Cutibacterium acnes induces acne-like lesions in hairless mice models - A comparative study.

Acne vulgaris, a chronic inflammatory skin disease with a high prevalence worldwide, necessitates reliable preclinical models for both understanding its pathogenesis and evaluating potential anti-acne therapies. This study aims to establish a robust mouse model using intracutaneous injection of Cutibacterium acnes bacterial suspension. Three hairless mouse strains (SKH-hr1, SKH-hr2 brown, and SKH-hr2 + ApoE) were systematically compared to ascertain the stains most closely resembling acne in humans. Various assessments, including photo documentation, biophysical evaluation, blood analysis, and histopathology, were conducted. Despite all strains exhibiting acne-like lesions, SKH-hr1 mice emerged as the most suitable model, demonstrating the most satisfactory results across multiple criteria. This research underscores the significance of employing hairless mice strains as models in acne studies to enhance and facilitate the development of effective therapeutic interventions.

Scanning electron microscopy study on nanoemulsions and solid lipid nanoparticles containing high amounts of ceramides.

Ceramides are the most important intercellular lipids of the stratum corneum, regulating the barrier function of the skin and participating as second signal messenger in stress-induced apoptosis. The high lipophilicity of ceramides presents a pharmacological problem. In order to overcome this problem two lipophilic delivery systems were used for the incorporation of the ceramides: (1) nanoemulsions (NE) and (2) solid lipid nanoparticles (SLN). The influence of the incorporation of ceramides on the particle shape, size and Polydispersity Index was investigated by photon correlation spectroscopy (PCS) and scanning electron microscopy (SEM). The results showed that NE can incorporate larger amounts of ceramides than SLN (up to 23.2% and 5% of lipid matrix, respectively) without any significant alteration on the morphology of the dispersed particles. The incorporation of higher amounts of ceramides into SLN, leads to anisometric platelet-like formations that are known to be caused by the transition of triglycerides from alpha- to beta-mesomorph. The results of this study can be useful for the design of appropriate delivery systems and for further pharmacological evaluations.

Rapid alterations of serum oxidant and antioxidant status with the intravenous administration of n-6 polyunsaturated fatty acids.

In an attempt to achieve the safe intravenous administration of two n-6 polyunsaturated fatty acids (PUFAs), gamma-linolenic acid (GLA) and arachidonic acid (AA), and to study the subsequent changes on the total oxidant and antioxidant status, various steadily increasing doses of each acid were injected intravenously at different infusion times in 28 male rabbits. Blood samples were collected at 15-min time intervals by the hepatic veins and from the carotid artery; oxidant status was determined by the thiobarbiturate assay and total antioxidant status (TAS) was assessed by a colorimetric assay. Both n-6 PUFAs were administered with safety at a dose of 25 mg/kg within 10 min accompanied by an increase of malonodialdehyde concentrations in the hepatic veins and in the carotid artery 30-45 min, respectively, after the end of the infusion of GLA and/or AA. Similar changes did not occur in red cell membranes after the infusion of AA. TAS presented reciprocal changes to malonodialdehyde production; the main consumption of TAS was observed in all samples 30-60 min after the end of the infusion of n-6 PUFAs. The above-mentioned rapid alterations occurring in both serum oxidant and antioxidant status after GLA might have a future clinical therapeutic significance in conditions like cancer and disseminated infectious diseases.

In-vitro cytotoxic/cytostatic activity of anionic liposomes containing vinblastine against leukaemic human cell lines.

Liposomes prepared from lipids dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) with cholesterol were used to investigate the percentage of vinblastine encapsulation and the influence of lipid composition on the retention properties of vinblastine in buffer as well as in cell culture medium. Differential scanning calorimetry (DSC) was applied, to study the effect of cholesterol on the phase transition temperature and on the AH of the two liposome formulations. The cytotoxic and cytostatic activity of the liposome-encapsulated vinblastine was also examined against six leukaemic human cell lines. The results showed that encapsulation of vinblastine into liposomes was greater than 98% with a drug-phospholipid molar ratio of 0.13-0.18. The major improvement in vinblastine retention in buffer as well as in culture medium was achieved by employing DPPG. The DSC data showed that vinblastine exerted a more perturbing effect in DPPC-cholesterol bilayers than in DPPG-cholesterol bilayers and this may explain their lower retention time. The 50% growth-inhibiting (GI50) and cytostatic (TGI) activity of liposomal vinblastine did not seem to be affected by the type of the liposome while the 50% cytotoxic activity (LC50) was affected in four out of the six cell lines tested. The parameters GI50, TGI and LC50 were estimated according to the instructions given by the NCI.