Desenvolvimento de Medicamentos Inovadores para Acne – Abrindo Novos Caminhos

The general aim of the present project is to set the basis for the development of novel topical medicines against acne vulgaris. One first specific aim is to achieve an optimized formulation based on the described innovative SNEDDS or NE of Capryol® 90 as lead formulation, which could be considered suitable for cutaneous administration in the treatment of acne and potentially safe for use by pre-adolescents and pregnant women, according to the following criteria: rational selection of its components, considering literature information on their effect on human skin; physicochemical and organoleptic attributes; efficacy in at least one of the in vitro models of acne vulgaris hallmarks (keratinocyte proliferation, C. acnes overgrowth and/or dysbiotic shift, anti-inflammatory effect, sebocyte proliferation and/or sebum production) and concomitant efficacy against strains associated with Malassezia folliculitis; safety (in in vitro reconstituted skin models) and acceptability... suitable packaging and stability. With exception of stability studies, this is expected to be achieved during the first 6 months. A second specific aim is to test whether any of the previously developed 5a-Reductase inhibitors have potential as a candidate anti-acne drug. To provide evidence of such, we intend to characterize the compounds’ effect on androgen receptor (AR), their selectivity against 5a-Reductase subtypes and ability to inhibit sebum production. Simultaneously, we intend to study their pre-formulation properties, to select the best suitable candidate for the development of a new drug product. This is expected to be achieved during the first 9 months of the project, and overlaps in time the previous objective. A third specific aim is to develop follow-up combination formulations by incorporating a retinoid (trifarotene) and the most promising 5a-Reductase inhibitor to obtain a medicine potentially effective in all acne hallmarks. These new formulations will be tested to meet the criteria already defined for the previous formulations. This aim will be pursued approximately during the second half of the project timeline.