Modelling and Control of Corticotropin Permeation from Hydrogels across a Natural Membrane in the Presence of Albumin

(1) Background: Skin is a difficult barrier to overcome, especially for molecules with masses greater than 500 Da. It has been suggested that albumin may contribute to more effective penetration of many therapeutic substances. In this study, an attempt was made to use albumin in semi-solid formulations to increase the skin penetration of another peptide—corticotropin (ACTH). (2) Methods: Hydrogels were prepared at two concentrations: 15 mg/g and 20 mg/g corticotropin, then albumin was added to them in different stoichiometric ratios. The degree of ACTH release from hydrogels, both with and without albumin addition, was investigated. For selected hydrogels the process of corticotropin permeation through a model membrane, i.e., pig skin, was examined. (3) Results: The study of corticotropin release showed that the addition of albumin, depending on its amount, may delay or increase the release process. Similarly, a study of ACTH permeation through porcine skin showed that albumin can delay or increase and accelerate ACTH permeation. (4) Conclusions: Hydrogel, applicated on the skin surface, may prove to be a beneficial and convenient solution for patients. It is an innovative way of application ACTH that bypasses the gastrointestinal tract and may result in increased availability of the peptide and its efficacy.

Influence of Concentration on Release and Permeation Process of Model Peptide Substance-Corticotropin-From Semisolid Formulations

The transdermal route of administration of drug substances allows clinicians to obtain a therapeutic effect bypassing the gastrointestinal tract, where the active substance could be inactivated. The hormonal substance used in the study-corticotropin (ACTH)-shows systemic effects. Therefore, the study of the effect of the type of ointment base and drug concentration on the release rate and also permeation rate in in vivo simulated conditions may be a valuable source of information for clinical trials to effectively optimize corticotropin treatment. This goal was achieved by preparation ointment formulation selecting the appropriate ointment base and determining the effect of ACTH concentration on the release and permeation studies of the ACTH. Semi-solid preparations containing ACTH were prepared using Unguator CITO e/s. The release study of ACTH was tested using a modified USP apparatus 2 with Enhancer cells. The permeation study was conducted with vertical Franz cells. Rheograms of hydrogels were made with the use of a universal rotational rheometer. The dependence of the amount of released and permeated hormone on the ointment concentration was found. Based on the test of ACTH release from semi-solid formulations and evaluation of rheological parameters, it was found that glycerol ointment is the most favourable base for ACTH. The ACTH release and permeation process depends on both viscosity and ACTH concentration. The higher the hormone concentration, the higher the amount of released ACTH but it reduces the amount of ACTH penetrating through porcine skin.

Fear and Foxes: An Educational Primer for Use with “Anterior Pituitary Transcriptome Suggests Differences in ACTH Release in Tame and Aggressive Foxes”

The way genes contribute to behavior is complicated. Although there are some single genes with large contributions, most behavioral differences are due to small effects from many interacting genes. This makes it hard to identify the genes that cause behavioral differences. Mutagenesis screens in model organisms, selective breeding experiments in animals, comparisons between related populations with different behaviors, and genome-wide association studies in humans are promising and complementary approaches to understanding the heritable aspects of complex behaviors. To connect genes to behaviors requires measuring behavioral differences, locating correlated genetic changes, determining when, where, and how these candidate genes act, and designing causative confirmatory experiments. This area of research has implications from basic discovery science to human mental health.