ALZET osmotic pumps are miniature, implantable pumps used for research in mice, rats, and other laboratory animals. These infusion pumps continuously deliver drugs, hormones, and other test agents at controlled rates from one day to four weeks without the need for external connections or frequent handling. Their unattended operation eliminates the need for repeated nighttime or weekend dosing. ALZET pumps can be used for systemic administration when implanted subcutaneously or intraperitoneally. They can be attached to a catheter for intravenous, intracerebral, or intra-arterial infusion. ALZET pumps can also be used for targeted delivery, where the effects of a drug or test agent are localized in a particular tissue or organ, by means of a catheter. The pumps have been used to target delivery to a wide variety of sites including the spinal cord, spleen, liver, organ or tissue transplants, and wound healing sites. ALZET pumps have been used in thousands of studies on the effects of controlled delivery of a wide range of experimental agents, including peptides, growth factors, cytokines, chemotherapeutic drugs, addictive drugs, hormones, steroids, and antibodies. Due to the unique mechanism by which ALZET pumps operate, compounds of any molecular conformation can be delivered predictably at controlled rates, independent of their physical and chemical properties. A bibliography of pump work which has been documented in the scientific literature is available, as is information on the osmotic delivery mechanism of ALZET pumps.
ALZET Osmotic Pumps help researchers save critical time by providing continuous delivery of test agents, thereby eliminating the need for frequent, round-the-clock injections. With sizes small enough even for use in mice or young rats, these implantable pumps have proven invaluable in predictably sustaining compounds at therapeutic levels, avoiding potentially toxic or misleading side effects.
ALZET osmotic pumps are an enabling tool for many researchers. A great deal of cutting edge research has been done by scientists who have avoided the limitations inherent with other in vivo delivery methods. Continuous infusion allows effective delivery of agents with short half-lives, and can produce more effective and predictable plasma levels than repeated injections. The ability to deliver drugs locally can isolate compound-specific effects and minimize problems with systemic toxicity.
Neuroscientists have used ALZET pumps to deliver compounds to the brain, the spinal cord, and nerves. The ability to infuse the brain directly circumvents the blood-brain barrier. Growth factor administration has allowed scientists to delve into potential treatments for neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases.
Alzheimer’s AD Animal Models:
Biotechnology researchers have used the pumps to deliver cytokines, growth factors, hormones, and newly-synthesized proteins. Continuous infusion can be advantageous when delivering such agents, as the short half-lives of proteins and peptides can render injections ineffective.
Pharmacologists have used the pumps to target delivery to specific organs and tissues. This decreases the amount of valuable compound which needs to be delivered, isolates compound effects, and avoids potential problems with systemic toxicity. Compounds that cannot be delivered orally can still be tested, and can drive development of more successful chemical structures. Many receptor characterization studies have been done using this method.
Cardiovascular researchers have used the pumps to deliver agents such as renin-angiotensin hormones, nitric oxide synthase inhibitors, and angiogenic factors. Endocrinologists and physiologists have used the pumps to deliver hormones, cytokines, and growth factors. Toxicologists and cancer researchers have used the pump to measure cell proliferation, to understand the process of carcinogenesis more fully, and to investigate the effects of teratogenic compounds when given prenatally. Researchers interested in immunology have infused immunosuppressants, cytokines, and antibodies.
In Vivo Pharmacology
"The majority of chemicals are eliminated considerably faster in small laboratory animals as compared with humans, and constant-rate infusion offers several advantages over conventional, bolus delivery regimens in compensating for this difference." 1
When testing a novel compound in vivo, rapid elimination can result in mistaken assessment of activity. Rats and mice generally eliminate test compounds more rapidly than humans. After a single injection, plasma concentration rises to a peak and then declines rapidly until the compound is eliminated from plasma and tissues. Often the duration of serum activity following a single injection is limited to several hours, hence biological effects either fail to develop or develop poorly:
If no effect is observed following injection, it is difficult to determine whether the compound is inactive or if it simply was not present in adequate concentration and for a sufficient duration to elicit an effect.
Depending on the rate of elimination and the frequency of dosing, injections can result in periods during which drug is absent from plasma and tissues. Such extreme variability in compound exposure over time can influence the expression of drug action.
Thus, the data from such experiments can be misleading as to the nature of compound effects and the dose required to elicit them. Additionally, repeated injections are stressful to the animal and difficult to maintain around the clock.
ALZET pumps are drug discovery tools that offer researchers enhanced control over test compound levels in plasma and tissues. Through continuous infusion, these pumps maintain a well-defined, consistent pattern of drug exposure throughout the duration of the experiment. ALZET pumps ensure that test compounds are present in plasma and tissues for a sufficient duration to allow their biological effects to develop fully and reproducibly. The scientific literature contains many examples where ALZET pumps have facilitated full development of drug effects, including those of proteins, peptides, and other rapidly-eliminated compounds. For more information on in vivo pharmacology, consult our bibliography.
