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Lipid nanoparticles (LN) were invented in the early 1990ties and can be exploited for oral and topical drug delivery to increase the bioavailability of lipophilic active compounds. The lipid matrix of the LN can be composed of solid lipids or of a mixture of liquid and solid lipids. The influence of the lipid matrix composition of LN on the dermal penetration efficacy is not known and was therefore investigated in this study. For this the whole spectrum of LN, that means NE (100% liquid lipid), SLN (100% solid lipid) and NLC that contained low, medium and high amounts of oil were produced and characterized in regard to size, zeta potential, crystallinity and in-vitro release. In addition, the dermal penetration efficacy was determined ex-vivo and the bio-physical skin parameters, i.e., spreadability on skin, skin hydration, skin friction and transepidermal water loss were also assessed. Results demonstrate the tremendous influence of the lipid matrix composition on the biopharmaceutical properties of the LN but showed only minor differences in the physico-chemical properties of the particles. The physico-chemical properties of the LN and the in-vitro release data were not clearly linked to the dermal penetration efficacy, because also other parameters, e.g., skin hydration, spreadability of the formulation on skin and/or film formation of the LN on skin were found to be important parameters that influence the dermal penetration efficacy. Therefore, to allow for the development of effective LN formulations with tailor-made biopharmaceutical properties, not only the physico-chemical properties and in-vitro drug release profiles but also the most relevant biopharmaceutical properties of the LN should be assessed during the formulation development of LN.
Cornelia M. Keck; David Specht; Jana Brüßler. Influence of lipid matrix composition on biopharmaceutical properties of lipid nanoparticles. Journal of Controlled Release 2021, 338, 149 -163.
AMA StyleCornelia M. Keck, David Specht, Jana Brüßler. Influence of lipid matrix composition on biopharmaceutical properties of lipid nanoparticles. Journal of Controlled Release. 2021; 338 ():149-163.
Chicago/Turabian StyleCornelia M. Keck; David Specht; Jana Brüßler. 2021. "Influence of lipid matrix composition on biopharmaceutical properties of lipid nanoparticles." Journal of Controlled Release 338, no. : 149-163.
Mitochondrial dysfunction represents a hallmark of both brain aging and age-related neurodegenerative disorders including Alzheimer disease (AD). AD-related mitochondrial dysfunction is characterized by an impaired electron transport chain (ETC), subsequent decreased adenosine triphoshpate (ATP) levels, and elevated generation of reactive oxygen species (ROS). The bioactive citrus flavanone hesperetin (Hst) is known to modulate inflammatory response, to function as an antioxidant, and to provide neuroprotective properties. The efficacy in improving mitochondrial dysfunction of Hst nanocrystals (HstN) with increased bioavailability has not yet been investigated. Human SH-SY5Y cells harboring neuronal amyloid precursor protein (APP695) acted as a model for the initial phase of AD. MOCK-transfected cells served as controls. The energetic metabolite ATP was determined using a luciferase-catalyzed bioluminescence assay. The activity of mitochondrial respiration chain complexes was assessed by high-resolution respirometry using a Clarke electrode. Expression levels of mitochondrial respiratory chain complex genes were determined using quantitative real-time polymerase chain reaction (qRT-PCR). The levels of amyloid β-protein (Aβ1-40) were measured using homogeneous time-resolved fluorescence (HTRF). ROS levels, peroxidase activity, and cytochrome c activity were determined using a fluorescence assay. Compared to pure Hst dissolved in ethanol (HstP), SH-SY5Y-APP695 cells incubated with HstN resulted in significantly reduced mitochondrial dysfunction: ATP levels and respiratory chain complex activity significantly increased. Gene expression levels of RCC I, IV, and V were significantly upregulated. In comparison, the effects of HstN on SY5Y-MOCK control cells were relatively small. Pure Hst dissolved in ethanol (HstP) had almost no effect on both cell lines. Neither HstN nor HstP led to significant changes in Aβ1-40 levels. HstN and HstP were both shown to lower peroxidase activity significantly. Furthermore, HstN significantly reduced cytochrome c activity, whereas HstP had a significant effect on reducing ROS in SH-SY5Y-APP695 cells. Thus, it seems that the mechanisms involved may not be linked to altered Aβ production. Nanoflavonoids such as HstN have the potential to prevent mitochondria against dysfunction. Compared to its pure form, HstN showed a greater effect in combatting mitochondrial dysfunction. Further studies should evaluate whether HstN protects against age-related mitochondrial dysfunction and thus may contribute to late-onset AD.
Lukas Babylon; Rekha Grewal; Pascal-L. Stahr; Ralph Eckert; Cornelia Keck; Gunter Eckert. Hesperetin Nanocrystals Improve Mitochondrial Function in a Cell Model of Early Alzheimer Disease. Antioxidants 2021, 10, 1003 .
AMA StyleLukas Babylon, Rekha Grewal, Pascal-L. Stahr, Ralph Eckert, Cornelia Keck, Gunter Eckert. Hesperetin Nanocrystals Improve Mitochondrial Function in a Cell Model of Early Alzheimer Disease. Antioxidants. 2021; 10 (7):1003.
Chicago/Turabian StyleLukas Babylon; Rekha Grewal; Pascal-L. Stahr; Ralph Eckert; Cornelia Keck; Gunter Eckert. 2021. "Hesperetin Nanocrystals Improve Mitochondrial Function in a Cell Model of Early Alzheimer Disease." Antioxidants 10, no. 7: 1003.
Oxidative stress diseases are usually treated or prevented by using antioxidants from natural or artificial sources. However, as a sustainable source of phytochemicals, plants got a renewed interest in obtaining their active agents using green extraction technologies, i.e., sustainable extraction techniques that reduce energy consumption, use renewable sources and result in less post-extraction wastes. The high-pressure homogenization (HPH) technique was introduced into the food industry since it was invented in 1900 to homogenize milk and later to produce fruit juices with a longer shelf-life without preservatives. Recently, HPH was introduced as an eco-friendly method to nanomill plants for improved extraction efficacy without using organic solvents. In this study, sumac was used as an antioxidants-rich spice model to investigate the effects of HPH on its antioxidant capacity (AOC). Sumac was rendered into PlantCrystals by using HPH. Particle size characterization proved the presence of submicron-sized particles (about 750 nm). Thus, HPH was able to produce sumac PlantCrystals and increased the AOC of bulk sumac by more than 650% according to the ORAC (oxygen radical absorbance capacity) assay. The polyphenol and flavonoid contents showed higher values after HPH. Interestingly, the DPPH (1,1-diphenyl-2-picrylhydrazyl) assay also showed a well improved AOC (similar to ascorbic acid) after HPH. In fact, in this study, the PlantCrystal-technology was demonstrated to cause an efficient cell rupture of the sumac plant cells. This caused an efficient release of antioxidants and resulted in sumac PlantCrystals with a 6.5-fold higher antioxidant capacity when compared to non-processed sumac bulk material.
Abraham Abraham; Camilo Quintero; Luis Carrillo-Hormaza; Edison Osorio; Cornelia Keck. Production and Characterization of Sumac PlantCrystals: Influence of High-Pressure Homogenization on Antioxidant Activity of Sumac (Rhus coriaria L.). Plants 2021, 10, 1051 .
AMA StyleAbraham Abraham, Camilo Quintero, Luis Carrillo-Hormaza, Edison Osorio, Cornelia Keck. Production and Characterization of Sumac PlantCrystals: Influence of High-Pressure Homogenization on Antioxidant Activity of Sumac (Rhus coriaria L.). Plants. 2021; 10 (6):1051.
Chicago/Turabian StyleAbraham Abraham; Camilo Quintero; Luis Carrillo-Hormaza; Edison Osorio; Cornelia Keck. 2021. "Production and Characterization of Sumac PlantCrystals: Influence of High-Pressure Homogenization on Antioxidant Activity of Sumac (Rhus coriaria L.)." Plants 10, no. 6: 1051.
Introduction: Curcumin is a promising drug candidate, but its use for dermal application is limited due to its poor aqueous solubility. Thus, formulations that increase the solubility of curcumin are needed to fully exploit the therapeutic potential of curcumin. Various previous studies address this issue, but a comparison of the efficacy between these formulations remains difficult. The reason for this is a missing standard formulation as benchmark control and an easy-to-use skin penetration model that allows for a fast discrimination between different formulations. Objective: Thus, the aims of this study were the development of a curcumin standard formulation and a screening tool that allows for a fast discrimination between the dermal penetration efficacies of curcumin from different formulations. Methods: Ethanolic curcumin solutions were selected as simple and easy to produce standard formulations, and the ex vivo porcine ear model, coupled with epifluorescence microscopy and subsequent digital image analysis, was utilized to determine the dermal penetration efficacy of curcumin from the different formulations. Results: Results show that the utilized skin penetration model is a suitable and versatile tool that enables not only a fast determination of the dermal penetration efficacy of curcumin from different formulations but also a detailed and mechanistic information on the fate of chemical compounds after dermal penetration. Ethanolic solutions containing 0.25% curcumin were found to be the most suitable standard formulation. Conclusions: Results of the study provide a new, effective screening tool for the development of dermal formulations for improved dermal delivery of curcumin.
Olga Pelikh; Shashank R. Pinnapireddy; Cornelia M. Keck. Dermal Penetration Analysis of Curcumin in an ex vivo Porcine Ear Model Using Epifluorescence Microscopy and Digital Image Processing. Skin Pharmacology and Physiology 2021, 34, 1 -19.
AMA StyleOlga Pelikh, Shashank R. Pinnapireddy, Cornelia M. Keck. Dermal Penetration Analysis of Curcumin in an ex vivo Porcine Ear Model Using Epifluorescence Microscopy and Digital Image Processing. Skin Pharmacology and Physiology. 2021; 34 (3):1-19.
Chicago/Turabian StyleOlga Pelikh; Shashank R. Pinnapireddy; Cornelia M. Keck. 2021. "Dermal Penetration Analysis of Curcumin in an ex vivo Porcine Ear Model Using Epifluorescence Microscopy and Digital Image Processing." Skin Pharmacology and Physiology 34, no. 3: 1-19.
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.
Ralph Eckert; Sabrina Wiemann; Cornelia Keck. Improved Dermal and Transdermal Delivery of Curcumin with SmartFilms and Nanocrystals. Molecules 2021, 26, 1633 .
AMA StyleRalph Eckert, Sabrina Wiemann, Cornelia Keck. Improved Dermal and Transdermal Delivery of Curcumin with SmartFilms and Nanocrystals. Molecules. 2021; 26 (6):1633.
Chicago/Turabian StyleRalph Eckert; Sabrina Wiemann; Cornelia Keck. 2021. "Improved Dermal and Transdermal Delivery of Curcumin with SmartFilms and Nanocrystals." Molecules 26, no. 6: 1633.
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.
Daniel Knoth; Reem Alnemari; Sabrina Wiemann; Cornelia Keck; Jana Brüßler. Fingerprint of Nature—Skin Penetration Analysis of a Stinging Nettle PlantCrystals Formulation. Cosmetics 2021, 8, 21 .
AMA StyleDaniel Knoth, Reem Alnemari, Sabrina Wiemann, Cornelia Keck, Jana Brüßler. Fingerprint of Nature—Skin Penetration Analysis of a Stinging Nettle PlantCrystals Formulation. Cosmetics. 2021; 8 (1):21.
Chicago/Turabian StyleDaniel Knoth; Reem Alnemari; Sabrina Wiemann; Cornelia Keck; Jana Brüßler. 2021. "Fingerprint of Nature—Skin Penetration Analysis of a Stinging Nettle PlantCrystals Formulation." Cosmetics 8, no. 1: 21.
· Background: Oxidative stress diseases are usually treated or prevented by using antioxidants from natural or artificial sources. However, as a sustainable source of phytochemicals, plants got a renewed interest in obtaining their active agents using green technologies. Green chemistry is the ability to obtain commercially viable products with desirable properties from widely available renewable sources using eco-friendly methods. The high-pressure homogenization (HPH) technique was introduced into the food industry since it was invented in 1900 to homogenize milk and later to produce fruit juices with a longer shelf-life without preservatives. Recently, HPH was introduced as an eco-friendly method to nano mill plants for improved extraction efficacy without using organic solvents. ·Results: In this study, sumac was used as an antioxidants-rich spice model to investigate the effects of HPH on its antioxidant capacity (AOC). Sumac was rendered into PlantCrystals by using HPH. Particle size characterization proved the presence of submicron-sized particles (about 750 nm). Thus, HPH was able to produce sumac PlantCrystals and increase the AOC of bulk sumac by more than 500% according to the ORAC (oxygen radical absorbance capacity) assay. The polyphenol and flavonoid contents showed higher values after HPH. Interestingly, the DPPH (1,1-diphenyl-2-picrylhydrazyl) assay also showed a well improved AOC (similar to ascorbic acid) after HPH. · Conclusion: In fact, in this study, the great potential of the green PlantCrystal-technology could be demonstrated.
Abraham M. Abraham; Camilo Quintero; Luis Carrillo-Hormaza; Edison Osorio; Cornelia M Keck. Production and Characterization Of Sumac Plantcrystals: Influence of High-Pressure Homogenization on Antioxidant Activity of Sumac (Rhus Coriaria L.). 2021, 1 .
AMA StyleAbraham M. Abraham, Camilo Quintero, Luis Carrillo-Hormaza, Edison Osorio, Cornelia M Keck. Production and Characterization Of Sumac Plantcrystals: Influence of High-Pressure Homogenization on Antioxidant Activity of Sumac (Rhus Coriaria L.). . 2021; ():1.
Chicago/Turabian StyleAbraham M. Abraham; Camilo Quintero; Luis Carrillo-Hormaza; Edison Osorio; Cornelia M Keck. 2021. "Production and Characterization Of Sumac Plantcrystals: Influence of High-Pressure Homogenization on Antioxidant Activity of Sumac (Rhus Coriaria L.)." , no. : 1.
Background: Vegetables and fruits are consumed in considerable amounts worldwide producing huge quantities of organic leftovers comprising primarily of peels. Peels of potatoes (PP) and carrots (CP), for instance, are often considered as waste, albeit they still represent a rich source of interesting phytochemicals. Traditional waste management of such materials, usually vermicomposting, therefore represents a low-value approach and also a considerable burden to the environment. Objective: Aiming to convert some of this waste into raw materials for further applications, methods were explored to prepare suspensions of PP and CP. Antioxidant activities of these suspensions were compared to bulk-suspensions and the corresponding ethanolic extracts in anticipation of possible applications in Nutrition and Cosmetics. Methods: The peels of potatoes and carrots were subjected to high- speed stirring (HSS) and highpressure homogenization (HPH) to produce suspensions which were characterized for size distribution by Laser Diffraction (LD), Photon Correlation Spectroscopy (PCS), and light microscopy (LM). Ethanolic extracts of peels were also produced. Samples were evaluated for antioxidant activity employing 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Results: HPH produced suspensions of peels comprising particles with diameters in the range of 268 - 335 nm for PP and 654 - 1,560 nm for CP. These suspensions exhibited a significantly stronger antioxidant activity compared to the bulk-suspensions. Moreover, the suspension of PP (1% w/w) exhibited comparable antioxidant activity to the ethanolic extract (1% w/w) whilst the CP suspension (1% w/w) exhibited lower activity compared to the ethanolic extract. Conclusion: Production of suspensions of vegetable peels may unlock some biological potential which could be optimised for applications in Nutrition, Agriculture, Medicine and Cosmetics.
Dalia A. Yassin; Muhammad Jawad Nasim; Abraham M. Abraham; Cornelia M. Keck; Claus Jacob. Upcycling Culinary Organic Waste: Production of Plant Particles from Potato and Carrot Peels to Improve Antioxidative Capacity. Current Nutraceuticals 2021, 2, 62 -70.
AMA StyleDalia A. Yassin, Muhammad Jawad Nasim, Abraham M. Abraham, Cornelia M. Keck, Claus Jacob. Upcycling Culinary Organic Waste: Production of Plant Particles from Potato and Carrot Peels to Improve Antioxidative Capacity. Current Nutraceuticals. 2021; 2 (1):62-70.
Chicago/Turabian StyleDalia A. Yassin; Muhammad Jawad Nasim; Abraham M. Abraham; Cornelia M. Keck; Claus Jacob. 2021. "Upcycling Culinary Organic Waste: Production of Plant Particles from Potato and Carrot Peels to Improve Antioxidative Capacity." Current Nutraceuticals 2, no. 1: 62-70.
Antioxidants are recommended to prevent and treat oxidative stress diseases. Plants are a balanced source of natural antioxidants, but the poor solubility of plant active molecules in aqueous media can be a problem for the formulation of pharmaceutical products. The potential of PlantCrystal technology is known to improve the extraction efficacy and antioxidant capacity (AOC) of different plants. However, it is not yet proved for plant waste. Black tea (BT) infusion is consumed worldwide and thus a huge amount of waste occurs as a result. Therefore, BT waste was recycled into PlantCrystals using small-scale bead milling. Their characteristics were compared with the bulk-materials and tea infusion, including particle size and antioxidant capacity (AOC) in-vitro. Waste PlantCrystals possessed a size of about 280 nm. Their AOC increased with decreasing size according to the DPPH (1,1-diphenyl-2-picrylhydrazyl) and ORAC (oxygen radical absorbance capacity) assays. The AOC of the waste increased about nine-fold upon nanonization, leading to a significantly higher AOC than the bulk-waste and showed no significant difference to the infusion and the used standard according to DPPH assay. Based on the results, it is confirmed that the PlantCrystal technology represents a natural, cost-effective plant-waste recycling method and presents an alternative source of antioxidant phenolic compounds.
Abraham Abraham; Reem Alnemari; Jana Brüßler; Cornelia Keck. Improved Antioxidant Capacity of Black Tea Waste Utilizing PlantCrystals. Molecules 2021, 26, 592 .
AMA StyleAbraham Abraham, Reem Alnemari, Jana Brüßler, Cornelia Keck. Improved Antioxidant Capacity of Black Tea Waste Utilizing PlantCrystals. Molecules. 2021; 26 (3):592.
Chicago/Turabian StyleAbraham Abraham; Reem Alnemari; Jana Brüßler; Cornelia Keck. 2021. "Improved Antioxidant Capacity of Black Tea Waste Utilizing PlantCrystals." Molecules 26, no. 3: 592.
Poor aqueous solubility of drug substances is associated with poor bioavailability and thus hampers the effective use of many potent active pharmaceutical ingredients. Various strategies to overcome poor solubility are available, whereby drug nanocrystals represent one of the most powerful formulation strategies to enhance the kinetic solubility and dissolution rate of poorly soluble drugs. Nanocrystals are simply obtained by milling large-sized drug powders to sizes < 1 µm. The so obtained nanocrystals possess an increased dissolution rate and kinetic solubility when compared with larger-sized bulk material. The aim of this study was to produce differently sized hesperetin nanocrystals and to investigate the influence of nanocrystal size on the bioefficacy of the natural antioxidant hesperetin in two cell culture models for the prevention and treatment of Alzheimer’s disease. Results showed that the testing of poorly soluble compounds is challenging and requires incredibly careful characterization. Reasons for this are possible changes of the formulations in cell culture media which can occur due to various reasons. If the changes are not considered, results obtained can be misleading and even lead to a false interpretation of the results obtained. Besides, results demonstrate the increase in dissolution rate with decreasing particle size that is especially pronounced with particle sizes < 200 nm. Data also provide clear evidence that smaller nanocrystals with higher kinetic solubility possess higher antioxidant capacity. This results in lower amounts of free radicals in the cell culture models, suggesting that hesperetin nanocrystals, that improve the poor aqueous solubility of hesperetin, are promising for the prevention and treatment of Alzheimer’s disease. Graphical abstract "Image missing"
Pascal-L. Stahr; Rekha Grewal; Gunter P. Eckert; Cornelia M. Keck. Investigating hesperetin nanocrystals with tailor-made sizes for the prevention and treatment of Alzheimer’s disease. Drug Delivery and Translational Research 2021, 11, 659 -674.
AMA StylePascal-L. Stahr, Rekha Grewal, Gunter P. Eckert, Cornelia M. Keck. Investigating hesperetin nanocrystals with tailor-made sizes for the prevention and treatment of Alzheimer’s disease. Drug Delivery and Translational Research. 2021; 11 (2):659-674.
Chicago/Turabian StylePascal-L. Stahr; Rekha Grewal; Gunter P. Eckert; Cornelia M. Keck. 2021. "Investigating hesperetin nanocrystals with tailor-made sizes for the prevention and treatment of Alzheimer’s disease." Drug Delivery and Translational Research 11, no. 2: 659-674.
Many active pharmaceutical ingredients (API) possess poor aqueous solubility and thus lead to poor bioavailability upon oral administration and topical application. Nanocrystals have a well-established, universal formulation approach to overcome poor solubility. Various nanocrystal-based products have entered the market for oral application. However, their use in dermal formulations is relatively novel. Previous studies confirmed that nanocrystals are a superior formulation principle to improve the dermal penetration of poorly soluble API. Other studies showed that nanocrystals can also be used to target the hair follicles where they create a drug depot, enabling long acting drug therapy with only one application. Very recent studies show that also the vehicle in which the nanocrystals are incorporated can have a tremendous influence on the pathway of the API and the nanocrystals. In order to elucidate the influence of the excipient in more detail, a systematic study was conducted to investigate the influence of excipients on the penetration efficacy of the formulated API and the pathway of nanocrystals upon dermal application. Results showed that already small quantities of excipients can strongly affect the passive dermal penetration of curcumin and the hair follicle targeting of curcumin nanocrystals. The addition of 2% ethanol promoted hair follicle targeting of nanocrystals and hampered passive diffusion into the stratum corneum of the API, whereas the addition of glycerol hampered hair follicle targeting and promoted passive diffusion. Propylene glycol was found to promote both pathways. In fact, the study proved that formulating nanocrystals to improve the bioefficacy of poorly soluble API upon dermal application is highly effective. However, this is only true, if the correct excipient is selected for the formulation of the vehicle. The study also showed that excipients can be used to allow for a targeted dermal drug delivery, which enables to control if API should be delivered via passive diffusion and/or as drug reservoir by depositing API in the hair follicles.
Olga Pelikh; Cornelia M. Keck. Hair Follicle Targeting and Dermal Drug Delivery with Curcumin Drug Nanocrystals—Essential Influence of Excipients. Nanomaterials 2020, 10, 2323 .
AMA StyleOlga Pelikh, Cornelia M. Keck. Hair Follicle Targeting and Dermal Drug Delivery with Curcumin Drug Nanocrystals—Essential Influence of Excipients. Nanomaterials. 2020; 10 (11):2323.
Chicago/Turabian StyleOlga Pelikh; Cornelia M. Keck. 2020. "Hair Follicle Targeting and Dermal Drug Delivery with Curcumin Drug Nanocrystals—Essential Influence of Excipients." Nanomaterials 10, no. 11: 2323.
Nanocrystals are a universal formulation approach for improved drug delivery of poorly water-soluble drug substances. Besides oral application, also topical application of the nanocrystals is feasible, because the increased kinetic solubility of the nanocrystals results in an increased concentration gradient, thus fostering passive, dermal penetration. Nanocrystals are also promising for targeting drug substances into the hair follicle. After penetration into the hair follicle, the nanocrystals could form a depot from which the active is released into the hair follicle. Thus, leading to a long-lasting and very efficient dermal drug delivery. The efficacy of nanocrystals to penetrate the hair follicles and the influence of the vehicle in which the nanocrystals are suspended was not yet investigated. Therefore, in this study curcumin nanocrystals with a size of about 300 nm were produced and incorporated into gels with different properties. The efficacy to penetrate the hair follicles, as well as the passive, dermal penetration, was assessed on the ex-vivo pig ear model. Nanocrystals were efficiently taken up by the hair follicles and reached the lower part of the infundibulum. This region is optimal for efficient drug delivery because the barrier of the lower infundibulum is not fully developed and thus more permeable, which results in a less hindered passive diffusion of drug substances. The penetration efficacy of the nanocrystals into the hair follicles was not affected by the different types of vehicles, which represented either oleogels or hydrogels that varied in viscosity as well as in the type and the concentration of the gelling agent. All gels possessed a shear-thinning flow behavior and it is hypothesized that all gels fluidized during the skin massage, whereby leading to similarly low viscosities than the aqueous nanosuspension and thus to similar penetration results. The passive, dermal penetration of curcumin was different for the different gels and the main driving parameter leading to good passive diffusion was caused by good skin hydrating properties of the vehicle. The best passive penetration was achieved from hydrogels that contained a humectant. However, the addition of the humectant reduced the efficacy of the nanocrystals to penetrate the hair follicle. Data so far, therefore, suggest that hair follicle targeting with nanocrystals that are suspended in water or simple, shear-thinning gels is highly effective. However, the addition of other excipients, e.g. humectants, to these vehicles might cause changes in the penetration profiles. More research in this regard is needed to understand these observations in more detail.
Olga Pelikh; Ralph W. Eckert; Shashank Reddy Pinnapireddy; Cornelia M. Keck. Hair follicle targeting with curcumin nanocrystals: Influence of the formulation properties on the penetration efficacy. Journal of Controlled Release 2020, 329, 598 -613.
AMA StyleOlga Pelikh, Ralph W. Eckert, Shashank Reddy Pinnapireddy, Cornelia M. Keck. Hair follicle targeting with curcumin nanocrystals: Influence of the formulation properties on the penetration efficacy. Journal of Controlled Release. 2020; 329 ():598-613.
Chicago/Turabian StyleOlga Pelikh; Ralph W. Eckert; Shashank Reddy Pinnapireddy; Cornelia M. Keck. 2020. "Hair follicle targeting with curcumin nanocrystals: Influence of the formulation properties on the penetration efficacy." Journal of Controlled Release 329, no. : 598-613.
PlantCrystals are obtained by milling plant material to sizes <10 µm. Due to the disruption of the plant cells, active compounds are easily released, rendering the PlantCrystal technology an effective and low-cost process for the production of environmentally friendly plant extracts. The extracts can be used to produce phytomedicines, nutritional supplements or cosmetic products. Previous studies could already demonstrate the use of PlantCrystals to improve the antimicrobial or antifungal activity of different plants. This study investigated whether PlantCrystal technology is suitable to produce plant derived formulations with high antioxidant capacity. The study also aimed to identify the most suitable production methods for this. Methods: Various plant materials and parts of plants, i.e., seeds, leaves and flowers, and different methods were employed for the production. PlantCrystals were characterized regarding size, physical stability and antioxidant capacity (AOC). Results: PlantCrystals with particles <1 µm were produced from the different plant materials. Both production methods, i.e., high-pressure homogenization, bead milling or the combination of both were suitable to obtain PlantCrystals. Nano milling of the plant material greatly affected their AOC and resulted in formulations with distinctly higher AOC when compared to classical extracts. Conclusions: Rendering plant material into small sized particles is highly effective to obtain plant extracts with high biological efficacy.
Abraham M. Abraham; Reem M. Alnemari; Claus Jacob; Cornelia M. Keck. PlantCrystals—Nanosized Plant Material for Improved Bioefficacy of Medical Plants. Materials 2020, 13, 4368 .
AMA StyleAbraham M. Abraham, Reem M. Alnemari, Claus Jacob, Cornelia M. Keck. PlantCrystals—Nanosized Plant Material for Improved Bioefficacy of Medical Plants. Materials. 2020; 13 (19):4368.
Chicago/Turabian StyleAbraham M. Abraham; Reem M. Alnemari; Claus Jacob; Cornelia M. Keck. 2020. "PlantCrystals—Nanosized Plant Material for Improved Bioefficacy of Medical Plants." Materials 13, no. 19: 4368.
Zusammenfassung Die Pflege und Gesunderhaltung der Haut ist nicht nur für ein gutes Aussehen, sondern auch für das allgemeine Wohlbefinden essenziell. Viele Menschen investieren daher für die Hautpflege nicht nur viel Zeit, sondern auch viel Geld. Oft stellt sich jedoch die Frage, welche Produkte aus der Vielfalt an Angeboten nun besonders effektiv und empfehlenswert sind. Der Artikel gibt darüber Auskunft. Er erläutert die Grundlagen und aktuellen Erkenntnisse der Corneobiologie und zeigt, wie eine präzise, effektive und nachhaltige Hautpflege heute aussehen sollte.
Cornelia M. Keck. Corneotherapie – Pflege und Reparatur der Haut: präzise, effektiv und nachhaltig. Journal für Ästhetische Chirurgie 2020, 13, 132 -142.
AMA StyleCornelia M. Keck. Corneotherapie – Pflege und Reparatur der Haut: präzise, effektiv und nachhaltig. Journal für Ästhetische Chirurgie. 2020; 13 (3):132-142.
Chicago/Turabian StyleCornelia M. Keck. 2020. "Corneotherapie – Pflege und Reparatur der Haut: präzise, effektiv und nachhaltig." Journal für Ästhetische Chirurgie 13, no. 3: 132-142.
Newly developed active pharmaceutical ingredients (API) often experience low solubility in aqueous media and thus possess poor oral bioavailability. The SmartFilm®-technology is a novel approach to overcome poor solubility. The technique uses commercial paper in which API can be loaded in amorphous state, thus increasing dissolution rate dc/dt and solubility cs when compared to bulk material. However, the preservation of the amorphous state is a prerequisite for an efficient use of the smartFilm-technology and thus the crystalline state needs to be inspected during storage. Preferably, this should be done non-destructively. Traditional techniques, such as x-ray diffraction (XRD) or differential scanning calorimetry (DSC), do not allow for non-destructive crystallinity investigations, whereas Terahertz (THz) spectroscopy is a non-destructive technique, that is sensitive to the crystalline state of many molecular crystals. Therefore, the potential of THz-spectroscopy for crystallinity state inspection of API in smartFilms and tablets made from smartFilms was investigated in this study. The THz results obtained were compared to results obtained from XRD and DSC measurements. Whereas DSC measurements failed to reliably detect crystalline API in the smartFilms, XRD and THz-spectroscopy showed similar results and revealed that it was possible to prepare smartFilms loaded with >23% (w/w) amorphous API. Results indicate the great potential of THz spectroscopy for the non-destructive determination of the crystalline state of APIs in smartFilms and/or tablets made from paper.
Jan Ornik; Daniel Knoth; Martin Koch; Cornelia M. Keck. Terahertz-spectroscopy for non-destructive determination of crystallinity of L-tartaric acid in smartFilms® and tablets made from paper. International Journal of Pharmaceutics 2020, 581, 119253 .
AMA StyleJan Ornik, Daniel Knoth, Martin Koch, Cornelia M. Keck. Terahertz-spectroscopy for non-destructive determination of crystallinity of L-tartaric acid in smartFilms® and tablets made from paper. International Journal of Pharmaceutics. 2020; 581 ():119253.
Chicago/Turabian StyleJan Ornik; Daniel Knoth; Martin Koch; Cornelia M. Keck. 2020. "Terahertz-spectroscopy for non-destructive determination of crystallinity of L-tartaric acid in smartFilms® and tablets made from paper." International Journal of Pharmaceutics 581, no. : 119253.
Nanocrystals are used as universal approach to improve the bioactivity of poorly soluble active ingredients. They are produced by various techniques, typically yielding aqueous nanosuspensions, which are prone to microbial contamination. Preservation of nanocrystals is possible but might not always be feasible, as preservatives might interfere with other excipients in the formulations or with chemicals used in assays, cell cultures or animal models. Therefore, to enable an easier use of nanocrystals, preservative-free nanosuspensions would be a good alternative. In this study, rutin nanocrystals were frozen and stored for three months at −20 °C. The chemical, physical and microbial stability were monitored, and the results were compared to preserved nanosuspensions. The frozen nanosuspensions remained stable and possessed excellent stability over the whole time of storage, indicating that the freeze–thaw process is suitable for the production of preservative-free nanosuspensions with excellent long-term stability. The freeze–thaw process for nanosuspensions is a simple concept and is suggested as alternative, when preserved nanosuspensions cannot be used.
Pascal L. Stahr; Cornelia M. Keck. Preservation of rutin nanosuspensions without the use of preservatives. Beilstein Journal of Nanotechnology 2019, 10, 1902 -1913.
AMA StylePascal L. Stahr, Cornelia M. Keck. Preservation of rutin nanosuspensions without the use of preservatives. Beilstein Journal of Nanotechnology. 2019; 10 (1):1902-1913.
Chicago/Turabian StylePascal L. Stahr; Cornelia M. Keck. 2019. "Preservation of rutin nanosuspensions without the use of preservatives." Beilstein Journal of Nanotechnology 10, no. 1: 1902-1913.
Nanoparticles are tiny and cannot be seen by the naked eye. They possess different properties than macro-sized material and most of the well-established characterization methods for larger sized materials cannot be applied for nanomaterials. Hence, different techniques need to be used for a meaningful characterization of the nanosized material. This chapter will focus on the most important characterization methods that need to be applied to characterize and develop nanocarrier for cosmetic applications.
Steffen F. Hartmann; Ralph W. Eckert; Daniel Knoth; Cornelia M. Keck. Characterization of Nanoparticles for Cosmetic Applications. Nanocosmetics and Nanomedicines 2019, 181 -198.
AMA StyleSteffen F. Hartmann, Ralph W. Eckert, Daniel Knoth, Cornelia M. Keck. Characterization of Nanoparticles for Cosmetic Applications. Nanocosmetics and Nanomedicines. 2019; ():181-198.
Chicago/Turabian StyleSteffen F. Hartmann; Ralph W. Eckert; Daniel Knoth; Cornelia M. Keck. 2019. "Characterization of Nanoparticles for Cosmetic Applications." Nanocosmetics and Nanomedicines , no. : 181-198.
Dermal application of actives aims at delivering the active to the desired place of action, typically to the deeper layers of the skin. Passive diffusion is the main driving force of absorption into the skin, and a main prerequisite for effective passive diffusion is a sufficient amount of dissolved active within the formulation, because only dissolved molecules can be taken up. Many cosmetic and cosmeceutical actives possess poor solubility and can therefore not be delivered to the skin by classical formulation approaches. One of the modern and most powerful strategies to overcome poor solubility is the use of nanocrystals, which are addressed in this chapter.
Olga Pelikh; Steffen F. Hartmann; Abraham M. Abraham; Cornelia M. Keck. Nanocrystals for Dermal Application. Nanocosmetics and Nanomedicines 2019, 161 -177.
AMA StyleOlga Pelikh, Steffen F. Hartmann, Abraham M. Abraham, Cornelia M. Keck. Nanocrystals for Dermal Application. Nanocosmetics and Nanomedicines. 2019; ():161-177.
Chicago/Turabian StyleOlga Pelikh; Steffen F. Hartmann; Abraham M. Abraham; Cornelia M. Keck. 2019. "Nanocrystals for Dermal Application." Nanocosmetics and Nanomedicines , no. : 161-177.
The investigation of potential health benefits of nano-sized nutriceuticals is recently a major scientific interest. The present study investigated the effect of Selenium and Loranthus micranthus leaves nanoparticles (SeNPs and LMLNPs), on streptozotocin (STZ)-diabetes induced hepato-renal dysfunction in rats. Adult rats were rendered diabetic by a single i.p exposure to 40 mg/kg STZ. Thereafter, rats were treated with 0.1 mg/kg SeNPs or 200 mg/kg LMLNPs, or a combination of both, while 50 mg/kg metformin was used as a standard therapeutic drug. Results indicated that STZ-diabetic rats experienced liver and kidney damage evidenced by a significant elevation in serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and 5' nucleotidase (5'NT) when compared to non-diabetic control rats. Furthermore, a decrease in activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), Glutathione-S-transferase (GST) and glutathione (GSH) levels was observed, whereas myeloperoxidase (MPO) activities and lipid peroxidation (LPO) levels increased significantly in the negative control group compared to the test groups. Immunohistochemical and western blot analyses showed a corresponding elevation in the expression of apoptotic biomarker-caspase 3 and nuclear erythroid 2-related factor 2 (Nrf2) protein in STZ-diabetes group relative to the test groups. SeNPs and/or LMLNPs significantly ameliorated the various alterations imposed by STZ-diabetes relative to the control group. The chemotherapeutic influence in STZ-diabetic rats could be elicited via augmentation of antioxidant defence systems, regulation of Nfr2 expression, decrease in lipid peroxidation and regulation of apoptosis in the studied tissues.
Azubuike P. Ebokaiwe; Omamuyovwi M. Ijomone; Sharoon Griffin; Richard C. Ehiri; Kebe E. Obeten; Joseph O. Nwankwo; Chukwunonso E.C.C. Ejike; Cornelia M. Keck. Nanosized selenium and Loranthus micranthus leaves ameliorate streptozotocin-induced hepato-renal dysfunction in rats via enhancement of antioxidant system, regulation of caspase 3 and Nrf2 protein expression. PharmaNutrition 2019, 9, 100150 .
AMA StyleAzubuike P. Ebokaiwe, Omamuyovwi M. Ijomone, Sharoon Griffin, Richard C. Ehiri, Kebe E. Obeten, Joseph O. Nwankwo, Chukwunonso E.C.C. Ejike, Cornelia M. Keck. Nanosized selenium and Loranthus micranthus leaves ameliorate streptozotocin-induced hepato-renal dysfunction in rats via enhancement of antioxidant system, regulation of caspase 3 and Nrf2 protein expression. PharmaNutrition. 2019; 9 ():100150.
Chicago/Turabian StyleAzubuike P. Ebokaiwe; Omamuyovwi M. Ijomone; Sharoon Griffin; Richard C. Ehiri; Kebe E. Obeten; Joseph O. Nwankwo; Chukwunonso E.C.C. Ejike; Cornelia M. Keck. 2019. "Nanosized selenium and Loranthus micranthus leaves ameliorate streptozotocin-induced hepato-renal dysfunction in rats via enhancement of antioxidant system, regulation of caspase 3 and Nrf2 protein expression." PharmaNutrition 9, no. : 100150.
At present, there is an increasing demand to improve the sustainability of surface-active compounds in dermal formulations. Biosurfactants, which are derived from living cells, are considered to be more environmentally friendly than synthetic surfactants. Thus, the use of biosurfactants is a promising strategy for the formulation of more environmentally friendly and sustainable dermal products. In this work, a biosurfactant extract (BS) obtained from corn wet-milling industry was studied for its potential use in dermal formulations. The corn derived BS possesses good surface-active properties and was found to be a suitable co-stabilizer for nanoemulsions and nanocrystals for dermal application. It also possesses antioxidative and skin protective properties and was also able to increase the dermal penetration efficacy for lipophilic actives. In dermal formulations the BS can therefore be used as co-stabilizer with antioxidative and penetration enhancing properties at the same time.
D. Knoth; M. Rincón-Fontán; P.-L. Stahr; O. Pelikh; R.-W. Eckert; H. Dietrich; J.M. Cruz; A.B. Moldes; C.M. Keck. Evaluation of a biosurfactant extract obtained from corn for dermal application. International Journal of Pharmaceutics 2019, 564, 225 -236.
AMA StyleD. Knoth, M. Rincón-Fontán, P.-L. Stahr, O. Pelikh, R.-W. Eckert, H. Dietrich, J.M. Cruz, A.B. Moldes, C.M. Keck. Evaluation of a biosurfactant extract obtained from corn for dermal application. International Journal of Pharmaceutics. 2019; 564 ():225-236.
Chicago/Turabian StyleD. Knoth; M. Rincón-Fontán; P.-L. Stahr; O. Pelikh; R.-W. Eckert; H. Dietrich; J.M. Cruz; A.B. Moldes; C.M. Keck. 2019. "Evaluation of a biosurfactant extract obtained from corn for dermal application." International Journal of Pharmaceutics 564, no. : 225-236.