Particle-Assisted Dermal Penetration — A Simple Formulation Strategy to Foster the Dermal Penetration Efficacy

(1) Background: The study systematically investigated the influence of dispersed particles within a topical formulation on the dermal penetration efficacy of active compounds that are dissolved in the water phase of this formulation. The aim was to prove or disprove if particle-assisted dermal penetration can be used for improved dermal drug delivery. (2) Methods: Fluorescein was used as a surrogate for a hydrophilic active ingredient (AI). It was dissolved in the water phase of different formulations with and without particles. Two different types of particles (titanium dioxide and nanostructured lipid carriers (NLC)) were used. The influence of particle size and number of particles and the influence of skin hydrating excipients was also investigated. (3) Results demonstrate that the addition of particles can strongly increase the dermal penetration efficacy of AI. The effect depends on the size of the particles and the number of particles in the formulation, where smaller sizes and higher numbers resulted in higher penetration parameters. Formulations with NLC that contained 20% w/w or 40% w/w particles resulted in an about 2-fold higher amount of penetrated AI and increased the penetration depth about 2.5-fold. The penetration-enhancing effect was highly significant (p [ 0.001) and allowed for an efficient delivery of the AI in the viable dermis. In contrast, the penetration-enhancing effect of excipients that increase the skin hydration was found to be very limited and not significant (�5%, p ] 0.05). (4) Conclusions: Based on the results, it can be concluded that particle-assisted dermal penetration can be considered to be a simple but highly efficient and industrially feasible formulation principle for improved and tailor-made dermal drug delivery of active compounds

Are lipid nanoparticles really superior? A holistic proof of concept study

Lipid nanoparticles are a successful carrier system for dermal drug delivery. They possess various beneficial properties, i.e., increased chemical stability for chemically labile compounds, increased dermal penetration of active compounds, or skin carrying properties after dermal application due to the formation of a so-called 'invisible patch.' Despite manifold studies showing these properties individually, a study that investigates if one lipid nanoparticle formulation can really combine all the above-mentioned benefits at once is not yet available. In the present study, lipid nanoparticles (NLC) were produced and characterized regarding their physico-chemical properties. The chemical stability of the incorporated active ingredient (AI) was determined, as well as the dermal penetration efficacy of the AI, and the skin carrying properties of the NLC after dermal penetration. The properties of the NLC were compared to classical formulations, i.e., AI dissolved in pure oil, an o/w cream base and a nanoemulsion. All formulations contained similar lipids and emulsifiers, which allowed for a direct comparison of the different properties. NLC were shown to provide most efficient chemical stabilization and most efficient dermal penetration for the AI. The formation of the invisible patch was shown for the NLC but not for the other formulations. Skin hydration and skin carrying properties were also most pronounced for the NLC. Results provide evidence that NLC can combine all beneficial effects that were previously described in one formulation. Thus, providing evidence that NLC are a holistically superior formulation principle when compared to other formulation principles

Improved Dermal and Transdermal Delivery of Curcumin with SmartFilms and Nanocrystals

Poor aqueous solubility of active compounds is a major issue in today’s drug delivery. In this study the smartFilm-technology was exploited to improve the dermal penetration efficacy of a poorly soluble active compound (curcumin). Results were compared to the dermal penetration efficacy of curcumin from curcumin bulk suspensions and nanocrystals, respectively. The smartFilms enabled an effective dermal and transdermal penetration of curcumin, whereas curcumin bulk- and nanosuspensions were less efficient when the curcumin content was similar to the curcumin content in the smartFilms. Interestingly, it was found that increasing numbers of curcumin particles within the suspensions increased the passive dermal penetration of curcumin. The effect is caused by an aqueous meniscus that is created between particle and skin if the dispersion medium evaporates. The connecting liquid meniscus causes a local swelling of the stratum corneum and maintains a high local concentration gradient between drug particles and skin. Thus, leading to a high local passive dermal penetration of curcumin. The findings suggest a new dermal penetration mechanism for active compounds from nano-particulate drug delivery systems, which can be the base for the development of topical drug products with improved penetration efficacy in the future

Association between Oral Health-Related Quality of Life in People with Rare Diseases and Their Satisfaction with Dental Care in the Health System of the Federal Republic of Germany

Background: The aim of this study was to examine the current dental care situation in Germany from the perspective of those affected by a rare disease, especially concerning their satisfaction with the German dental health care system, and thus assess the relationship between their perspective and their oral health-related quality of life (OHRQoL). Methods: A questionnaire regarding their experiences with the dental assistance and the health care system, such as the OHIP-14, was sent to the member associations of the organization of self-help groups for rare diseases ACHSE e.V. The correlation between OHIP-14 values and patient’s perspective was statistically analyzed by the non-parametric Tau de Kendall test (p < 0.05). Results: There was a statistically significant correlation between the OHIP score and the patient’s perspective regarding dental assistance and health care system (p < 0.05). For those surveyed who were satisfied with the support of the health care system, an average OHIP score of 8.54 ± 10.45 points (range: 0–48) was determined. The group that did not feel sufficiently supported by the health care system had an average OHIP score of 16.07 ± 13.43 points (range: 0–56). Discussion: The majority of respondents with rare diseases are dissatisfied with the German health care system and its support with regard to dental care

Oral Health-Related Quality of Life in People with Rare Hereditary Connective Tissue Disorders: Marfan Syndrome

Background: The aim of this study was to analyze data on oral health-related quality of life (OHRQoL) in people with Marfan syndrome and to obtain information on the diagnosis period, orthodontic treatment, and oral symptoms. Methods: A questionnaire was developed consisting of open questions and the standardized German version of the OHIP-14 (Oral Health Impact Profile) questionnaire for the evaluation of OHRQoL. The age of diagnosis, time period from the first signs of the disease to diagnosis, and OHIP-values were compared between male and female participants. Additionally, the OHIP-values between participants who were orthodontically treated and those who were not treated were assessed. The statistical analysis was performed using the Mann⁻Whitney test with a significance level at p = 0.05. Results: A total of 51 questionnaires were evaluated, which included 34 female and 17 male participants. Overall, 84% of respondents reported oral symptoms. Male respondents tended to diagnose the disease earlier (p = 0.00), with a smaller period between the first symptom and the diagnosis (p = 0.04). The OHIP-14 score was gender-neutral at 13.65 ± 13.53 points. Conclusion: In Marfan syndrome, many years (12.01 ± 11.61) elapse between the onset of first symptoms and correct diagnosis of the disease. People with Marfan syndrome have a worse OHRQoL than do the general population

Fingerprint of Nature—Skin Penetration Analysis of a Stinging Nettle PlantCrystals Formulation

Background: PlantCrystals are a new concept to produce plant-based formulations. Their principle is based on the diminution of parts of or whole plants. In this study, the effect of a surfactant on stinging nettle leaf PlantCrystals was investigated. Secondly, the contents of bulk material and the PlantCrystals formulation were compared. In addition, for the very first time, the skin penetration of PlantCrystals was investigated. Methods: Stinging nettle leaves were milled with high-pressure homogenization. Sizes were analyzed via light microscopy and static light scattering. To investigate the effect of the milling, the flavonoid and total carotenoid content were determined, and the antioxidant capacity of the formulation was measured via total polyphenol content and DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. Finally, the impact on skin penetration was investigated. Results: Size analysis showed a stabilizing effect of the surfactant, and the chemical analysis revealed higher flavonoid and polyphenol contents for PlantCrystals. The penetration of the formulation into the stratum corneum was shown to be promising; PlantCrystals possessed a visually perceived higher fluorescence and homogeneity compared to the bulk material. Conclusion: The concept of PlantCrystals improved the availability of valuable constituents and the penetration efficacy. The utilization of the natural chlorophyll fluorescence for skin penetration analysis of plant-based formulations proved itself highly effective

Oral Symptoms and Oral Health-Related Quality of Life in People with Rare Diseases in Germany: A Cross-Sectional Study

Background: The aim of this study was to collect information on oral health-related quality of life (OHRQoL) in people with rare diseases. Methods: A questionnaire comprising free text questions and the German version of the standardized Oral Health Impact Profile-14 (OHIP-14) questionnaire on OHRQoL was developed. All participants who indicated oral symptoms in the questionnaire were included in a cluster analysis. Different cluster analyses were performed (Ward’s, k-Means) to find symptom profile groups in the data. Results: A total of 484 questionnaires with 96 rare diseases were included in the study. The most reported symptoms were anomalies of the tooth formation, dysgnathia, changes in number of the teeth, and malocclusions. The OHIP mean values of the five resulting symptom clusters ranged from 15.1 to 19.9, which is very high compared to the general population in Germany, which has a mean value of 4.09. Discussion: All investigated symptoms show a negative association with OHRQoL, but the strongest were for symptoms of the oral mucosa and periodontal diseases. All the symptoms described in this cluster analysis can lead to considerably higher mean values of the OHIP total score among people with rare disease and thus to worse OHRQoL than reported in the general population

Transfer of the Experimental Autoimmune Glaucoma Model from Rats to Mice—New Options to Study Glaucoma Disease

Studies have suggested an involvement of the immune system in glaucoma. Hence, a rat experimental autoimmune glaucoma model (EAG) was developed to investigate the role of the immune response. Here, we transferred this model into mice. Either 0.8 mg/mL of the optic nerve antigen homogenate (ONA; ONA 0.8) or 1.0 mg/mL ONA (ONA 1.0) were injected in 129/Sv mice. Controls received sodium chloride. Before and 6 weeks after immunization, the intraocular pressure (IOP) was measured. At 6 weeks, retinal neurons, glia cells, and synapses were analyzed via immunohistology and quantitative real-time PCR (RT-qPCR). Additionally, optic nerves were examined. The IOP stayed in the normal physiological range throughout the study (p > 0.05). A significant reduction of retinal ganglion cells (RGCs) was noted in both immunized groups (p < 0.001). Remodeling of glutamatergic and GABAergic synapses was seen in ONA 1.0 retinas. Furthermore, both ONA groups revealed optic nerve degeneration and macrogliosis (all: p < 0.001). An increase of activated microglia was noted in ONA retinas and optic nerves (p < 0.05). Both ONA concentrations led to RGC loss and optic nerve degeneration. Therefore, the EAG model was successfully transferred from rats to mice. In further studies, transgenic knockout mice can be used to investigate the pathomechanisms of glaucoma more precisely

Methodology to Reach Full Spectral Photo-Protection by Selecting the Best Combination of Physical Filters and Antioxidants

Antioxidants can reduce free radical formation in deeper skin layers where typical sunscreen filters may no longer be effective. Here, a general method is presented to pre-select optimum combinations of antioxidants and physical filters. The radical production of selected common physical filters after UV irradiation, the capacity of different antioxidants and the interaction between these compounds was investigated in solution by optical measurement of DPPH scavenging, allowing a theoretical calculation of the antioxidant amount necessary to scavenge UV-induced radicals. Furthermore, the antioxidant capacity and the scattering properties were determined. All physical filters induced different amounts of radicals in suspensions depending on the coating. ZnO coated with polydimethylsiloxane and myristic acid (ZnOpolymyr) showed the lowest radical formation. Epigallocatechin-gallate (EGCG) provided the highest antioxidant capacity. Different formulations with different ratios of selected physical filters and antioxidants were prepared. It turned out that the high radical protection factor (RPF) of cream formulations, which originally did not contain any physical filters, was reduced when such filters were added. The data demonstrates that the addition of physical filters to antioxidant-containing formulations lowers their reduction capacity, but to varying degrees. An optimal combination of physical filters and antioxidants must be pre-selected in order to incorporate them into a formulation and verify their effect on skin

Methodology to Reach Full Spectral Photo-Protection by Selecting the Best Combination of Physical Filters and Antioxidants

Antioxidants can reduce free radical formation in deeper skin layers where typical sunscreen filters may no longer be effective. Here, a general method is presented to pre-select optimum combinations of antioxidants and physical filters. The radical production of selected common physical filters after UV irradiation, the capacity of different antioxidants and the interaction between these compounds was investigated in solution by optical measurement of DPPH scavenging, allowing a theoretical calculation of the antioxidant amount necessary to scavenge UV-induced radicals. Furthermore, the antioxidant capacity and the scattering properties were determined. All physical filters induced different amounts of radicals in suspensions depending on the coating. ZnO coated with polydimethylsiloxane and myristic acid (ZnOpolymyr) showed the lowest radical formation. Epigallocatechin-gallate (EGCG) provided the highest antioxidant capacity. Different formulations with different ratios of selected physical filters and antioxidants were prepared. It turned out that the high radical protection factor (RPF) of cream formulations, which originally did not contain any physical filters, was reduced when such filters were added. The data demonstrates that the addition of physical filters to antioxidant-containing formulations lowers their reduction capacity, but to varying degrees. An optimal combination of physical filters and antioxidants must be pre-selected in order to incorporate them into a formulation and verify their effect on skin