A New Hyaluronic Emulgel of Hesperetin for Topical Application-An In Vitro Evaluation.

The present study aimed to formulate and characterize a hesperetin formulation to achieve adequate deposition and retention of hesperetin in the epidermis as a target for some cosmetic/dermatological actions. To derive the final emulgel, various formulations incorporating different proportions of Polysorbate 80 and hyaluronic acid underwent testing through a Box-Behnken experimental design. Nine formulations were created until the targeted emulgel properties were achieved. This systematic approach, following the principles of a design of experiment (DoE) methodology, adheres to a quality-by-design (QbD) paradigm, ensuring a robust and purposeful formulation and highlighting the commitment to a quality-driven design approach. The emulsions were developed using the phase inversion method, optimizing the emulgel with the incorporation of hyaluronic acid. Physically stable optimized emulgels were evaluated for their globule size, surface charge, viscosity, pH, electrical conductivity, and hesperetin content. These assays, along with the temperature swing test, were used to select the optimal formulation. It was characterized by a droplet size, d[4,3], of 4.02 µm, a Z-potential of -27.8 mV, an O/W sign, a pH of 5.2, and a creamy texture and proved to be stable for at least 2 months at room temperature. Additionally, in vitro release kinetics from the selected emulgel exhibited a sustained release profile of hesperetin. Skin assays revealed adequate retention of hesperetin in the human epidermis with minimum permeation. Altogether, these results corroborate the promising future of the proposed emulgel in cosmetic or dermatological use on healthy or diseased skin.

Similarity-Based Virtual Screening to Find Antituberculosis Agents Based on Novel Scaffolds: Design, Syntheses and Pharmacological Assays.

A method to identify molecular scaffolds potentially active against the Mycobacterium tuberculosis complex (MTBC) is developed. A set of structurally heterogeneous agents against MTBC was used to obtain a mathematical model based on topological descriptors. This model was statistically validated through a Leave-n-Out test. It successfully discriminated between active or inactive compounds over 86% in database sets. It was also useful to select new potential antituberculosis compounds in external databases. The selection of new substituted pyrimidines, pyrimidones and triazolo[1,5-a]pyrimidines was particularly interesting because these structures could provide new scaffolds in this field. The seven selected candidates were synthesized and six of them showed activity in vitro.