ARDEB 1001

Development and in vitro/in vivo Evaluation of Innovative Drug Delivery System Aspasomes with Natural Ingredients for the Treatment of Androgenetic Alopecia

Human skin shows selective permeability for the permeation of many drugs. The stratum corneum layer in the epidermis, the top layer of the skin, acts as a restrictive barrier for drug permeation. Following the discovery of liposomes, which are pioneers in increasing skin penetration, drug carrier systems with different lipid structures have been discovered in recent years and have been observed to be effective. Discovered by Gopinath et al. in 2004, aspasomes are defined as a double-layered vesicular system formed by ascorbyl palmitate. Ascorbyl palmitate is the ester form that is more lipophilic, stable and bioavailable than ascorbic acid. Ascorbyl palmitate, which can be stored in the lipid cell membrane until used in the body, has important advantages that make aspasomes stand out in dermal application, with its properties that increase drug solubility and permeability in the skin. Androgenetic alopecia (AGA) is also known as male pattern hair loss (baldness), which generally begins in the 20s and 30s and typically begins with bitemporal regression of the frontal hairline, resulting in thinning of the hair, especially at the crown, and complete hair loss in the center of the crown. In the treatment of AGA, local use of liquid and foam forms of minoxidil at 2% and 5% concentration has been approved by the FDA for the treatment of hair loss in men and women. In addition, finasteride, an antiandrogen and inhibitor of the type 2 5-α-reductase enzyme that converts testosterone to dihydrotestosterone (DHT), is approved for use only in men in the treatment of AGA. However, the fact that these two compounds did not meet the expectations revealed the necessity of new approaches to formulate alternative compounds in treatment and to use them more effectively with drug delivery systems. Caffeine, a naturally occurring phosphodiesterase inhibitor, can support proliferation by increasing cAMP levels in cells and stimulating cell metabolism. In this way, it can prevent the shrinkage of the hair follicle caused by testosterone/DHT. Its direct effect against apoptosis induced in AGA by phosphodiesterase inhibition has been described. Epigallocatechin gallate (EGCG), which is the main active component of Camellia sinensis L. (green tea) in catechin structure, is an important bioactive molecule that can prolong the anagen phase and stimulate human hair growth through its proliferative and antiapoptotic effects on dermal papilla cells. It is a DHT inhibitor that prevents insulin-like growth factor (IGF-) 1 levels from decreasing. IGF-1 promotes the transition from the telogen phase to the anagen phase. Rosmarinic acid (RA), a natural powerful antioxidant, is known to suppress testosterone and DHT activity, increase cell viability in a time-dependent manner, and may be a potential therapeutic agent for promoting hair growth and preventing AGA. Physcion is an anthroquinone derivative compound, has no formulation development studies and 5-α-reductase inhibitory activity, and is thought to have a hair loss preventive effect. In project, detailed characterization studies and optimum formulation components of aspasomes to be developed with natural origin compounds that may be effective for the four different AGA treatments mentioned above will be determined, cell culture studies, stability and permeation studies through the mouse abdominal skin will be carried out. At the end of the permeation study, the phosphodiesterase and 5-α-reductase enzyme inhibition effects and total antioxidant capacity of the active substance combination released from aspasomes, which are targeted to reach the dermis layer and will be viewed with a confocal microscope, will be examined. Within the scope of in vivo studies, formulation effectiveness will be evaluated by determining hair growth promoting activity, determining hair follicle morphology and number, and determining IGF-1 in the hair follicle on the back skin of C57BL/6 mice.

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