Discovery of Transdermal Penetration Enhancers by High-throughput Screening
In the field of drug delivery, the core aspect is to deliver active pharmaceutical ingredients (API) to the targeted location with a specified
amount at the right time without causing any side effects. The drug concentration in the body after a certain elapsed time must achieve to the
therapeutic concentration, which is designed to bind most effectively to the targeted cell receptors. The range of drug concentrations within the
therapeutic effect is called target therapeutic window. If the drug concentration is above this window it will cause overdose and side effect;
meanwhile, if it is below this window it will generate no effect for taking the drug.
Fig1. Drug Concentration Window after an Elapsed Time
Drug delivery has evolved through many forms, which are designed to follow the basic principle of delivering drugs to the body. Two
traditional forms are oral and intravenous (IV) delivery routes. These two are commonly used due to their efficacy and reproducibility. However,
tablets forms are susceptible to pass the liver metabolism, which might interfere with the drug efficacy and toxic to the body. For IV route, it
provides a fast time response, but less patient compliance.
Fig2. Drug Delivery Method Timeline
Transdermal delivery method, as compared with oral and IV routes, provides safety to patients since it does not go through the liver
metabolism and it gives patient's compliance due to its comfort delivery method. One of the requirements for transdermal delivery method is the
effectiveness of the active ingredient to pass through the skin layer (stratum corneum). This layer is responsible for the barrier between the
transdermal drug and the body. Thus, transdermal drug delivery method must be accompanied by the use chemical penetration enhancers (CPEs),
which aids the permeability of the drug through the stratum corneum. In the industry of drug discovery and transdermal drug delivery,
finding the CPEs to increase the enhancement ratio (ER) has been exploring with the use of high-throughput screening method.
Fig3. Different methods to enhance chemical penetration: Iontophoresis (b), Electroporation (c), Sonophoresis (a,c), Microneedles (d), Chemical penetration enhancers (CPE) (a,c)