices can be implanted subcutaneously in animals that face a threat of lethal protozoal infections in highly infested areas of the world.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31897/3/0000850.pd