Microemulsions as Solubilizers and Penetration Enhancers for Minoxidil Release from Gels

Micro- and nanoemulsions are potential drug solubilizers and penetration enhancers through the high surfactant/co-surfactant content. This study aimed to evaluate the influence of minoxidil (MXD) solubilized in the microemulsions (MEs) on drug release by in vitro/ex vivo diffusion through the semi-permeable membrane Spectra/Por® (Spectrum Laboratory, Gardena, CA, USA) and porcine ear skin. Moreover, a residual amount of drug in the skin after ex vivo diffusion was evaluated. The reference MER, lecithin-containing MEL, and gelatin-containing MEG were characterized in terms of their size, polydispersity index, density, viscosity, electrical conductivity and surface tension. Based on the in vitro diffusion, it can be argued that MEL slowed down the drug release, while MER and MEG have no significant effect compared to the sample, in which propylene glycol (PG) was used as a solubilizer. Determination of the residual drug amount in the skin after 6 h of the ex vivo permeation was demonstrated as the most valuable method to evaluate the effectiveness of the ME’s application. The results indicate that the most optimal MXD permeation enhancers in alginate gel were the natural surfactants containing MEs. MXD solubilization in MEG and MEL had caused more than 5% of the drug remaining in the skin, which is almost a 1.5-fold higher amount compared to the reference gel

Microemulsions as Solubilizers and Penetration Enhancers for Minoxidil Release from Gels

Micro- and nanoemulsions are potential drug solubilizers and penetration enhancers through the high surfactant/co-surfactant content. This study aimed to evaluate the influence of minoxidil (MXD) solubilized in the microemulsions (MEs) on drug release by in vitro/ex vivo diffusion through the semi-permeable membrane Spectra/Por® (Spectrum Laboratory, Gardena, CA, USA) and porcine ear skin. Moreover, a residual amount of drug in the skin after ex vivo diffusion was evaluated. The reference MER, lecithin-containing MEL, and gelatin-containing MEG were characterized in terms of their size, polydispersity index, density, viscosity, electrical conductivity and surface tension. Based on the in vitro diffusion, it can be argued that MEL slowed down the drug release, while MER and MEG have no significant effect compared to the sample, in which propylene glycol (PG) was used as a solubilizer. Determination of the residual drug amount in the skin after 6 h of the ex vivo permeation was demonstrated as the most valuable method to evaluate the effectiveness of the ME’s application. The results indicate that the most optimal MXD permeation enhancers in alginate gel were the natural surfactants containing MEs. MXD solubilization in MEG and MEL had caused more than 5% of the drug remaining in the skin, which is almost a 1.5-fold higher amount compared to the reference gel

Combination Therapy of Carnosic Acid and Methotrexate Effectively Suppressed the Inflammatory Markers and Oxidative Stress in Experimental Arthritis

Background: Combination therapy with methotrexate (MTX) is the most common therapeutic strategy used for the treatment of patients with rheumatoid arthritis (RA). In this study, we combined the natural compound carnosic acid (CA) with MTX to reduce inflammation and oxidative stress in adjuvant arthritis (AA). Methods: AA was induced in 6–8 rats per group. MTX was administrated twice a week at a dose of 0.3 mg/kg b.w., while CA was administered daily at a dose of 100 mg/kg both in monotherapy and in combination with MTX. Plasma samples were collected on the 14th, 21st, and 28th day. Body weight and hind paw volume were measured once a week. Results: We found that, mainly, the CA + MTX combination significantly reduced the hind paw swelling, the levels of IL-17A, MMP-9, and MCP-1 in plasma, and GGT activity in joint homogenates. The mRNA expression of HO-1, catalase, and IL-1β in the liver were significantly improved by CA + MTX only. Our results indicate that adding CA to MTX treatment could be a good therapeutic option for patients suffering from RA. Conclusions: The addition of CA to methotrexate treatment significantly improved its efficacy in decreasing the development of AA by inhibiting the markers of inflammation and oxidative stress

Bioflavonoid Robinin from Astragalus falcatus Lam. Mildly Improves the Effect of Metothrexate in Rats with Adjuvant Arthritis

Anti-inflammatory potential of orally administrated bioflavonoid-robinin, active sub-stance of original drug Flaroninum™ (FL), was investigated in the combination with methotrexate (MTX) and in monotherapy in rats suffering from adjuvant-induced arthritis (AA). Robinin (kaempferol-3-O-robinoside-7-O-rhamnoside) was isolated from the aerial parts of Astragalus falcatus Lam. The monotherapy with robinin was not efficient in alleviating symptoms of AA. The combination of MTX with robinin was similarly active as MTX alone in reducing the hind paw volume and change of body weight during the whole experiment. The combination, however, reduced plasma levels of Interleukin-17Aand activity of gamma-glutamyl transferase in joint more efficiently then MTX alone. Our results demonstrate that the novel combination of robinin and MTX mildly improved the reduction of inflammation in experimental arthritis

Enhanced Anti-Inflammatory Effect of the Combination of Lactiplantibacillus plantarum LS/07 with Methotrexate Compared to Their Monotherapies Studied in Experimental Arthritis

The gut microbiome (GM) of rheumatic arthritis (RA) patients is often altered in composition and function. Moreover, methotrexate (MTX), one of the most frequently used disease-modifying antirheumatic drugs, is known to negatively affect GM composition. The modulation of immune system activity is one of the therapeutic benefits of probiotics. The aim of the current investigation was to determine the impact of MTX therapy combined with one of the Lactobacillus strains, Lactoplantibacillus plantarum LS/07 (LB), on adjuvant arthritis (AA) in rats. Methods focused on biometric and inflammatory parameters in AA, particularly on plasmatic levels of IL-17A, MMP-9, and MCP-1, and the activities of gamma-glutamyl transferase in the spleen and joints were applied. Enhancing the effect of MTX, LB positively influenced all biometric and inflammatory parameters. The findings of the present study may be of help in proposing novel therapeutic strategies for RA patients

Effect of N-Feruloylserotonin and Methotrexate on Severity of Experimental Arthritis and on Messenger RNA Expression of Key Proinflammatory Markers in Liver

Rheumatoid arthritis (RA) is a chronic inflammatory disease, leading to progressive destruction of joints and extra-articular tissues, including organs such as liver and spleen. The purpose of this study was to compare the effects of a potential immunomodulator, natural polyphenol N-feruloylserotonin (N-f-5HT), with methotrexate (MTX), the standard in RA therapy, in the chronic phase of adjuvant-induced arthritis (AA) in male Lewis rats. The experiment included healthy controls (CO), arthritic animals (AA), AA given N-f-5HT (AA-N-f-5HT), and AA given MTX (AA-MTX). N-f-5HT did not affect the body weight change and clinical parameters until the 14th experimental day. Its positive effect was rising during the 28-day experiment, indicating a delayed onset of N-f-5HT action. Administration of either N-f-5HT or MTX caused reduction of inflammation measured as the level of CRP in plasma and the activity of LOX in the liver. mRNA transcription of TNF-α and iNOS in the liver was significantly attenuated in both MTX and N-f-5HT treated groups of arthritic rats. Interestingly, in contrast to MTX, N-f-5HT significantly lowered the level of IL-1β in plasma and IL-1β mRNA expression in the liver and spleen of arthritic rats. This speaks for future investigations of N-f-5HT as an agent in the treatment of RA in combination therapy with MTX