The Pre-Collegiate Global Health Review
Transdermal Patches: Current and Future Implications of a Non-Invasive Cure for Obesity
Jihyun (Olivia) Lim, Chadwick International, Incheon, South Korea

Summary
Obesity and being overweight are looming illnesses threatening worldwide global health. Traditional methods such as oral or injection administration, have low bioavailability and often result in adverse effects, making them high-risk and invasive due to their surgical nature. However, the emergence of the Transdermal Drug Delivery System, particularly transdermal patches, has provided a promising solution by minimizing risk and alleviating pain associated with treatment. Despite the use of advantageous transdermal patches in several therapeutic areas, the safety of transdermal patches in human applications remains a controversial issue.
Given the prevalence of obesity, various factors significantly affect people worldwide, including structural racism, discrimination, poverty, food insecurity, housing instability, and lack of access to quality healthcare. Obesity results from excessive fat accumulation, such as white adipose tissue fat (WAT), impairing health. Functioning for homeostasis and energy balance, adipose tissues consist of white WAT and brown adipose tissue (BAT). WAT stores excess energy like triglycerides while BAT dissipates stored energy as heat, simply saying that WAT stores energy but BAT releases it. While 1 billion people worldwide are obese nowadays - 650 million adults, 340 million adolescents, and 39 children, many patients who develop obesity or are overweight receive treatment at a late stage due to their negligence (Trust for America’s Health, 2022). The growing incidence of obesity is to be addressed as it leads to further inflammation such as type 2 diabetes, heart disease, sleep apnea, and potential cancers including breast, colon, and more.

Figure 1: The Rising Trend of Adult Obesity in the United States (Statista, 2022).
Currently, oral and injection administration are widely used systemic drug delivery methods for the treatment of obesity. While effective in delivering small molecular drugs and macromolecular drugs of proteins respectively, oral and injection administration are associated with a great risk of low drug availability, pain, decreased blood concentration, and adverse effects. Moreover, due to their broad targeting spectrum, these agents have faced challenges from the undesired side effects on other organs. Transdermal Drug Delivery System (TDDS) is emerging as an alternative procedure to address these limitations, revolutionizing the field as a non-invasive process. As the skin has a large surface area of the accessible site, TDDS is an accessible method that applies a drug formulation onto intact and healthy skin. Specifically, TDDS enables penetration circumventing needle phobia, minimizing the risk of toxic effects, and improving patient compliance for those who vomit or rely on self-administration (BMC, 2021). Among several TDDS for such drugs as estradiol, fentanyl, testosterone, disposable transdermal patches are arising as treatment today.

Figure 2: How Transdermal Patch Works (Biotextiles, 2019).
Transdermal patches are equipped with hundreds of detachable polymeric microneedles (MN) for the delivery of drugs to subcutaneous WAT bloodlessly. Each of these microneedles consists of drug-loaded nanoparticles (NP) and a cross-linked matrix to effectively deliver drugs into subcutaneous adipose tissue. These microneedle-based patches reduce treated fat pad size and increase energy expenditure by transforming calorie-storing white fat into calorie-burning brown fat, also known as browning, to reduce the excessive fats in the human body. Transdermal patches have overcome the challenges of side effects, drug toxicity, and low permeability of traditional methods such as browning (BMC, 2021). The use of MN patches ensures uniform plasma levels, reduces the dosing frequency, and enables easy removal of the patches from the skin individually (Pharmapproach, 2020).
Furthermore, the browning efficacy of the transdermal patches for type-2 diabetes in vivo was corroborated by the diet-induced obesity mouse model. The mice were treated with MN patches every 3 days and microneedles penetrated the mouse skin at the inguinal site as evidenced by the trypan blue staining of the MN-treated tissue. Importantly, the delivery of browning agents locally reduced the inguinal fat pad, especially revealing smaller sizes of adipocytes in WAT on the areas with drug-containing patches. Moreover, brown adipocyte genes were highly induced only in the treated side, indicating the successful restriction of browning effects that minimize undesired side effects of MN patches, unlike other conventional methods. Taken together, MN patches have increased energy expenditure and fatty acid oxidation, controlled effective body weight control, and improved insulin sensitivity.

Figure 3: Chemical Enhancers of Transdermal Patches (Springer, 2020).
However, one challenge transdermal patches have is skin irritation from the limited efficacy of individual chemicals in disrupting the skin barrier at low concentrations (Frontiers, 2022). In fact, the low permeability of the skin restricts the number of drugs to be delivered via this method. A multicomponent mixture of chemicals has been developed by complementing the limitations of MN patches providing high skin permeabilization potency without causing irritation. Widely accepted chemical permeation enhancers for multicomponent mixtures include water, hydrocarbons, amines, amides, esters, alcohol, and more. Unfortunately, these chemical enhancers performed a poor permeation limited across the top layers of the stratum corneum, resulting in poor transdermal delivery of drug molecules (Frontiers, 2022). For instance, the high partition coefficient for lipid fluidizers shows limits in practical use due to the poor solubility in the aqueous form (Frontiers, 2022).
Until recently, TDDS, especially the transdermal patches proved to be a promising solution for obesity and overweight. Nevertheless, the evidence of multicomponent mixtures for skin irritation was favorable only to some extent in practical applications. This means that robust studies for further development are warranted to overcome skin irritation and validate efficiency in humans to minimize the risk of obesity and overweight. As a result, approaches to combat applicable solutions and continue support in research funding have noteworthy value in promoting global health as a result.
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