Impact of Pharmacotherapy on Drug Delivery Systems

IntroductionPharmacotherapy can be defined as the treatment and prevention of illness and disease by means of drugs of chemical or biological origin. It ranks among the most important methods of medical treatment, together with surgery, physical treatment, radiation and psychotherapy. Although it is almost impossible to estimate the exact extent of the impact of pharmacotherapy on human health, there can be no doubt that pharmacotherapy, together with improved sanitation, better diet and better housing, has improved people’s health, life expectancy and quality of life.Unprecedented developments in genomics and molecular biology today offer a plethora of new drug targets. The use of modern chemical synthetic methods (such as combinatorial chemistry) enables the synthesis of a large number of new drug candidates in shorter times than ever before. At the same time, a better understanding of the immune system and rapid progress in molecular biology, cell biology and microbiology allow the development of modern vaccines against old and new challenges.However, for all these exciting new drug and vaccine candidates, it is necessary to develop suitable dosage forms or drug delivery systems to allow the effective, safe and reliable application of these bioactive compounds to the patient. It is important to realize that the active ingredient is just one part of the medicine administered to the patient and it is the formulation of the drug into a dosage form or drug delivery system that translates drug discovery and pharmacological research into clinical practice.Indeed the drug delivery system employed plays a vital role in controlling the pharmacological effect of the drug as it can influence the pharmacokinetic profile of the drug, the rate of drug release, the site and duration of drug action and subsequently the side-effect profile. An optimal drug delivery system ensures that the active drug is available at the site of action for the correct time and duration.Drug delivery systemsDrug delivery refers to approaches, formulations, technologies, and systems for transporting a pharmaceutical compound in the body as needed to safely achieve its desired therapeutic effect.· Drug delivery systems according to the physical stateBased on physical state, drug delivery systems may be:- Gaseous (e.g. anaesthetics),- Liquid (e.g. solutions, emulsions, suspensions),- Semisolid (e.g. creams, ointments, gels and pastes) and- Solid dosage forms (e.g. powders, granules, tablets and capsules).· Drug delivery systems according to route of administrationAnother way of differentiating dosage forms is according to their site or route of administration.- Parenteral drug delivery: Drugs can be administered directly into the body, through injection or infusion. Depending on the site of administration into the body it can be differentiated into:a) Subcutaneous injectionb) Intramuscular injectionc) Intravenous injectiond) Intradermal injectione) Intraperitoneal injection- Oral drug delivery: The oral route is the most popular route to administer drugs. Suspensions, tablets, capsules,etc are administered through this route.- Topical drug delivery: Drugs can also be administered on to the skin to enter into the body. Mostly semisolid dosage forms are used for this, including creams, ointments, gels and pastes. However, liquid dosage forms, such as emulsions, or solid dosage forms, such as transdermal controlled drug delivery systems (patches), can also be used.- Transmucosal: In this drugs are administered hrough nasal, buccal/sublingual, vaginal, ocular and rectal routes.· Drug delivery systems according to mechanism of drug releaseAnother system that can be used to differentiate drug delivery systems is according to the way the drug is released. It can be differentiated as:- Immediate release – drug is released immediately after administration.- Modified release – drug release only occurs sometime after the administration or for a prolonged period of time or to a specific target in the body. Modified-release systems can be further classified as:a) Delayed release: drug is released only at some point after the initial administration.b) Extended release: prolongs the release to reduce dosing frequency- Sustained release: These systems maintain the rate of drug release over a sustained period of time.- Controlled release: Controlled-release systems also offer a sustained-release profile but, in contrast to sustained-release forms, controlled-release systems are designed to lead to predictably constant plasma concentrations, independently of the biological environment of the application site. This means that they are actually controlling the drug concentration in the body, not just the release of the drug from the dosage form, as is the case in a sustained-release system.- Targeted drug delivery (smart drug delivery): It is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. The goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue.Disease and Design of drug delivery systemA disease is an abnormal condition that affects the body of an organism. It is often construed as a medical condition associated with specific symptoms and signs. It may be caused by factors originally from an external source, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune diseases, it sometimes includes injuries, disabilities, disorders, syndromes, infections, isolated symptoms, deviant behaviors, and a typical variations of structure and function.Medical therapies are efforts to cure or improve a disease or other health problem. A number of drug molecules have already been developed but development of further more new drug molecule is expensive and time consuming. So, improving efficacy ratio of “old” drugs is considered a good idea. This has been attempted by developing new drug delivery systems that helps in individualizing drug therapy, dose titration, and therapeutic drug monitoring easily. Delivering drug at controlled rate, slow delivery, targeted delivery are very attractive methods and have been pursued vigorously. Drug delivery systems modify drug release profile, absorption, distribution and elimination for the benefit of improving product efficacy and safety. It also ensures patient convenience and compliance.There are some drug molecules which show site specific drug release eg, peptides and proteins. Such drugs cannot show their action without appropriate drug delivery system. So,the increasing number of peptide and protein drugs being investigated demands the development of dosage forms which exhibit site-specific release. Delivery of drugs into systemic circulation through colonic absorption represents a novel mode of introducing peptide and protein drug molecules and drugs that are poorly absorbed from the upper gastrointestinal (GI) tract. Oral colon-specific drug delivery systems offer obvious advantages over parenteral administration. Colon targeting is naturally of value for the topical treatment of diseases of the colon such as Crohn’s disease, ulcerative colitis and colorectal cancer. Sustained colonic release of drugs can be useful in the treatment of nocturnal asthma, angina and arthritis. Peptides, proteins, oligonucleotides and vaccines are the potential candidates of interest for colon-specific drug delivery. Sulfasalazine, ipsalazide and olsalazine have been developed as colon-specific delivery systems for the treatment of inflammatory bowel disease (IBD).Worldwide, over 40 million people are infected with the Human Immunodeficiency Virus (HIV). The High Activity Antiretroviral Therapy (HAART) combines at least three antiretroviral (ARV) drugs and, for over a decade, has been used to extend the lifespan of the HIV-infected patients. Chronic intake of HAART is mandatory to control HIV infection. The frequent administration of several drugs in relatively high doses is a main cause of patient incompliance and a hurdle toward the fulfillment of the pharmacotherapy. High adherence to HAART does not lead to complete HIV virus elimination from the host. Intracellular and anatomical viral reservoirs are responsible for the perpetuation of the infection. Active transport mechanisms involving proteins of the ATP-binding cassette superfamily prevent the penetration of ARV drugs into the brain and may account for the limited bioavailability after oral administration. A new research that addresses from simple organoleptic or technological problems to more complex issues involving the targeting of specific tissues and organs has emerged. With the aim to reduce dosing frequency, to improve the compliance of the existing pharmacotherapy and to target viral reservoirs, the design of drug delivery systems is becoming complementary to new drug discovery.ConclusionWhenever a person suffers from a disease, he/she requires a medical treatment and every one of us prefer the safe, effective, economic and a convenient one. This can only be achieved by development of appropriate drug delivery system. No matter how dosage forms are classified, the role of the drug delivery systems is to allow the effective, safe, and reliable application of the drug to the patient.For the proper Pharmacotherapy, delivery systems should allow and facilitate the drug to reach its target site in the body. For example, a tablet formulation containing an antihypertensive drug must disintegrate in the gastrointestinal tract, the drug needs to dissolve and the dissolved drug needs to permeate across the mucosal membrane of the gastrointestinal tract into the body. So, for the development of dosage forms the formulation scientist needs to optimize the bioavailability of the drug.Similarly, the delivery system is to allow the safe application of the drug. This includes that the drug in the formulation must be chemically, physically and microbiologically stable. Side-effects of the drug and drug interactions should be avoided or minimized by the use of suitable drug delivery systems. The delivery systems also need to improve the patient’s compliance with the pharmacotherapy by the development of convenient applications. For example, one can improve patient compliance by developing an oral dosage form where previously only parenteral application was possible.Finally, the delivery system needs to be reliable and its formulation needs to be technically feasible. However, for any application of a drug delivery system on the market, the dosage form needs to be produced in large quantities and at low costs to make affordable medicines available. Therefore, it is also necessary to investigate the feasibility of the developed systems to be scaled up from the laboratory to the production scale.

Combat Psoriasis! – Strengthen Your Immune System

Most people believe that psoriasis is a skin condition. However, psoriasis is in fact an inflammatory disease of the immune system. In patients with psoriasis, certain immune cells are activated. These cells overproduce inflammatory proteins, such as tumor necrosis factor (TNF), which cause skin cells to grow too quickly. The skin cells build up causing raised red patches, often with silvery scales known as plaques.Inflammation is thought of as the body’s normal response to injury or infection. However, if the response is too severe or prolonged, then this may become a problem in itself. Inflammation responses are generally regulated by mechanisms in our immune system. If the immune system is working correctly to maintain internal equilibrium, the inflammatory responses will adjust to their normal physiological state. If the immune system misfires, it causes the excess inflammation and accelerated growth of cells.T-cells (white blood cells) are a type of immune system cell which are very important to the internal process of psoriasis. T-cells naturally patrol throughout the body looking for foreign substances called antigens. These antigens usually come from the outside in to our bodies as bacterium or virus. The invasion of these antigens activates the T-cells, which then initiates an immune response to neutralize the antigen.In psoriasis, it is not clear what happens, but the activated T-cells end up in the skin. This may be directly related to the genetic predisposition in people who develop psoriasis. The T-cell will recognize and target the antigen on the surface. The specific antigens responsible for psoriasis are not know, but some infections like strep throat are believed to trigger some cases of guttate psoriasis.If the T-cells are not activated, the immune response and cycle of psoriasis never begins. But if the T-cell does become activated, the immune system response is initiated which includes the release of cytokines. Cytokines are proteins that the immune system uses to communicate messages. The message that cytokines tell the skin is to reproduce and grow at an accelerated rate. Cytokines also set off other reactions including inflammation, and activation of additional T-cells. The end result is a pile up of dead skin cells that have grown too fast and have moved to the surface of the skin as white scale.So what lies ahead in research knowing that psoriasis is driven by the immune system? Of course there are already the many drugs of choice which suppress the body’s immune system. The problem with many of these harsh drugs is that they can cause other health problems and unpleasant symptoms.Your immune system does a remarkable job of defending you against disease-causing microorganisms. But sometimes it fails. Is it possible to intervene in this process and make your immune system stronger? The idea of boosting your immune system is intriguing. But one must realize that the immune system is precisely that – a system. To function properly it requires a balance and harmony. There is still much research to be done on the complexities and interconnections of the immune response.But what if it was possible to intervene in this process and make your immune system stronger? What if you improve your diet? Take certain vitamins or herbal preparations? Make other lifestyle changes toward reaching that goal of balance and harmony in the hope of producing a near-perfect immune response?Many researchers are exploring the effects of diet, exercise, age, psychological stress, herbal supplements, and other factors on the immune response, both in animals and in humans. Some very interesting preliminary results are emerging as researchers still try to understand how the immune system works and how to interpret measurements of the immune function.But meanwhile, why not adopt some healthy-living strategies and choose a healthy lifestyle.As we have discussed in some of our other articles, following general good health habits are the single best steps you can take toward keeping your immune system strong and healthy. Every part of your body, including your immune system, functions better when protected from environmental assaults and bolstered by healthy-living strategies such as these:• If you smoke, quit!• Improve your diet. Eat a diet high in fruits, vegetables, and whole grains, and low in saturated fat.• Exercise regularly to maintain a healthy weight and control your blood pressure• Manage your stress.• Drink alcohol only in moderation.• Get 7-8 hours of adequate sleep per day.• Take steps to avoid infection such preventing cuts and wounds and washing your hands frequently. • Make regular appointments to have medical screening tests for people in your age group and risk category.In order for your immune system warriors to win the fight, you need good, regular nourishment. If you are one of the many people who do not like vegetables, and you think your diet is not providing all of the nutrients you need then you should consider taking a multiple daily vitamin.Recommended Vitamins and minerals that have been studied to have a positive effect on the immune system are:• Vitamin A• Vitamin B2• Vitamin B6• Vitamin C• Vitamin D• Vitamin E• Zinc• SeleniumBesides our regular intake of healthy foods and vitamins, we should not discount the benefits of herbal preparations. Even though further studies are needed to confirm or disprove the beneficial results that herbal supplements have on the immune system, who is to say that what Grandma took for years and to protects her from illness doesn’t work?Some of the supplements that researchers believe are worth more attention are:Probiotics. These are good bacteria that can safely reside in your digestive system. There are some researchers, including some at Harvard Medical School, that are finding evidence of a relationship between this “good” bacteria and the immune system. For instance, it is now known that certain bacteria in the gut influence the development of aspects of the immune system, such as correcting deficiencies and increasing the numbers of certain T cells.When you go shopping, you will find probiotics listed on the labels of dairy products, drinks, cereals, energy bars, and other foods. However, one must be careful not to think that by taking excessive amounts of good bacteria that it will help the immune system even more. Researchers are still trying to find the direct connection between taking these products and improving immune function. It has not been shown whether taking probiotics will replenish the good bacteria that get knocked out along with “bad” bacteria when you take antibiotics.Echinacea. This is one of the most well-known herbal supplements used as an “immune stimulant,” and advertised to be able to prevent or limit the severity of colds. However, it is recommended by most experts not to take echinacea on a long-term basis to prevent colds.Just be aware that Echinacea can also cause potential side effects for persons with ragweed allergies including cases of anaphylactic shock. Injected echinacea in particular has caused severe reactions.Garlic. Researchers have seen garlic work against bacteria, viruses, and fungi in laboratory tests. A 2006 research studied the rates for certain cancers and garlic and onion consumption in southern European populations and found an association between the frequency of use of garlic and onions and a lower risk of some common cancers. However, until more is known, it is too early to recommend garlic as a way of treating or preventing infections or controlling cancer.Ginseng. This herbal supplement is known for its ability to stimulate the immune function. It is still unclear how the root of the ginseng plant works. The National Center for Complementary and Alternative Medicine (NCCAM) considers there have not been sufficient high quality large studies performed to support the claims. They are currently involved in supporting research to understand Asian ginseng more fully.Finally, we will discuss the most important relationship between stress and the immune system. We know stress has a negative effect on our minds and bodies and is a main trigger for psoriasis and other diseases. However, stress is different for everyone and is difficult to define. What may be a stressful situation for one person is not for another.Therefore, most scientists studying the relationship of stress and immune function do not study a sudden, short-lived stressor. They study frequent and more constant stressors known as chronic stress. These stressors can be caused by relationships with family, friends, co-workers or sustained challenges at work.Many researchers have reported that stressful situations can reduce various aspects of the cellular immune response. Reports suggest that psychological stress affects the immune system by disrupting communication between the nervous system, the endocrine (hormonal) system, and the immune system. These three systems must work in close coordination and “talk” to one another using natural chemical messages.Some research teams speculate that long-term chronic stress releases a long-term trickle of stress hormones called glucocorticoids. These hormones affect the thymus, where lymphocytes are produced, and inhibit the production of cytokines and interleukins, which stimulate and coordinate white blood cell activity.Managing your stress is extremely vital for the proper function of your immune system in order for it to combat your psoriasis and other diseases. So be sure to take time to learn and educate yourself on stress management techniques and you may want to join some forums to learn from others.Following sections summarize some of the most active areas of research into these topics. In the meantime, general healthy-living strategies are a good way to start giving your immune system the upper hand