Gene/Protein Disease Symptom Drug Enzyme Compound
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Synthetic polypeptides consisting of copolymers of glutamic acid and leucine have been shown to be useful materials for the fabrication of practical, biodegradable delivery vehicles for narcotic antagonists. Model delivery vehicles in film form were prepared from copolymers containing 10 mole percent to 40 mole percent glutamic acid, and loaded with 10% to 40% naltrexone by weight. The naltrexone was found to be released by diffusion, exhibiting diffusion coefficients that varied as a function of the glutamic acid content and the initial naltrexone loading. A wide range in diffusion coefficients were achieved (0.31 x 10-7 cm2/hr to 120 x 10-7 cm2/hr), leading to release rates within practical ranges of interest for meeting the program goals. We have demonstrated that the polypeptides can be fabricated into dosage forms that are amenable to administration by trochar. For example, rods 0.4 mm to 0.8 mm in diameter containing as much as 40% naltrexone by weight were extruded using a simple compression mold and die arrangement. An in vitro evaluation of the rods showed that antagonist is released by diffusion at a continuously decreasing rate, a behavior similar to that observed with the film devices that were, nonetheless, capable of blocking an AD80 challenge of morphene sulfate in mice for more than 30 days. One of the most promising delivery vehicles that we have developed to date consists of a polypeptide tube filled with a naltrexone/polypeptide core. Preliminary experiments have shown that these devices may be capable of administering high, constant rates of release for prolonged periods of time. Additional work, however, is required to develop techniques for the preparation of reproducible delivery vehicles.
Natl Inst Drug Abuse Res Monogr Ser 1976 Jan
PMID:Use of synthetic polypeptides in the preparation of biodegradable delivery vehicles for narcotic antagonists. 96 33

Synthetic polypeptides consisting of copolymers of glutamic acid and leucine have been shown to be useful materials for the fabrication of practical, biodegradable delivery vehicles for narcotic antagonists. Model delivery vehicles in film form were prepared from copolymers containing 10 mole percent to 40 mole percent glutamic acid, and loaded with 10% to 40% naltrexone by weight. The naltrexone was found to be released by diffusion, exhibiting diffusion coefficients that varied as a function of the glutamic acid content and the initial naltrexone loading. A wide range in diffusion coefficients were achieved (0.31 x 10(-7) cm2/hr to 120 x 10(-7) cm2/hr), leading to release rates within practical ranges of interest for meeting the program goals. We have demonstrated that the polypeptides can be fabricated into dosage forms that are amenable to administration by trochar. For example, rods 0.4 mm to 0.8 mm in diameter containing as much as 40% naltrexone by weight were extruded using a simple compression mold and die arrangement. An in vitro evaluation of the rods showed that antagonist is released by diffusion at a continuously decreasing rate, a behavior similar to that observed with the film devices that were, nonetheless, capable of blocking an AD80 challenge of morphine sulfate in mice for more than 30 days. One of the most promising delivery vehicles that we have developed to date consists of a polypeptide tube filled with a naltrexone/polypeptide core. Preliminary experiments have shown that these devices may be capable of administering high, constant rates of release for prolonged periods of time. Additional work, however, is required to develop techniques for the preparation of reproducible delivery vehicles.
Natl Inst Drug Abuse Res Monogr Ser 1975
PMID:Use of synthetic polypeptides in the preparation of biodegradable delivery vehicles for narcotic antagonists. 123 83

One approach to treating drug abuse uses antidrug antibodies to immunize subjects against the illicit substance rather than administering therapeutics that target the specific CNS site of action. At present, passive vaccination has recognized efficacy in treating certain gross symptoms of drug misuse, namely, motor activation, self-administration, and overdose. However, the potential for antibodies to prevent drug-induced changes involving finer cognitive processes, such as benzodiazepine-associated amnesia, remains unexplored. To address this concept, a flunitrazepam hapten was synthesized and employed in the generation of a panel of high affinity monoclonal antibodies. Anti-flunitrazepam mAb RCA3A3 ( K d,app = 200 nM) was tested in a mouse model of passive immunization and subsequent mole-equivalent challenge with flunitrazepam. Not only was flunitrazepam-induced sedation prevented but immunization also conferred protection to memory consolidation as assessed through contextual and cued fear conditioning paradigms. These results provide evidence that immunopharmacotherapeutic blockade of drug intoxication also preserves complex cognitive function.
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PMID:Prevention of drug-induced memory impairment by immunopharmacotherapy. 1892 91