Christel Müller-Goymann - Academia.edu (original) (raw)

Papers by Christel Müller-Goymann

Rivista Italiana Delle Sostanze Grasse, 2005

The aim of this study Was to Examine the lyotropic potential of an alkylpolyglucoside mixed Emuls... more The aim of this study Was to Examine the lyotropic potential of an alkylpolyglucoside mixed Emulsifier (Cetearyl Glucoside & Cetearyl alcohol), Which Belongs to the new generation of natural (sugar) surfactants, and to elaborate the stabilization mechanism and relation Between the colloid microstructure and water distribution Within the systems. Polarization and ordinary light as well as transmission electron microscopy, wide angle X-ray diffraction, thermal analysis and rheological measurement, as well as in vivo hydration potential Were employed for testing the systems Characterization. A comparison of results Obtained from Isothermal thermogravimetry and in vivo short-term application study served to Recognize Within water distribution systems and the dynamic of water evaporation, ie to consider in the Possibility of Formulation and Prolonged water emulsion with controlled release. It Was Suggested That Cetearyl glucoside & Cetearyl alcohol stabilizes the o / w creams by synergis...

Planta Medica, 2018

The discovery of immunostimulating complex formation by the saponin Quil A from the plant Quillaj... more The discovery of immunostimulating complex formation by the saponin Quil A from the plant Quillaja saponaria with cholesterol and a phospholipid opened up new avenues for the development of drug delivery systems for vaccine application with additional adjuvant properties. In this study, β-escin, a monodesmosidic triterpene saponin from horse chestnut, was investigated in terms of its interaction with liposomal components (cholesterol, dipalmitoylphosphatidylcholine) by Langmuir film balance studies and with regard to particle formation visualized by transmission electron microscopy. A strong interaction of β-escin with cholesterol was observed by Langmuir isotherms due to the intercalation of the saponin into the monolayer, whereas no interaction occurred with dipalmitoylphosphatidylcholine. Transmission electron microscopy studies also confirmed the strong interaction of β-escin with cholesterol. In aqueous pseudo-ternary systems (β-escin, dipalmitoylphosphatidylcholine, cholestero...

Planta Medica, 2018

The hyperforin content of Hypericum perforatum herb was repeatedly reported to be responsible for... more The hyperforin content of Hypericum perforatum herb was repeatedly reported to be responsible for a multitude of pharmacological activities. Our recent report about the hyperforin accumulation in in vitro root cultures of H. perforatum provides an alternative perspective to achieve constant product quality and to serve the rapidly growing market. In this study, the antiproliferative effect of a petroleum ether extract from the in vitro root cultures was investigated. When normalized to 1 µM hyperforin content, the extract reduced the viability of human keratinocytes (HaCaT) and human dermal fibroblast monolayers to 33 and 36%, respectively, after 72 h of incubation. A cytotoxicity assay and live-dead cell staining confirmed that the extract lacked a cytotoxic effect and that the reduction in cell viability was mainly due to the antiproliferative activity. Application of the 1 µM hyperforin-normalized extract to a 3D artificial skin construct significantly reduced the proliferation o...

Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics, 2017

The aim of the present study was to develop acyclovir (ACV) ocular drug delivery systems of bovin... more The aim of the present study was to develop acyclovir (ACV) ocular drug delivery systems of bovine serum albumin (BSA) nanoparticles as well as to assess their in vitro transcorneal permeation across human corneal epithelial (HCE-T) cell multilayers. The ACV-loaded BSA nanoparticles were prepared by desolvation method along with physicochemical characterization, cytotoxicity, as well as in vitro transcorneal permeation studies across HCE-T cell multilayers. The nanoparticles appeared to be spherical in shape and nearly uniform in size of about 200 nm. The size of nanoparticles became smaller with decreasing BSA concentration, while the ratios of water to ethanol seemed not to affect the size. Increasing the amount of ethanol in desolvation process led to significant reduction of drug entrapment of nanoparticles with smaller size and more uniformity. The ACV-loaded BSA nanoparticles prepared were shown to have no cytotoxic effect on HCE-T cells used in permeation studies. The in vitr...

International Journal of Pharmaceutics, 2006

Carnauba wax is partially composed of cinnamates. The rational combination of cinnamates and tita... more Carnauba wax is partially composed of cinnamates. The rational combination of cinnamates and titanium dioxide has shown a synergistic effect to improve the sun protection factor (SPF) of cosmetic preparations. However, the mechanism of this interaction has not been fully understood. In this study, an ethanolic extract of the carnauba wax and an ethanolic solution of a typical cinnamate derivative, ethylcinnamate, were prepared and their UV absorption and SPF either alone or in the presence of titanium dioxide were compared. The titanium dioxide crystals and the cinnamates solutions were also distributed into a matrix composed of saturated fatty acids to emulate the structure of the crystallized carnauba wax. SPF, differential scanning calorimetry (DSC) and X-ray studies of these matrices were performed. Additionally, carnauba wax nanosuspensions containing titanium dioxide either in the lipid phase or in the aqueous phase were prepared to evaluate their SPFs and their physical structure. Strong UV absorption was observed in diluted suspensions of titanium dioxide after the addition of cinnamates. The saturated fatty acid matrices probably favored the adsorption of the cinnamates at the surface of titanium dioxide crystals, which was reflected by an increase in the SPF. No modification of the crystal structure of the fatty acid matrices was observed after the addition of cinnamates or titanium dioxide. The distribution of the titanium dioxide inside the lipid phase of the nanosuspensions was more effective to reach higher SPFs than that at the aqueous phase. The close contact between the carnauba wax and the titanium dioxide crystals after the high-pressure homogenization process was confirmed by transmission electron microscopy (TEM).

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, Jan 2, 2017

Hyperforin is a major active constituent of Hypericum perforatum (St. John's wort). It has am... more Hyperforin is a major active constituent of Hypericum perforatum (St. John's wort). It has amazing pharmacological activities, such as antidepressant properties, but it is labile and difficult to synthesize. Its sensitivity and lipophilicity are challenges for processing and formulation. Its chemical complexity provokes approaches of biotechnological production and modification. Dedifferentiated H. perforatum cell cultures lack appropriate storage sites and hence appreciable hyperforin levels. Shoot cultures are capable of forming hyperforin but less suitable for biomass up-scaling in bioreactors. Roots commonly lack hyperforin but a recently established adventitious root line has been demonstrated to produce hyperforin and derivatives at promising levels. The roots also contained lupulones, the typical constituents of hop (Humulus lupulus). Although shear-sensitive, these root cultures provide a potential production platform for both individual compounds and extracts with novel...

BMC veterinary research, 2016

Due to antibiotic treatment of humans and animals, the prevalence of bacterial resistances increa... more Due to antibiotic treatment of humans and animals, the prevalence of bacterial resistances increases worldwide. Especially in livestock farming, large quantities of faeces contaminated with antibiotics pose a risk of the carryover of the active ingredient to the environment. Accordingly, the aim of the present study was the evaluation of the benefit of different oral dosage forms (powder, pellets, granula) in pigs concerning the environmental pollution of sulfadiazine. Two subtherapeutic dosages were evaluated in powder mixtures to gain information about their potential to pollute the pig barn. Furthermore, a new group of pigs was kept in the stable after powder feeding of another pig group to determine the possible absorption of environmentally distributed antibiotics. Pigs were orally treated with three dosage forms. Simultaneously, sedimentation and airborne dust were collected and plasma and urine levels were determined. All formulations result in comparable plasma and urine lev...

International Journal of Pharmaceutics, 2005

Lipid nanoparticles (LNP) based on triglycerides containing high amounts of the amphiphilic lipid... more Lipid nanoparticles (LNP) based on triglycerides containing high amounts of the amphiphilic lipid lecithin have been proposed as a promising alternative drug delivery system with regard to drug loading capacity. Aim of the present study is to evaluate the influence of lecithin within the lipid matrix (LM) on the crystallization behavior by thermoanalysis and wide angle X-ray diffraction (WAXD). The crystallinity of LM and LNP is mainly determined by the triglyceride content. However, lecithin influences the crystallization behavior significantly. WAXD shows an accelerated polymorphic transition of the LM to the ␤-modification upon storage with increasing lecithin content. Both, the melting point and the crystallization temperature are not affected by the lecithin concentration and are comparable to recrystallized triglyceride bulk. However, the crystallinity indices (CI) of LM show a general decrease by 10% suggesting an incomplete crystallization. For the formation of LNP at least 10% lecithin is necessary and all systems are present in the stable ␤-modification. In comparison to the undispersed LM, the crystallization temperature of LNP is significantly decreased by about 20 • C whereas the melting point is reduced by about 5 • C only. Melting enthalpy is comparable to the untreated triglyceride bulk and elevated in comparison to the undispersed LM. Isothermal heat-conduction microcalorimetry (IMC) enables the determination of crystallization kinetics after fitting of the heat flow volume according to the Avrami equation.

International journal of pharmaceutics, Jan 31, 2006

An emerging class of natural surfactants, named alkylpolyglucosides, which can form both, the the... more An emerging class of natural surfactants, named alkylpolyglucosides, which can form both, the thermotropic and the lyotropic liquid crystalline phases, were focused. The aim of the study was to integrate some physicochemical properties (characterised through the polarization and transmission electron microscopy, wide-angle X-ray diffraction, thermal analysis and rheology) of the three formulations based on cetearyl glucoside and cetearyl alcohol, with the in vitro (the artificial skin constructs) and in vivo bioavailability of hydrocortisone (HC), in comparison with a standard pharmacopoeial vehicle. The parameters measured in vivo were erythema index (an instrumental human skin blanching assay), transepidermal water loss (TEWL) and stratum corneum hydration. A complex colloidal structure of lamellar liquid crystalline and lamellar gel crystalline type was deduced for sugar surfactant-based vehicles. In dependence on surfactant/water/oil ratio, several thermodynamically variable fra...

A68. AN ENDOCRINE STUDY OF THE LUNG: GLUCOCORTICOIDS, SEX, AND OTHER HORMONES, 2011

Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany, Technische Univ... more Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany, Technische Universität Braunschweig, 1 ... Braunschweig, Germany, Fraunhofer ITEM, Hannover, Germany 3 ... : The incidence of pulmonary diseases is increasing and leads to a boosted need for ...

Pharmaceutical Research, 1997

Purpose. Reverse micellar solutions of diclofenac sodium were encapsulated in soft gelatine capsu... more Purpose. Reverse micellar solutions of diclofenac sodium were encapsulated in soft gelatine capsules. On contact with aqueous media they exhibited an application induced transformation (AIT) into a semisolid system of liquid crystals (SSLC) which slows down drug release. The aim of the present paper was to study in vitro and in vivo drug release from these systems after rectal application.

Skin Pharmacology and Physiology, 2003

The influence of isopropyl myristate (IPM), isopropyl alcohol (IPA) and a combination of both was... more The influence of isopropyl myristate (IPM), isopropyl alcohol (IPA) and a combination of both was studied in view of hydrocortisone (HC) permeation across the human stratum corneum (SC). IPM, IPA and their combination were incorporated into water-containing hydrophilic ointment (WHS), and the resulting effects on HC permeation and on HC accumulation in human SC were investigated as well as the influence of these substances on the microstructure of the SC. Differential scanning calorimetry as well as wide- and small-angle X-ray diffraction show that IPM incorporation into SC results in densely packed bilayer lipids and a loss of order of the corneocyte-bonded lipids. Both effects result in a decreased diffusion coefficient of HC in SC and thus in a decreased permeation rate compared to that of HC from WHS. On the other hand, IPA fluidizes and disrupts the bilayer structure of the intercellular lipids. These effects, concomitant with an increased amount of dissolved HC within the oint...

Pharmaceutical Research - PHARMACEUT RES, 1998

Purpose. Loading a liposomal dispersion with drug may cause a phase transformation into a micella... more Purpose. Loading a liposomal dispersion with drug may cause a phase transformation into a micellar solution. The present contribution presents a detailed physicochemical characterization and an overall model which describes transformation due to the properties of any drug.

Der Ophthalmologe, 2005

Zusammenfassung Organotypische Hornhautäquivalente werden als In-vitro-Modelle für Arzneistoffabs... more Zusammenfassung Organotypische Hornhautäquivalente werden als In-vitro-Modelle für Arzneistoffabsorptionsuntersuchungen verwendet. Viele ophthalmologische Wirkstoffe werden zur Erhöhung der Bioverfügbarkeit als Ester-Prodrugs eingesetzt. Es wurde die Esteraseaktivität von drei kornealen humanen Zelllinien (Epithel-, Stroma- und Endothelzellen) sowie von exzidierter porciner Kornea, humaner Spenderkornea und einem humanen Kornea-Konstrukt (HCC) untersucht und verglichen.

Inhalation Toxicology, 2009

The aim of this study was to investigate the potential cytotoxicity of solid lipid nanoparticles ... more The aim of this study was to investigate the potential cytotoxicity of solid lipid nanoparticles (SLN) for human lung as a suitable drug delivery system (DDS). Therefore we used a human alveolar epithelial cell line (A549) and murine precision-cut lung slices (PCLS) to estimate the tolerable doses of these particles for lung cells. A549 cells (in vitro) and precision-cut lung slices (ex vivo) were incubated with SLN20 (20% phospholipids in the lipid matrix of the particles) and SLN50 (50% phospholipids in the lipid matrix of the particles) in increasing concentrations. The cytotoxic effects of SLN were evaluated in vitro by lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Vitality of lung slices was controlled by staining with calcein AM/ethidium homodimer 1 using confocal laser scanning microscopy and followed by quantitative image analysis with IMARIS software. A549 cell line revealed a middle effective concentration (EC(50)) for MTT assay for SLN20 of 4080 microg/ml and for SLN50 of 1520 microg/ml. The cytotoxicity in terms of LDH release showed comparable EC(50) values of 3431 microg/ml and 1253 microg/ml for SLN20 and SLN50, respectively. However, in PCLS we determined only SLN50 cytotoxic values with a concentration of 1500 microg/ml. The lung slices seem to be a more sensitive test system. SLN20 showed lower toxic values in all test systems. Therefore we conclude that SLN20 could be used as a suitable DDS for the lung, from a toxicological point of view.

European Journal of Pharmaceutics and Biopharmaceutics, 2005

Transcorneal in vitro permeation studies of ophthalmic drugs are normally performed with either e... more Transcorneal in vitro permeation studies of ophthalmic drugs are normally performed with either excised animal corneas or latterly corneal cell culture models. A good correlation between these models and excised animal corneas regarding permeation behaviour of drugs has already been shown. However, comparisons between corneal in vitro models containing human cells and excised human corneas do not exist yet. Therefore in the present study the transcorneal permeation of six different model drugs (pilocarpine hydrochloride, befunolol hydrochloride, hydrocortisone, diclofenac sodium, clindamycin hydrochloride and timolol maleate) across our previously described three-dimensional organotypic human cornea construct (HCC) was tested using Franz diffusion cells and compared with permeation data obtained from human donor corneas. The HCC showed a similar permeation behaviour compared with human donor cornea for all substances. The permeabilities (permeation coefficients P) of the human cornea equivalent versus the human donor cornea were the same in the case of diclofenac, clindamycin, timolol, but marginally decreased for hydrocortisone and slightly increased for pilocarpine and befunolol. These small differences of permeation coefficients were expressed as factors and only varied from 0.8 to 1.4. The results indicate that the HCC may be an alternative for in vitro permeation studies and appropriate for predicting drug absorption into the human eye.

European Journal of Pharmaceutics and Biopharmaceutics, 2003

Lipid nanoparticles (LNP) can be prepared by rapidly injecting a solution of solid lipids in wate... more Lipid nanoparticles (LNP) can be prepared by rapidly injecting a solution of solid lipids in water-miscible solvents or a water-miscible solvent mixture into water. The aim of the present study was to evaluate the potential of this method for the preparation of LNP and the physicochemical characterization of the particles produced by this method. The results show that solvent injection is a potent and versatile approach for LNP preparation. Acetone, ethanol, isopropanol and methanol are suitable solvents in contrast to ethylacetate with which no LNP could be prepared. The obtained particle sizes (z-average) were between 80 and 300 nm depending on the preparation conditions. Up to 96.5% of the employed lipid was directly transformed into LNP. The LNP formation process seems to be diffusion controlled. Physicochemical characterization of the particles by differential scanning calorimetry (DSC), transmission electron microscopy and X-ray diffraction analysis reveals a distinct decrease in crystallinity of the colloidal lipid in comparison to the bulk lipid. Furthermore, DSC analysis of LNP hints at a delayed recrystallization of the colloidal lipid and the presence of two modifications. Therefore, a certain physical instability of the LNP has to be considered.

European Journal of Pharmaceutics and Biopharmaceutics, 2005

Solid lipid nanoparticles (SLN), an alternative colloidal drug delivery system to polymer nanopar... more Solid lipid nanoparticles (SLN), an alternative colloidal drug delivery system to polymer nanoparticles, emulsions and liposomes, are generally produced by high pressure melt-emulsification. However, the harsh production process is not applicable for formulations containing shear and temperature sensitive compounds. For that reason, subsequent adsorptive SLN loading might be a promising alternative. The aim of the present study was the development and characterisation of surface-modified SLN for adsorptive protein loading by variation of both the lipid matrix and the emulsifier concentration in the continuous phase. Variations in SLN composition resulted in particle sizes between 674 and 61 nm corresponding to specific surfaces of 4.5 m 2 /g and 48.9 m 2 /g and zeta potentials between K23.4 mV and K0.9 mV. In dependence of SLN surface properties, albumin payload ranged from 2.5 to 15%. Thermoanalysis, X-ray diffraction and electron microscopy revealed anisometrical and crystalline particles. In vitro cytotoxicity was low in terms of both haemolysis, which was between 1 and 2%, and neutral red test (NRT) showing a half lethal dose between 1.1 and 4.6%.

European Journal of Pharmaceutics and Biopharmaceutics, 2010

Inhalation is a non-invasive approach for both local and systemic drug delivery. This study aimed... more Inhalation is a non-invasive approach for both local and systemic drug delivery. This study aimed to define the therapeutic window for solid lipid nanoparticles (SLNs) as a drug delivery system by inhalation from a toxicological point of view. To estimate the toxic dose of SLNs in vitro, A549 cells and murine precision-cut lung slices (PCLS) were exposed to increasing concentrations of SLNs. The cytotoxic effect of SLNs on A549 cells was evaluated by MTT and NRU assays. Viability of lung tissue was determined with WST assay and by life/dead staining using calcein AM/EthD-1 for confocal microscopy (CLSM) followed by quantitative analysis with IMARIS. Inflammation was assessed by measuring chemokine KC and TNF-a levels. The in vivo effects were determined in a 16-day repeated-dose inhalation toxicity study using female BALB/c mice, which were daily exposed to different concentrations of SLN30 aerosols (1-200 lg deposit dose). Local inflammatory effects in the respiratory tract were evaluated by determination of total protein content, LDH, chemokine KC, IL-6, and differential cell counts, performed on days 4, 8, 12, and 16 in bronchoalveolar lavage fluid. Additionally, a histopathological evaluation of toxicologically relevant organs was accomplished. The in vitro and ex vivo dose finding experiments showed toxic effects beginning at concentrations of about 500 lg/ml. Therefore, we used 1-200 lg deposit doses/animal for the in vivo experiments. Even after 16 days of challenge with a 200-lg deposit dose, SLNs induced no significant signs of inflammation. We observed no consistent increase in LDH release, protein levels, or other signs of inflammation such as chemokine KC, IL-6, or neutrophilia. In contrast, the particle control (carbon black) caused inflammatory and cytotoxic effects at corresponding concentrations. These results confirm that repeated inhalation exposure to SLN30 at concentrations lower than a 200lg deposit dose is safe in a murine inhalation model.

European Journal of Pharmaceutics and Biopharmaceutics, 2002

Dilution of semisolid preparations, in order to tailor the formulations to the needs of the patie... more Dilution of semisolid preparations, in order to tailor the formulations to the needs of the patients, was thought to be associated with a number of dangers, one of which is the unpredictable alteration of activity. In the present study the influence of dilution on hydrocortisone permeation through excised human stratum corneum was investigated. The permeation profiles of hydrocortisone from various cream bases (diluted and undiluted) were found to be very similar with no significant differences. This result was in accordance with the lack of interaction between the tested bases and the structure of stratum corneum as shown by differential scanning calorimetry experiments. Thus, the permeability of stratum corneum, which was not affected by the cream bases, is the rate limiting step for drug permeation. However, it could be shown that dilution of Soventol cream (placebo with 1% hydrocortisone) which is known to contain isopropyl myristate as permeation enhancer reduces drug permeation. The reduced hydrocortisone permeation is believed to be due to reduced enhancer concentration.

Rivista Italiana Delle Sostanze Grasse, 2005

The aim of this study Was to Examine the lyotropic potential of an alkylpolyglucoside mixed Emuls... more The aim of this study Was to Examine the lyotropic potential of an alkylpolyglucoside mixed Emulsifier (Cetearyl Glucoside & Cetearyl alcohol), Which Belongs to the new generation of natural (sugar) surfactants, and to elaborate the stabilization mechanism and relation Between the colloid microstructure and water distribution Within the systems. Polarization and ordinary light as well as transmission electron microscopy, wide angle X-ray diffraction, thermal analysis and rheological measurement, as well as in vivo hydration potential Were employed for testing the systems Characterization. A comparison of results Obtained from Isothermal thermogravimetry and in vivo short-term application study served to Recognize Within water distribution systems and the dynamic of water evaporation, ie to consider in the Possibility of Formulation and Prolonged water emulsion with controlled release. It Was Suggested That Cetearyl glucoside & Cetearyl alcohol stabilizes the o / w creams by synergis...

Planta Medica, 2018

The discovery of immunostimulating complex formation by the saponin Quil A from the plant Quillaj... more The discovery of immunostimulating complex formation by the saponin Quil A from the plant Quillaja saponaria with cholesterol and a phospholipid opened up new avenues for the development of drug delivery systems for vaccine application with additional adjuvant properties. In this study, β-escin, a monodesmosidic triterpene saponin from horse chestnut, was investigated in terms of its interaction with liposomal components (cholesterol, dipalmitoylphosphatidylcholine) by Langmuir film balance studies and with regard to particle formation visualized by transmission electron microscopy. A strong interaction of β-escin with cholesterol was observed by Langmuir isotherms due to the intercalation of the saponin into the monolayer, whereas no interaction occurred with dipalmitoylphosphatidylcholine. Transmission electron microscopy studies also confirmed the strong interaction of β-escin with cholesterol. In aqueous pseudo-ternary systems (β-escin, dipalmitoylphosphatidylcholine, cholestero...

Planta Medica, 2018

The hyperforin content of Hypericum perforatum herb was repeatedly reported to be responsible for... more The hyperforin content of Hypericum perforatum herb was repeatedly reported to be responsible for a multitude of pharmacological activities. Our recent report about the hyperforin accumulation in in vitro root cultures of H. perforatum provides an alternative perspective to achieve constant product quality and to serve the rapidly growing market. In this study, the antiproliferative effect of a petroleum ether extract from the in vitro root cultures was investigated. When normalized to 1 µM hyperforin content, the extract reduced the viability of human keratinocytes (HaCaT) and human dermal fibroblast monolayers to 33 and 36%, respectively, after 72 h of incubation. A cytotoxicity assay and live-dead cell staining confirmed that the extract lacked a cytotoxic effect and that the reduction in cell viability was mainly due to the antiproliferative activity. Application of the 1 µM hyperforin-normalized extract to a 3D artificial skin construct significantly reduced the proliferation o...

Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics, 2017

The aim of the present study was to develop acyclovir (ACV) ocular drug delivery systems of bovin... more The aim of the present study was to develop acyclovir (ACV) ocular drug delivery systems of bovine serum albumin (BSA) nanoparticles as well as to assess their in vitro transcorneal permeation across human corneal epithelial (HCE-T) cell multilayers. The ACV-loaded BSA nanoparticles were prepared by desolvation method along with physicochemical characterization, cytotoxicity, as well as in vitro transcorneal permeation studies across HCE-T cell multilayers. The nanoparticles appeared to be spherical in shape and nearly uniform in size of about 200 nm. The size of nanoparticles became smaller with decreasing BSA concentration, while the ratios of water to ethanol seemed not to affect the size. Increasing the amount of ethanol in desolvation process led to significant reduction of drug entrapment of nanoparticles with smaller size and more uniformity. The ACV-loaded BSA nanoparticles prepared were shown to have no cytotoxic effect on HCE-T cells used in permeation studies. The in vitr...

International Journal of Pharmaceutics, 2006

Carnauba wax is partially composed of cinnamates. The rational combination of cinnamates and tita... more Carnauba wax is partially composed of cinnamates. The rational combination of cinnamates and titanium dioxide has shown a synergistic effect to improve the sun protection factor (SPF) of cosmetic preparations. However, the mechanism of this interaction has not been fully understood. In this study, an ethanolic extract of the carnauba wax and an ethanolic solution of a typical cinnamate derivative, ethylcinnamate, were prepared and their UV absorption and SPF either alone or in the presence of titanium dioxide were compared. The titanium dioxide crystals and the cinnamates solutions were also distributed into a matrix composed of saturated fatty acids to emulate the structure of the crystallized carnauba wax. SPF, differential scanning calorimetry (DSC) and X-ray studies of these matrices were performed. Additionally, carnauba wax nanosuspensions containing titanium dioxide either in the lipid phase or in the aqueous phase were prepared to evaluate their SPFs and their physical structure. Strong UV absorption was observed in diluted suspensions of titanium dioxide after the addition of cinnamates. The saturated fatty acid matrices probably favored the adsorption of the cinnamates at the surface of titanium dioxide crystals, which was reflected by an increase in the SPF. No modification of the crystal structure of the fatty acid matrices was observed after the addition of cinnamates or titanium dioxide. The distribution of the titanium dioxide inside the lipid phase of the nanosuspensions was more effective to reach higher SPFs than that at the aqueous phase. The close contact between the carnauba wax and the titanium dioxide crystals after the high-pressure homogenization process was confirmed by transmission electron microscopy (TEM).

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, Jan 2, 2017

Hyperforin is a major active constituent of Hypericum perforatum (St. John's wort). It has am... more Hyperforin is a major active constituent of Hypericum perforatum (St. John's wort). It has amazing pharmacological activities, such as antidepressant properties, but it is labile and difficult to synthesize. Its sensitivity and lipophilicity are challenges for processing and formulation. Its chemical complexity provokes approaches of biotechnological production and modification. Dedifferentiated H. perforatum cell cultures lack appropriate storage sites and hence appreciable hyperforin levels. Shoot cultures are capable of forming hyperforin but less suitable for biomass up-scaling in bioreactors. Roots commonly lack hyperforin but a recently established adventitious root line has been demonstrated to produce hyperforin and derivatives at promising levels. The roots also contained lupulones, the typical constituents of hop (Humulus lupulus). Although shear-sensitive, these root cultures provide a potential production platform for both individual compounds and extracts with novel...

BMC veterinary research, 2016

Due to antibiotic treatment of humans and animals, the prevalence of bacterial resistances increa... more Due to antibiotic treatment of humans and animals, the prevalence of bacterial resistances increases worldwide. Especially in livestock farming, large quantities of faeces contaminated with antibiotics pose a risk of the carryover of the active ingredient to the environment. Accordingly, the aim of the present study was the evaluation of the benefit of different oral dosage forms (powder, pellets, granula) in pigs concerning the environmental pollution of sulfadiazine. Two subtherapeutic dosages were evaluated in powder mixtures to gain information about their potential to pollute the pig barn. Furthermore, a new group of pigs was kept in the stable after powder feeding of another pig group to determine the possible absorption of environmentally distributed antibiotics. Pigs were orally treated with three dosage forms. Simultaneously, sedimentation and airborne dust were collected and plasma and urine levels were determined. All formulations result in comparable plasma and urine lev...

International Journal of Pharmaceutics, 2005

Lipid nanoparticles (LNP) based on triglycerides containing high amounts of the amphiphilic lipid... more Lipid nanoparticles (LNP) based on triglycerides containing high amounts of the amphiphilic lipid lecithin have been proposed as a promising alternative drug delivery system with regard to drug loading capacity. Aim of the present study is to evaluate the influence of lecithin within the lipid matrix (LM) on the crystallization behavior by thermoanalysis and wide angle X-ray diffraction (WAXD). The crystallinity of LM and LNP is mainly determined by the triglyceride content. However, lecithin influences the crystallization behavior significantly. WAXD shows an accelerated polymorphic transition of the LM to the ␤-modification upon storage with increasing lecithin content. Both, the melting point and the crystallization temperature are not affected by the lecithin concentration and are comparable to recrystallized triglyceride bulk. However, the crystallinity indices (CI) of LM show a general decrease by 10% suggesting an incomplete crystallization. For the formation of LNP at least 10% lecithin is necessary and all systems are present in the stable ␤-modification. In comparison to the undispersed LM, the crystallization temperature of LNP is significantly decreased by about 20 • C whereas the melting point is reduced by about 5 • C only. Melting enthalpy is comparable to the untreated triglyceride bulk and elevated in comparison to the undispersed LM. Isothermal heat-conduction microcalorimetry (IMC) enables the determination of crystallization kinetics after fitting of the heat flow volume according to the Avrami equation.

International journal of pharmaceutics, Jan 31, 2006

An emerging class of natural surfactants, named alkylpolyglucosides, which can form both, the the... more An emerging class of natural surfactants, named alkylpolyglucosides, which can form both, the thermotropic and the lyotropic liquid crystalline phases, were focused. The aim of the study was to integrate some physicochemical properties (characterised through the polarization and transmission electron microscopy, wide-angle X-ray diffraction, thermal analysis and rheology) of the three formulations based on cetearyl glucoside and cetearyl alcohol, with the in vitro (the artificial skin constructs) and in vivo bioavailability of hydrocortisone (HC), in comparison with a standard pharmacopoeial vehicle. The parameters measured in vivo were erythema index (an instrumental human skin blanching assay), transepidermal water loss (TEWL) and stratum corneum hydration. A complex colloidal structure of lamellar liquid crystalline and lamellar gel crystalline type was deduced for sugar surfactant-based vehicles. In dependence on surfactant/water/oil ratio, several thermodynamically variable fra...

A68. AN ENDOCRINE STUDY OF THE LUNG: GLUCOCORTICOIDS, SEX, AND OTHER HORMONES, 2011

Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany, Technische Univ... more Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany, Technische Universität Braunschweig, 1 ... Braunschweig, Germany, Fraunhofer ITEM, Hannover, Germany 3 ... : The incidence of pulmonary diseases is increasing and leads to a boosted need for ...

Pharmaceutical Research, 1997

Purpose. Reverse micellar solutions of diclofenac sodium were encapsulated in soft gelatine capsu... more Purpose. Reverse micellar solutions of diclofenac sodium were encapsulated in soft gelatine capsules. On contact with aqueous media they exhibited an application induced transformation (AIT) into a semisolid system of liquid crystals (SSLC) which slows down drug release. The aim of the present paper was to study in vitro and in vivo drug release from these systems after rectal application.

Skin Pharmacology and Physiology, 2003

The influence of isopropyl myristate (IPM), isopropyl alcohol (IPA) and a combination of both was... more The influence of isopropyl myristate (IPM), isopropyl alcohol (IPA) and a combination of both was studied in view of hydrocortisone (HC) permeation across the human stratum corneum (SC). IPM, IPA and their combination were incorporated into water-containing hydrophilic ointment (WHS), and the resulting effects on HC permeation and on HC accumulation in human SC were investigated as well as the influence of these substances on the microstructure of the SC. Differential scanning calorimetry as well as wide- and small-angle X-ray diffraction show that IPM incorporation into SC results in densely packed bilayer lipids and a loss of order of the corneocyte-bonded lipids. Both effects result in a decreased diffusion coefficient of HC in SC and thus in a decreased permeation rate compared to that of HC from WHS. On the other hand, IPA fluidizes and disrupts the bilayer structure of the intercellular lipids. These effects, concomitant with an increased amount of dissolved HC within the oint...

Pharmaceutical Research - PHARMACEUT RES, 1998

Purpose. Loading a liposomal dispersion with drug may cause a phase transformation into a micella... more Purpose. Loading a liposomal dispersion with drug may cause a phase transformation into a micellar solution. The present contribution presents a detailed physicochemical characterization and an overall model which describes transformation due to the properties of any drug.

Der Ophthalmologe, 2005

Zusammenfassung Organotypische Hornhautäquivalente werden als In-vitro-Modelle für Arzneistoffabs... more Zusammenfassung Organotypische Hornhautäquivalente werden als In-vitro-Modelle für Arzneistoffabsorptionsuntersuchungen verwendet. Viele ophthalmologische Wirkstoffe werden zur Erhöhung der Bioverfügbarkeit als Ester-Prodrugs eingesetzt. Es wurde die Esteraseaktivität von drei kornealen humanen Zelllinien (Epithel-, Stroma- und Endothelzellen) sowie von exzidierter porciner Kornea, humaner Spenderkornea und einem humanen Kornea-Konstrukt (HCC) untersucht und verglichen.

Inhalation Toxicology, 2009

The aim of this study was to investigate the potential cytotoxicity of solid lipid nanoparticles ... more The aim of this study was to investigate the potential cytotoxicity of solid lipid nanoparticles (SLN) for human lung as a suitable drug delivery system (DDS). Therefore we used a human alveolar epithelial cell line (A549) and murine precision-cut lung slices (PCLS) to estimate the tolerable doses of these particles for lung cells. A549 cells (in vitro) and precision-cut lung slices (ex vivo) were incubated with SLN20 (20% phospholipids in the lipid matrix of the particles) and SLN50 (50% phospholipids in the lipid matrix of the particles) in increasing concentrations. The cytotoxic effects of SLN were evaluated in vitro by lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Vitality of lung slices was controlled by staining with calcein AM/ethidium homodimer 1 using confocal laser scanning microscopy and followed by quantitative image analysis with IMARIS software. A549 cell line revealed a middle effective concentration (EC(50)) for MTT assay for SLN20 of 4080 microg/ml and for SLN50 of 1520 microg/ml. The cytotoxicity in terms of LDH release showed comparable EC(50) values of 3431 microg/ml and 1253 microg/ml for SLN20 and SLN50, respectively. However, in PCLS we determined only SLN50 cytotoxic values with a concentration of 1500 microg/ml. The lung slices seem to be a more sensitive test system. SLN20 showed lower toxic values in all test systems. Therefore we conclude that SLN20 could be used as a suitable DDS for the lung, from a toxicological point of view.

European Journal of Pharmaceutics and Biopharmaceutics, 2005

Transcorneal in vitro permeation studies of ophthalmic drugs are normally performed with either e... more Transcorneal in vitro permeation studies of ophthalmic drugs are normally performed with either excised animal corneas or latterly corneal cell culture models. A good correlation between these models and excised animal corneas regarding permeation behaviour of drugs has already been shown. However, comparisons between corneal in vitro models containing human cells and excised human corneas do not exist yet. Therefore in the present study the transcorneal permeation of six different model drugs (pilocarpine hydrochloride, befunolol hydrochloride, hydrocortisone, diclofenac sodium, clindamycin hydrochloride and timolol maleate) across our previously described three-dimensional organotypic human cornea construct (HCC) was tested using Franz diffusion cells and compared with permeation data obtained from human donor corneas. The HCC showed a similar permeation behaviour compared with human donor cornea for all substances. The permeabilities (permeation coefficients P) of the human cornea equivalent versus the human donor cornea were the same in the case of diclofenac, clindamycin, timolol, but marginally decreased for hydrocortisone and slightly increased for pilocarpine and befunolol. These small differences of permeation coefficients were expressed as factors and only varied from 0.8 to 1.4. The results indicate that the HCC may be an alternative for in vitro permeation studies and appropriate for predicting drug absorption into the human eye.

European Journal of Pharmaceutics and Biopharmaceutics, 2003

Lipid nanoparticles (LNP) can be prepared by rapidly injecting a solution of solid lipids in wate... more Lipid nanoparticles (LNP) can be prepared by rapidly injecting a solution of solid lipids in water-miscible solvents or a water-miscible solvent mixture into water. The aim of the present study was to evaluate the potential of this method for the preparation of LNP and the physicochemical characterization of the particles produced by this method. The results show that solvent injection is a potent and versatile approach for LNP preparation. Acetone, ethanol, isopropanol and methanol are suitable solvents in contrast to ethylacetate with which no LNP could be prepared. The obtained particle sizes (z-average) were between 80 and 300 nm depending on the preparation conditions. Up to 96.5% of the employed lipid was directly transformed into LNP. The LNP formation process seems to be diffusion controlled. Physicochemical characterization of the particles by differential scanning calorimetry (DSC), transmission electron microscopy and X-ray diffraction analysis reveals a distinct decrease in crystallinity of the colloidal lipid in comparison to the bulk lipid. Furthermore, DSC analysis of LNP hints at a delayed recrystallization of the colloidal lipid and the presence of two modifications. Therefore, a certain physical instability of the LNP has to be considered.

European Journal of Pharmaceutics and Biopharmaceutics, 2005

Solid lipid nanoparticles (SLN), an alternative colloidal drug delivery system to polymer nanopar... more Solid lipid nanoparticles (SLN), an alternative colloidal drug delivery system to polymer nanoparticles, emulsions and liposomes, are generally produced by high pressure melt-emulsification. However, the harsh production process is not applicable for formulations containing shear and temperature sensitive compounds. For that reason, subsequent adsorptive SLN loading might be a promising alternative. The aim of the present study was the development and characterisation of surface-modified SLN for adsorptive protein loading by variation of both the lipid matrix and the emulsifier concentration in the continuous phase. Variations in SLN composition resulted in particle sizes between 674 and 61 nm corresponding to specific surfaces of 4.5 m 2 /g and 48.9 m 2 /g and zeta potentials between K23.4 mV and K0.9 mV. In dependence of SLN surface properties, albumin payload ranged from 2.5 to 15%. Thermoanalysis, X-ray diffraction and electron microscopy revealed anisometrical and crystalline particles. In vitro cytotoxicity was low in terms of both haemolysis, which was between 1 and 2%, and neutral red test (NRT) showing a half lethal dose between 1.1 and 4.6%.

European Journal of Pharmaceutics and Biopharmaceutics, 2010

Inhalation is a non-invasive approach for both local and systemic drug delivery. This study aimed... more Inhalation is a non-invasive approach for both local and systemic drug delivery. This study aimed to define the therapeutic window for solid lipid nanoparticles (SLNs) as a drug delivery system by inhalation from a toxicological point of view. To estimate the toxic dose of SLNs in vitro, A549 cells and murine precision-cut lung slices (PCLS) were exposed to increasing concentrations of SLNs. The cytotoxic effect of SLNs on A549 cells was evaluated by MTT and NRU assays. Viability of lung tissue was determined with WST assay and by life/dead staining using calcein AM/EthD-1 for confocal microscopy (CLSM) followed by quantitative analysis with IMARIS. Inflammation was assessed by measuring chemokine KC and TNF-a levels. The in vivo effects were determined in a 16-day repeated-dose inhalation toxicity study using female BALB/c mice, which were daily exposed to different concentrations of SLN30 aerosols (1-200 lg deposit dose). Local inflammatory effects in the respiratory tract were evaluated by determination of total protein content, LDH, chemokine KC, IL-6, and differential cell counts, performed on days 4, 8, 12, and 16 in bronchoalveolar lavage fluid. Additionally, a histopathological evaluation of toxicologically relevant organs was accomplished. The in vitro and ex vivo dose finding experiments showed toxic effects beginning at concentrations of about 500 lg/ml. Therefore, we used 1-200 lg deposit doses/animal for the in vivo experiments. Even after 16 days of challenge with a 200-lg deposit dose, SLNs induced no significant signs of inflammation. We observed no consistent increase in LDH release, protein levels, or other signs of inflammation such as chemokine KC, IL-6, or neutrophilia. In contrast, the particle control (carbon black) caused inflammatory and cytotoxic effects at corresponding concentrations. These results confirm that repeated inhalation exposure to SLN30 at concentrations lower than a 200lg deposit dose is safe in a murine inhalation model.

European Journal of Pharmaceutics and Biopharmaceutics, 2002

Dilution of semisolid preparations, in order to tailor the formulations to the needs of the patie... more Dilution of semisolid preparations, in order to tailor the formulations to the needs of the patients, was thought to be associated with a number of dangers, one of which is the unpredictable alteration of activity. In the present study the influence of dilution on hydrocortisone permeation through excised human stratum corneum was investigated. The permeation profiles of hydrocortisone from various cream bases (diluted and undiluted) were found to be very similar with no significant differences. This result was in accordance with the lack of interaction between the tested bases and the structure of stratum corneum as shown by differential scanning calorimetry experiments. Thus, the permeability of stratum corneum, which was not affected by the cream bases, is the rate limiting step for drug permeation. However, it could be shown that dilution of Soventol cream (placebo with 1% hydrocortisone) which is known to contain isopropyl myristate as permeation enhancer reduces drug permeation. The reduced hydrocortisone permeation is believed to be due to reduced enhancer concentration.