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Phosvitin shows chelating abilities, an affinity for ACTH (corticotropin), growth factors, antioxidant properties, and acidic nature. An attempt was made to use this protein in hydrogels as a transporter of other protein substances: somatotropin (STH) and (ACTH). The aim of the study was to evaluate the effect of phosvitin on the permeation of ACTH and STH from semi-solid forms of the drug applied to the skin. Four hydrogel substrates were prepared using natural polymers: sodium alginate, methylcellulose, and starch. Based on the evaluation of physicochemical parameters, the hydrogel with the most favorable properties was selected and loaded with the active substances STH and ACTH, followed by the addition of phosvitin. A study of the permeation of STH and ACTH through the artificial cellulose membrane and through porcine skin was carried out without and with the addition of phosvitin. The effect of protein substances on rheological and textural parameters was studied. The evaluation of physicochemical parameters showed a favorable effect of STH and Phosvitin on the stability of the hydrogel with 4% methylcellulose and no effect of ACTH. All prepared formulations showed a reaction close to the natural pH of human skin. In the porcine skin permeation study, the addition of Phosvitin to the hydrogel with STH caused a slight increase in the amount of STH permeated and an increase in the time for STH to permeate porcine skin by 30 min. Phosvitin caused an increase in the amount of ACTH permeated through porcine skin almost twofold. Phosvitin may prove to be a promising permeation promoter for model protein-peptide substances when applied to the skin surface.

This work is part of the current research trend to develop a hydrogel carrier of insulin to promote wound healing. Topically applied insulin promotes keratinocyte proliferation and migration, increases collagen synthesis, reduces inflammation and oxidative stress, and exhibits antimicrobial activity. The aim of this study was to design an insulin hydrogel matrix based on selected cellulose derivatives (methylcellulose, hydroxyethylcellulose, and hydroxypropylmethylcellulose) and chitosan. Rheological parameters of the formulations were evaluated using rotational rheometry and an oscillation test. Textural tests were performed. In vitro pharmaceutical insulin availability studies were carried out using the innovative Strat-M ® membrane to imitate the skin barrier. It was found that the pharmaceutical formulation of insulin based on chitosan and methylcellulose showed an acceptable balance between rheological and textural parameters and ease of application. The API was released from the carrier in a prolonged manner, eliminating the need to apply the formulation several times per day. The developed hydrogel shows potential for use in clinical practice.

Insulin has shown efficacy in the treatment of hard-to-heal wounds, which is mainly due to its role in regulating oxidative stress and inflammatory reactions. The aim of this study was to develop an insulin-hydrogel carrier based on Sepineo™ P 600 and Sepineo™ PHD 100 for application to lesional skin. Preformulation studies of the developed formulations were performed in terms of analysis of the pharmaceutical availability of insulin from the hydrogels through the Strat-M ® membrane, and rheological and texture measurements. Insulin is released in a prolonged manner; after a time of 6.5 h, 4.01 IU/cm 2 (53.36%) and 3.69 IU/cm 2 (47.4%) of the hormone were released from the hydrogel based on Sepineo™ P 600 and Sepineo™ PHD 100, respectively. Rheological analysis showed that the hydrogels tested belong to non-Newtonian, shear-thinning systems with yield stress. The insulin-hydrogel based on Sepineo™ P 600 and Sepineo™ PHD 100 shows optimal application properties. The results obtained provide a basis for further preclinical and clinical studies.

Renal ischemia in the peri-transplant period causes a number of changes that adversely affect the initiation of normal vital functions in grafts after transplantation. To minimise the extent of ischemic damage, organs are stored in preservation fluid. The components of the fluid are supposed to ensure stabilisation of the cell cytoskeleton, protect against oxygen free radicals, reduce cell swelling, and ensure endothelial cell integrity. The aim of this study was to analyse the protective effect of Cu 2+ , as a component of Biolasol preservative fluid, in the prevention of nephron damage occurring during the graft storage period. Analyses of the effectiveness of copper in the presence of prolactin added to Biolasol fluid were also carried out. Forty isolated pig slaughter kidneys were used in the study, avoiding the use of laboratory animals. The kidneys were stored using simple hypothermia. After 2 h and 48 h of graft storage, selected biochemical indicators of renal function were determined in the collected perfusates. The addition of Cu 2+ at a dose of 1 µg/L to the composition of Biolasol fluid was found to affect the generation of ischemic damage in the isolated pig kidney. The intensity of the occurrence of these processes is exacerbated by the presence of prolactin at a dose of 0.1 µg/L.

Insulin loaded to the polymer network of hydrogels may affect the speed and the quality of wound healing in diabetic patients. The aim of our research was to develop a formulation of insulin that could be applied to the skin. We chose hydrogels commonly used for pharmaceutical compounding, which can provide a form of therapy available to every patient. We prepared different gel formulations using Carbopol ® Ultrez TM 10, Carbopol ® Ultrez TM 30, methyl cellulose, and glycerin ointment. The hormone concentration was 1 mg/g of the hydrogel. We assessed the influence of model hydrogels on the pharmaceutical availability of insulin in vitro, and we examined the rheological and the texture parameters of the prepared formulations. Based on spectroscopic methods, we evaluated the influence of model hydrogels on secondary and tertiary structures of insulin. The analysis of rheograms showed that hydrogels are typical of shear-thinning non-Newtonian thixotropic fluids. Insulin release from the formulations occurs in a prolonged manner, providing a longer duration of action of the hormone. The stability of insulin in hydrogels was confirmed. The presence of model hydrogel carriers affects the secondary and the tertiary structures of insulin. The obtained results indicate that hydrogels are promising carriers in the treatment of diabetic foot ulcers. The most effective treatment can be achieved with a methyl cellulose-based insulin preparation.

In this paper, we assess the nephroprotective effects of thyrotropin and follitropin during ischaemia. The studies were performed in vitro in a model of isolated porcine kidneys stored in Biolasol (FZNP, Biochefa, Sosnowiec, Poland) and modified Biolasol (TSH: 1 µg/L; FSH 1 µg/L). We used the static cold storage method. The study was carried out based on 30 kidneys. The kidneys were placed in 500 mL of preservation solution chilled to 4 °C. The samples for biochemical tests were collected during the first kidney perfusion (after 2 h of storage) and during the second perfusion (after 48 h of storage). The results of ALT, AST, and LDH activities confirm the effectiveness of Biolasol + p-TSH in maintaining the structural integrity of renal cell membranes. Significantly reduced biochemical parameters of kidney function, i.e., creatinine and protein concentrations were also observed after 48 h storage. The protective effect of Biasol + p-TSH is most pronounced after 2 h of storage, suggesting a mild course of damage thereafter. A mild deterioration of renal function was observed after 48 h. The results of our analyses did not show any protective effect of Biolasol + p-FSH on the kidneys during ischaemia.

Zinc is an effective anti-inflammatory and antioxidant trace element. The aim of this study was to analyse the protective effect of zinc and zinc-prolactin systems as additives of preservation solutions in the prevention of nephron damage caused during ischemia. The study used a model for storing isolated porcine kidneys in Biolasol ® . The solution was modified with the addition of Zn at a dose of 1 µg/L and Zn: 1 µg/L with prolactin (PRL): 0.1 µg/L. After 2 h and 48 h of storage, the levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, sodium, potassium, creatinine and total protein were determined. Zinc added to the Biolasol ® composition at a dose of 1 µg/L showed minor effectiveness in the protection of nephrons. In turn, Zn 2+ added to Biolasol + PRL (PRL: 0.1 µg/L) acted as a prolactin inhibitor. We do not recommend the addition of Zn(II) (1 µg/L) and Zn(II) (1 µg/L) + PRL (0.1 µg/L) to the Biolasol solution.

Selenium has strong antioxidant properties and diverse effects on the immune system. The aim of the study was to analyse the protective effect of selenium as a component of a kidney preservation solution on the prevention of ischemia-reperfusion injury of nephrons. The solution was modified by the addition of Se (1 µg/L), prolactin (0.1 µg/L) and Se with prolactin (1 µg/L Se + 0.1 µg/L PRL). The study used a model for storing isolated porcine kidneys in Biolasol ® (modified Biolasol ® ), which minimizes ischemia-reperfusion injury of grafts. The introduction of Se 4+ ions at a dose of 1 µg/L into the Biolasol ® preservation solution in the form of Na 2 SeO 3 caused an increase in the activity/concentration of the analysed biochemical parameters: aspartate transaminase, alanine transaminase, urea and protein. This suggests an adverse effect of Se 4+ on nephron function during ischemia-reperfusion. The best graft protection was obtained by using Biolasol ® modified with the addition of selenium (IV) at a dose of 1 µg/L and prolactin at a concentration of 0.1 µg/L. We proposed the mechanism of prolactin action in the metabolic reduction of selenite (SO 3 2- ) during ischemia/reperfusion.

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.

Transplantation is currently a routine method for treating end-stage organ failure. In recent years, there has been some progress in the development of an optimal composition of organ preservation solutions, improving the vital functions of the organ and allowing to extend its storage period until implantation into the recipient. Optimizations are mostly based on commercial solutions, routinely used to store grafts intended for transplantation. The paper reviews hormones with a potential nephroprotective effect, which were used to modify the composition of renal perfusion and preservation solutions. Their effectiveness as ingredients of preservation solutions was analysed based on a literature review. Hormones and trophic factors are innovative preservation solution supplements. They have a pleiotropic effect and affect normal renal function. The expression of receptors for melatonin, prolactin, thyrotropin, corticotropin, prostaglandin E1 and trophic factors was confirmed in the kidneys, which suggests that they are a promising therapeutic target for renal IR (ischemia-reperfusion) injury. They can have anti-inflammatory, antioxidant and anti-apoptotic effects, limiting IR injury.

Corticotropin (ACTH, previously an adrenocorticotropic hormone) is used in the diagnosis and treatment of pituitary gland disorders, adrenal cortex disorders, and other diseases, including autoimmune polymyositis, systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease, and ulcerative colitis. So far, the ointment dosage form containing ACTH for use on the skin is unknown. Therefore, it seems appropriate to develop a semi-solid formulation with corticotropin. Emulsion ointments were prepared using an Unguator based on the cream base Lekobaza ® containing corticotropin in different concentrations, and then the physical and chemical parameters of the ointment formulations, such as pH, spreadability, rheological properties, and texture analysis, were evaluated. In addition, a USP apparatus 2 with enhancer cells was utilized to study the in vitro drug release characteristics of the selected formulations. All the ointments obtained were characterized by good spreadability and viscosity. An analysis of the ointment texture was performed and the dependence of the tested parameters on the ACTH content in the ointment was demonstrated. Examination of the structure of the ointment showed that a high concentration of ACTH increases the hardness and adhesiveness of the ointment. In turn, it adversely affects the cohesiveness and elasticity of the ointments tested. The results of the release study showed that ACTH is released the fastest from the formulation with the lowest concentration, while the slowest from the ointment with the highest concentration of ACTH.