Topical drug delivery

In ancient times, human skin was used as a layer for self-expression by painting cosmetic products on it. They used those products as a protection for their skin from the sun and dry environment. Later on in 2000 BCE, the Chinese used topical remedies that wrap in bandages to treat skin diseases. The contact between these topical remedies and skin deliver its therapeutic effect on the skin. The newer development of topical drugs occurred between 130 and 200 AD. This development was made by Claudius Galenus, a Greek physician. He first loaded the herb medication to Western medicine and formulated it as cream. More recently in the 1920s, some observations were made when applying topical skin, such as to determine its systemic effects. In 1938, Zondek successfully managed urogenital infections after applying chloroxylenol on the skin by the use of disinfectant in ointment form. After some years, observations were made from various experiments. These experiments led to the development of skin toxicology in the mid-1970s, including symptoms like irritation, skin inflammation, and skin photo-toxicity upon application of topical drugs. After the development of toxicology, a mathematical model was also created for skin diffusion coefficient formulated by Michaels. This formulation suggests how they related to the aqueous solubility and partition coefficient in skin. == Skin absorption ==

Skin layers The human body's largest organ is the skin layers, which protects against foreign particles. Human skin contains several layers, including the subcutaneous layer, the dermis, the epidermis, the stratum corneum, and the appendages. Each of these layers have an effect on the absorption of topical drug. With this barrier, stratum corneum affects the permeability of topical drugs. Another part of the skin is called the appendages, and it is known as the "shortcut" for topical drug delivery. The shortcut pathway allows the drug molecules to first pass the stratum corneum barrier via hair follicles. When the topical drug molecules transport via the paracellular route, it needs to travel across the stratum corneum, which is a highly fat region, but between the cells. During the transportation of the topical drug molecules, it can bind to the keratin that exists as one of the skin components in the stratum corneum. One common example is thearylamine-type hair dye, after it is applied topically, it will undergo metabolism in the skin through enzyme N-acetyltransferase, thus resulting in a N-acetylated metabolite. The longer the topical drug remains in the skin, the greater amount of it will be metabolized by the underlying enzymes. To reduce such an effect, the topical drug needs to remain on the skin for a shorter period of time. Also, certain amount of topical molecules needs to be applied to the skin and cause metabolic enzymes saturation. The second factor is the lipophilicity of the drug molecules, since the three pathways for absorption are quite lipophilic. The higher lipophilicity of it, the easier of the drug molecules to be absorbed when compared to the hydrophilic drug molecules. The third parameter is the pH level of the skin. The pH of the skin layers are basic, hence basic topical drugs will be absorbed better than acidic topical drugs. These factors are vital to determine the permeability of topical drug delivery. == Skin permeability enhancers ==

Colloidal System Colloidal system is one of the techniques used for topical drug delivery into the skin and functions as skin permeability enhancers. They are known as carriers and can be classified into nanoparticles, liposomes, and nanoemugel. For example, a drug like amphotericin B, is used to treat fungal infections. The drug is loaded into liposome and this carrier enhances the penetration of amphotericin B into the skin, regardless of its molecular weight. Nanoemulgel Nanoemulgel is another type of enhancer for delivery of topical drugs into the skin. The formulation process for nanoemulgel is produced by incorporating the nanoemulsion into a gel matrix. The gels are made out of aqueous bases and it allows for a more rapid release of drugs through dissolution. The use of nanoemulgel enhances patient compliance because the use of gel is less greasy than traditional cream or ointment, hence there is less incident in skin irritation. Nanoemulgel increases the topical drug bioavailability by inserting the lipophilic drug molecules into the oil droplet of the nanoemulgel and it will travel through the skin layers. With its high dissolution rate, the nanoemulgel produces a high concentration gradient toward the skin, thus allowing for a rapid uptake of oil droplet into the stratum corneum. Also, the surfactant being incorporated into the nanoemulgel has the ability to penetrate through the bilayer lipid by interrupting the hydrogen bond between the lipid in the skin to further enhance its permeability. Physical Agents Micro-needles Micro-needle belongs to the physical enhancer to improve absorption of topical drug molecules into the skin. It is known as 'poke and patch' because it uses tiny needles and stick into the skin across the stratum corneum. There are several types of micro-needle, the first one is solid micro-needles. The solid micro-needles are used to project into the skin. Once the needles are removed after insertion, the topical drugs are applied to skin. This enhances the ability of drugs to diffuse across the viable epidermis. The second type is the dissolvable micro-needle. These types of needles are composed of materials that allow them to dissolve after poking into the skin, hence no need to remove the needles after injection. The third type of micro-needle is the swell-able micro-needles, which consist of hydrogel. After poking its needle into the skin, it allows the skin interstitial fluid diffuse into the micro-needles, thus it will swell to diffuse the drug molecules across the skin. It is found that micro-needles are safe and effective in enhancing skin permeability. == References ==