The promise of drug delivery strategies is in their potential to improve current treatments and create opportunities for experimental therapy. Drugs that are absorbed through the skin or the nose instead of taken as a pill could help people reduce side effects and improve adherence. Drugs that are injected daily could instead be given through an implant once a year or through skin patches. Time release technology might allow for drugs now taken three or more times a day to be taken once a day or even once a week.
These methods are already being used to treat other conditions. Many companies probably feel that it's cheaper and safer to spend money on developing drugs that don't rely on experimental drug delivery. However, the next leap in treating HIV disease will likely require that researchers and drug makers think beyond the status quo.
HIV is not the only disease where people must take medicines exactly as prescribed for long periods of time. Diabetes and tuberculosis are two other conditions where strict drug schedules often present challenges. Until recently, however, drug makers basically offered only two ways to take most medicines -- as a pill or a shot.
Because most people prefer taking a pill over an injection, research in HIV and most other diseases has focused almost solely on developing drugs that are taken by mouth, usually as a pill. Only when a compound can not make it through the digestive system have companies considered making drugs that need a direct route to the bloodstream. Often, such drugs weren't developed at all as companies feared patients wouldn't use them.
People living with HIV are all too familiar with the shortcomings of current anti-HIV drugs. All of them demand near perfect adherence. Some cause hard-to-manage side effects like nausea, vomiting and diarrhea because of how they affect the digestive system. Also, the size of pills and the number that must be taken are a barrier for many, even those who do not find these strict pill schedules troublesome.
As is true with many drugs in pill form, most anti-HIV drugs require that people take a larger dose of the drug by mouth than is necessary by injection. This is because only a small percent of what starts out in the stomach makes it into the blood.
Recent advances offer exciting alternatives to the handfuls of pills that many people now take. One area of intense focus is the search for needle-free devices. More and more medicines are now delivered to the bloodstream less intrusively, through skin patches, gels and creams, inhaled products, nasal sprays and small patches that attach to the gums in the mouth. In the future, consumers may be given things that look like pens, or a sort of air gun. Both use air pressure to shoot a dose of medicine through the skin without a needle.
Getting Drugs Through the Skin
Creams and gels that are rubbed into the skin have been used for years to deliver pain medication and infection fighting drugs to an affected site of the body. These include, among others, gels and creams for vaginal yeast infections, topical creams for skin infections and creams to soothe arthritis pain.
New technologies now allow other drugs to be absorbed through the skin (transdermal). These can be used to treat not just the affected areas (for example, the skin) but the whole body (systemic). A growing number of medicines are now available as transdermal patches.
Patches usually have an adhesive rim that sticks to the skin, while the center is coated with a film of the active drug. The drug is slowly absorbed through the skin making its way into the bloodstream. Examples include patches that contain testosterone, estrogen, pain relievers and nicotine (to help people quit smoking). Other patches deliver anti-seizure medication like gabapentin (Neurontin).
Controlled release of the medicine is one of the greatest advantages of patches. In some cases, the active drug is mixed with another substance that controls how quickly it's absorbed through the skin. Also, a thin net-like layer of material can be placed between the drug and the skin to control absorption. This allows most patches to be worn continually for at least 24 hours. Some can be worn for several days.
Another form of transdermal drug delivery includes devices that use air pressure to inject a small stream of medicine through the top layers of the skin. Air pressure guns have been used for several years to give vaccines to children. Small, disposable pen-like devices are also available for diabetics who take insulin daily. Researchers working on HIV gene therapy have experimented with this technology to inject genetic material through the skin or into muscle.
Getting Drugs Through Mucous Membranes
Many drugs, when delivered to the lungs or inside the nose, are quickly absorbed into the bloodstream. Inhaled drugs now in development include a broad range, from pain relievers to an array of vaccines. In what could be a major advance in treating diabetes, an inhaled form of insulin is now being tested.
Also, expect to see other new products that are absorbed through mucus membranes (thin layers inside the nose, mouth, vagina and rectum). These include nasal sprays, buccal patches and suppositories. Butorphanol (Stadol), a pain reliever, is now available as a nasal spray. Several recent papers indicate nasal sprays may be an ideal way to deliver some peptide-based drugs that cannot be taken as pills.
Buccal patches are small patches that stick to the inside of the cheek. They slowly release medicine over time through the mucous membranes in the mouth. Buccal patches are now used to deliver antifungal and heart medicines. Buccal forms of anti-asthma and pain relief medicines are also being studied.
An ideal place to deliver drugs is through the rectum with suppositories. The lining of the rectum is porous and can absorb drugs quickly into the bloodstream. Drug makers have been slow to develop suppositories because they fear that most people are unwilling to use a drug that's put into the rectum.
However, nurses have long used them to care for infants and adults who are unable to take pills. Suppositories are used most often with anti-nausea and anti-asthma drugs, as well as hormones. Recently, researchers began to see their potential and are now developing new drugs to be given this way.
Drug Delivery and HIV
There are currently limitations to the technologies described above, particularly with regard to current anti-HIV drugs. Most are made of molecules too large to pass easily through the skin or mucous membranes. For some drugs, the quantities that must be given for each dose are far too large to be made into patches or suppositories. However, these obstacles may not be insurmountable.
Researchers have already found chemicals that help larger molecules pass through the skin. Other chemicals cause drugs to stay in the body longer or to make it into cells more easily. The substantial improvements in treating hepatitis C with pegylated interferon is just one example of success in this area.
While much of this research is new, it demands our attention. It's not difficult to imagine the benefits of using anti-HIV drugs in small doses only once a day or even once a week by a patch or inhaler.
While these treatments do not exist today, the technology to create and test them does. Dozens of companies are developing and improving them. These are genuinely exciting developments. They have the potential to greatly ease the lives of people living with HIV, if not today then certainly in the future -- as long as people living with HIV and their advocates push for them.
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