Biomedical subjects

C C Müller-Goymann

Publications and source records attributed to C C Müller-Goymann.

At least 19 recordsLinked to original sources

PubMed2006

Investigation of surface-modified solid lipid nanocontainers formulated with a heterolipid-templated homolipid.

There is increasing interest in the search for improved drug delivery systems with greater versatility. Consequently, many drug delivery systems have been studied. In this study, surface-modified lipid nanocontainers were formulated with a homolipid from Capra hircus (goat fat) templated with a heterolipid (Phospholipon 90G) which was also the surface modifier. The solid lipid nanocontainers (SLN) were formulated by hot high pressure homogenisation using increasing concentrations of polysorbate 80 as the mobile surfactant. Prior to SLN preparation, the templated homolipid was formulated by fusion to obtain a homogeneous lipid matrix, which was characterized using differential scanning calorimetry (DSC), polarized light microscopy (PLM) and wide angle X-ray diffraction (WAXD) to obtain its thermal and crystal characteristics. Isothermal heat conduction microcalorimetry (IMC) and freeze-fracture transmission electron microscopy (FFTEM) studies were carried out on the templated homolipid and SLN containing 1.0% (w/w) of polysorbate 80 to study their in situ crystallization kinetics and morphology, respectively. The formulated SLN were also subjected to time-resolved DSC, WAXD and particle size analyses for one month. The thermal and crystal characteristics were compared with those of the bulk lipid matrix (templated homolipid). Result of the particle size analysis indicated that the particles size remained roughly within the lower nanometer range after one month. FFTEM micrograph of the lipid matrices revealed lamellar sheets for Phospholipon 90G and layered triglyceride structures for the homolipid and Phospholipon 90G-templated homolipid. FFTEM micrograph of SLN revealed anisometric structures. PLM of the templated homolipid did not show, but goat fat (homolipid) alone showed slight growth in crystals with time. WAXD and DSC studies revealed minor increase in crystallinity of the new lipid matrix after one month and DSC also detected templation of homolipid by the heterolipid noted by the disappearance of the lower melting peak of the homolipid. However, for the SLN, WAXD results showed low crystalline particles while DSC only showed a very little endothermic process after one month of storage at 20 degrees C. The implication of this finding is that progression of the SLN to highly ordered particles over time would not occur. This will be favourable for any incorporated drug as drug expulsion, due to increase in crystallinity, will not occur. Result obtained from analysis of the isothermal crystallization exotherms indicated that the templated homolipid and SLN1 containing 1.0% polysorbate 80 possess similar nucleation mechanisms and growth dimensions different from the pure homolipid. The SLN containing 0.5 and 1.0% polysorbate 80 possessed good properties and could prove to be good delivery systems for drugs for parenteral or ocular administration. The result of this study also shows a method of improving natural lipids for use in particulate drug delivery systems.

Adipose Tissue↗

PubMed2006

In vitro erythemal UV-A protection factors of inorganic sunscreens distributed in aqueous media using carnauba wax-decyl oleate nanoparticles.

This paper describes the in vitro photoprotection in the UV-A range, i.e. 320-400 nm obtained by the use of carnauba wax-decyl oleate nanoparticles either as encapsulation systems or as accompanying vehicles for inorganic sunscreens such as barium sulfate, strontium carbonate and titanium dioxide. Lipid-free inorganic sunscreen nanosuspensions, inorganic sunscreen-free wax-oil nanoparticle suspensions and wax-oil nanoparticle suspensions containing inorganic sunscreens dispersed either in their oil phase or their aqueous phase were prepared by high pressure homogenization. The in vitro erythemal UV-A protection factors (EUV-A PFs) of the nanosuspensions were calculated by means of a sun protection analyzer. EUV-A PFs being no higher than 4 were obtained by the encapsulation of barium sulfate and strontium carbonate, meanwhile by the distribution of titanium dioxide in presence of wax-oil nanoparticles, the EUV-A PFs varied between 2 and 19. The increase in the EUV-A PFs of the titanium dioxide obtained by the use of wax-oil nanoparticles demonstrated a better performance of the sun protection properties of this pigment in the UV-A region.

Barium Sulfate↗

PubMed2006

Further characterization of theobroma oil-beeswax admixtures as lipid matrices for improved drug delivery systems.

There is an increasing interest in lipid based drug delivery systems due to factors such as better characterization of lipidic excipients and formulation versatility and the choice of different drug delivery systems. It is important to know the thermal characteristics, crystal habit, texture, and appearance of a new lipid matrix when determining its suitability for use in certain pharmaceutical application. It is line with this that this research was embarked upon to characterize mixtures of beeswax and theobroma oil with a view to applying their admixtures in drug delivery systems such as solid lipid nanoparticles and nanostructured lipid carriers. Admixtures of theobroma oil and beeswax were prepared to contain 25% w/w, 50% w/w, and 75% w/w of theobroma oil. The admixtures were analyzed by differential scanning calorimetry (DSC), small angle X-ray diffraction (SAXD), wide angle X-ray diffraction (WAXD), and isothermal heat conduction microcalorimetry (IMC). The melting behavior and microstructures of the lipid admixtures were monitored by polarized light microscopy (PLM). Transmission electron microscopy (TEM) was used to study the internal structures of the lipid bases. DSC traces indicated that the higher melting peaks were roughly constant for the different admixtures, but lower melting peaks significantly increased (p < 0.05). The admixture containing 25% w/w of theobroma oil possessed highest crystallinity index of 95.6%. WAXD studies indicated different reflections for the different lipid matrices. However, new interferences were detected for all the lipid matrix admixtures between 2theta = 22.0 degrees and 2theta = 25.0 degrees. The lipid matrices containing 50% w/w and 25% w/w of theobroma oil showed absence of the weak reflection characteristic of pure theobroma oil, while there was disappearance of the strong intensity reflection of beeswax in all the lipid matrix admixtures at all stages of the study. PLM micrographs revealed differences with regard to the thermal and optical behaviors depending on the composition of the matrix. The lipid matrix consisting of 75% w/w of theobroma oil showed a spherulite texture after 4 weeks of isothermal storage. Crystallization exotherms of lipid matrices containing 50% w/w and 25% w/w of theobroma oil showed change in modification after 30 min with the latter having a greater time-dependent crystallization. Generally, low non-integral Avrami exponents and growth rate constants were obtained for all the lipid matrices, with the admixture containing 25% w/w theobroma oil having the lowest Avrami exponent and growth rate constant. Based on the results obtained, admixtures containing 50% w/w and 75% w/w of theobroma oil could be applied in the formulation of solid lipid nanoparticles and nanostructured lipid carriers as these lipid matrices possessed crystal characteristics that favour such drug delivery systems.

Cacao↗

PubMed2006

Sun protection enhancement of titanium dioxide crystals by the use of carnauba wax nanoparticles: the synergistic interaction between organic and inorganic sunscreens at nanoscale.

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).

Calorimetry, Differential Scanning↗

PubMed2006

A critical study of novel physically structured lipid matrices composed of a homolipid from Capra hircus and theobroma oil.

There is increasing interest in drug formulation using lipids. In this study, some physically structured lipid matrices were formulated and characterized for drug delivery applications. Lipid matrices containing a novel homolipid from Capra hircus (goat fat) and theobroma oil, at 25, 50 and 75% (w/w) concentration of the homolipid were formulated by fusion. The lipid matrices were subjected to some characterization procedures such as differential scanning calorimetry (DSC) to ascertain their supramolecular properties, small angle X-ray diffraction (SAXD), wide angle X-ray diffraction (WAXD), polarized light microscopy (PLM) and isothermal heat conduction microcalorimetry (IMC). The internal structures of some selected lipid matrices were also studied by freeze-fracture transmission electron microscopy (FFTEM). DSC results obtained indicated that goat fat has a pre-transition at 15.9 +/- 0.2 degrees C (after 1 week) and melts completely with two detectable melting peaks at 33.0 +/- 0.2 and 49.9 +/- 0.1 degrees C, and total enthalpy of 99.9 +/- 2.5 mJ/mg determined after 6 weeks of preparation. The melting enthalpy of goat fat changed after 3 weeks but remained constant after 6 weeks while the melting enthalpy of the lipid matrix containing 50% (w/w) goat fat changed after 3 and 6 weeks. An increase in lower melting peak was observed in the lipid matrix containing 25% (w/w) goat fat after 6 weeks. WAXD and SAXD of the physically structured lipid matrices showed reflections of the different pure lipids but new interferences were detected in WAXD mostly between 2theta=17.5 degrees and 2theta=27.5 degrees . PLM observation revealed the presence of Maltese crosses for the homolipid at 37 degrees C, which disappeared upon heating at 51.0 degrees C. PLM of the structured lipid matrix containing 25% (w/w) goat fat showed distinct crystal growth after 4 weeks among the admixtures. However, IMC studies did not reveal any change in recrystallization behaviour in this lipid matrix within 24 h. Analysis of the crystallization exotherms indicated that the lipid matrix containing 50% (w/w) goat fat showed unique crystallization kinetics and possessed the lowest Avrami exponent, while goat fat alone showed slight change within the first 45 min of isothermal crystallization. Physically structured lipid matrix containing 75% (w/w) goat fat possessed the lowest growth rate constant.

Adipose Tissue↗

PubMed2006

Physical stability, centrifugation tests, and entrapment efficiency studies of carnauba wax-decyl oleate nanoparticles used for the dispersion of inorganic sunscreens in aqueous media.

Aqueous nanoscale lipid dispersions consisting of carnauba wax-decyl oleate mixtures acting as carriers or accompanying vehicles for inorganic sunscreens such as barium sulfate, strontium carbonate, and titanium dioxide were prepared by high pressure homogenization. For the manufacture of these nanosuspensions, three pigment concentrations (%wt), namely 2, 4, and 6, and two carnauba wax-decyl oleate ratios, 1:1 and 2:1, were used, being some of these combinations chosen for stability studies. Six-month physical stability tests at 4, 20, and 40 degrees C selecting the mean particle size and the polydispersity index of the nanosuspensions as reference parameters were performed. Centrifugation tests of the nanosuspensions assessed by transmission electron microscopy and by the determination of the content of pigments and carnauba wax in the separated fractions were done. The mean particle sizes and the polydispersity indices of the nanosuspensions were not altered after six-month storages at 20 and at 40 degrees C. However, the storage of those at 4 degrees C considerably increased the particle size and polydispersity of the systems, particularly when wax-oil ratios (2:1) were used for the entrapment of the pigments. Transmission electron micrographs of centrifuged samples denoted the presence of three major fractions showing the different types of particles integrated into the nanosuspensions. Furthermore, it was observed that not all the carnauba wax participated in the entrapment of the pigment. Regarding the amount of pigment being encapsulated or bonded by the wax-oil matrices, entrapment efficiencies higher than 85.52% were reported.

Centrifugation↗

PubMed2006

Artificial sun protection: sunscreens and their carrier systems.

The formulation of sunscreens products requires information about the properties of the substances responsible for the sun protection, their action mechanisms and the vehicles used for their administration. The improvement of the performance of sunscreen substances by a modification of their chemical, physical and technological properties or by the use of conventional and novel carriers is described in this review. The sun protection achieved by the use of sunscreens incorporated into carriers in terms of the sun protection factor (SPF) and other performance indices is also shown. Current manufacturing methods to incorporate sunscreen substances into vehicles are briefly described. Furthermore, basic information related to the dermatological effects of the UV radiation classified according to the different spectral regions of the UV radiation is presented in this manuscript.

Drug Carriers↗

PubMed2005

Drug release and permeation studies of nanosuspensions based on solidified reverse micellar solutions (SRMS).

Solidified reverse micellar solutions (SRMS), i.e. mixtures of lecithin and triglycerides, offer high solubilisation capacities for different types of drugs in contrast to simple triglyceride systems [Friedrich, I., Müller-Goymann, C.C., 2003. Characterisation of SRMS and production development of SRMS-based nanosuspensions. Eur. J. Pharm. Biopharm. 56, 111-119]. Nanosuspensions based on SRMS were prepared by homogenisation close to the melting point of the SRMS matrix. In a first step the SRMS matrices of 1:1 (w/w) ratios of lecithin and triglycerides were loaded with 17beta-estradiol-hemihydrate (EST), hydrocortisone (HC) or pilocarpine base (PB), respectively, and subsequently ground in liquid nitrogen to minimise drug diffusion later on. The powder was then dispersed in a polysorbate 80 solution using high pressure homogenisation. The drug loading capacities of the nanosuspensions were very high in the case of poorly water-soluble EST (99% of total 0.1%, w/w, EST) and HC (97% of total 0.5%, w/w, HC) but not sufficient with the more hydrophilic PB (37-40% of total 1.0%, w/w, PB). These findings suggest SRMS-based nanosuspensions to be promising aqueous drug carrier systems for poorly soluble drugs like EST and HC. Furthermore, in vitro drug permeation from the different drug-loaded nanosuspensions was performed across human cornea construct (HCC) as an organotypical cell culture model. PB permeation did not differ from the nanosuspension and an aqueous solution whereas the permeation coefficients of HC-loaded nanosuspensions were reduced in comparison to aqueous and oily solutions of HC. However, the permeated amount was higher from the nanosuspensions due to a much lower HC concentration in the solution than that in the nanosuspension (solution 0.02%, w/w, versus nanosuspension 0.5%, w/w). The high drug load of the nanoparticles provides prolonged HC release. Permeated amounts of EST were reduced in comparison to HC and only detectable with an ELISA technique. The EST release from nanosuspensions and different EST-loaded systems revealed a prolonged EST release from the nanoparticulate systems in contrast to a faster release of an oily solution of an equal EST concentration. With regard to an aqueous EST suspension of similar concentration which represents a depot system the release rate from the nanosuspensions revealed the same order of magnitude which points again to a prolonged release potential of the nanosuspensions.

Cell Line↗

PubMed2005

Thermal analysis of the crystallization and melting behavior of lipid matrices and lipid nanoparticles containing high amounts of lecithin.

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 beta-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 beta-modification. In comparison to the undispersed LM, the crystallization temperature of LNP is significantly decreased by about 20 degrees C whereas the melting point is reduced by about 5 degrees 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.

Calorimetry, Differential Scanning↗

PubMed2005

Novel nanoparticulate carrier system based on carnauba wax and decyl oleate for the dispersion of inorganic sunscreens in aqueous media.

The purpose of this study was to characterize carrier systems for inorganic sunscreens based on a matrix composed of carnauba wax and decyl oleate. Ultraviolet radiation attenuators like barium sulfate, strontium carbonate and titanium dioxide were tested. The lipid matrices were used either as capsules or as accompanying vehicles for the pigments in aqueous dispersions. Manufacturing was performed using high pressure homogenization at 300bar and a temperature of 75 degrees C. To evaluate the effect of the pigments on the crystalline structure of the wax-oil mixture, X-ray diffraction and differential scanning calorimetry were used. Further parameters determined were particle size, polydispersity index, z-potential, viscosity and sun protection factor (SPF). Transmission electron microscopy was also applied for visualization of nanoparticles. The X-ray diffraction patterns and the melting points of the lipid mixtures remained unchanged after the pigments were added. The particle sizes of the encapsulated species ranged from 239 to 749.9nm showing polydispersity values between 0.100 and 0.425. Surface charge measurements comprising values up to -40.8mV denoted the presence of stable dispersions. The formulations could be described as ideal viscous presenting viscosities in a range of 1.40-20.5mPas. Significant increases in SPF up to about 50 were reported after the encapsulation of titanium dioxide. Freeze fracture micrographs confirmed the presence of encapsulated inorganic crystals.

Absorptiometry, Photon↗

PubMed2005

[Esterase activity of human organotypic cornea construct (HCC) as in vitro model for permeation studies].

Organotypic cornea equivalents are used as in vitro models for permeation studies. Many ophthalmic drugs are applied as ester prodrugs to achieve a higher bioavailability. The esterase activity of three corneal human cell lines (epithelial, stromal, endothelial cells) as well as of excised porcine cornea, human donor cornea and human cornea construct (HCC) was investigated and compared. Esterase activity was determined using p-nitrophenyl acetate and hydrocortisone acetate (HCA) as esterase substrates. Hydrocortisone acetate permeation across porcine cornea, human donor cornea and HCC was studied in vitro using Franz-diffusion cells. Corneal epithelial cells showed the highest esterase activity and only small differences to keratocytes and endothelial cells were detectable. The permeation barrier properties of the different corneal tissues were very similar in the case of HCA permeation whereas HCA metabolism rates were in the ranking order of porcine cornea > HCC > human donor cornea. Permeation and metabolism studies indicate that the in vitro permeation model HCC is able to adequately convert hydrocortisone acetate to hydrocortisone.

Aged↗

PubMed2005

Characterisation of surface-modified solid lipid nanoparticles (SLN): influence of lecithin and nonionic emulsifier.

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 -23.4 mV and -0.9 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%.

Cell Survival↗

PubMed2005

An attempt to clarify the influence of glycerol, propylene glycol, isopropyl myristate and a combination of propylene glycol and isopropyl myristate on human stratum corneum.

The present study is a comparison of the influences of glycerol, propylene glycol (PG), isopropyl myristate (IPM) and a combination of PG and IPM (1/1; w/w) on human stratum corneum (SC) by means of differential scanning calorimetry (DSC) and wide and small angle X-ray-diffraction (WAXD and SAXD). The effects of glycerol and PG on SC structure can be attributed to their functional groups. In DSC transition temperatures of lipid fractions are decreased whereas SAXD long distances of lamellar phases reveal an additional interference due to an integration into hydrophilic regions of hexagonally packed lipids (PG) or orthorhombically packed lipids (glycerol). The increased repeat distance is attributed to the polar character of both molecules. However, with IPM the long distance remains unaffected. IPM is integrated into the lipophilic regions of SC lipid matrix as concluded from an increase of WAXD reflections of orthorhombical lipids and a decrease of WAXD reflections of hexagonal lipids. The combination of PG/IPM affects SC microstructure in a specific manner. DSC shows a decrease in transition temperatures of the lipid fractions, although not as much as expected from the single substances. Additionally, the combination of IPM/PG affects the short distances of orthorhombically and hexagonally packed lipids in WAXD measurements similar as PG alone, whereas the long distance seems to remain unaffected as in the case of IPM pretreatment. Adjuvants with penetration enhancing potential reveal different effects on SC lipid microstructure, which have to be kept in mind in terms of formulating systems for transdermal administration.

Calorimetry, Differential Scanning↗

PubMed2005

Use of artificial skin constructs in permeation studies of clindamycin phosphate.

Penetration and permeation of topically applied substances may be studied in vitro either by using excised human and animal skin or with a 3-dimensional artificial skin construct (ASC). In the present study, ASC consisting of dermal and epidermal layers were cultivated with human dermal fibroblasts and spontaneously transformed human epidermal cells from the HaCaT-cell line. For comparative purposes the permeation barrier of ASC was also evaluated using a commercial skin model (AST-2000). Higher drug permeabilities were achieved with ASC in comparison with excised human stratum corneum (EHSC). The factors between permeation coefficients of ASC and EHSC depend on the respective drugs and also on different types of the formulation. Due to higher permeation coefficients obtained, the running time of the experiments could be reduced in the case of ASC. A further advantage of ASC is the independency of skin donations. Additionally, cultivation of ASC for the use in permeation studies is possible in advance, because storage conditions under nitrogen freezing do not affect ASC quality negatively.

Anti-Bacterial Agents↗

PubMed2004

Physicochemical characterization of colloidal drug delivery systems such as reverse micelles, vesicles, liquid crystals and nanoparticles for topical administration.

Topical administration of cosmetics and pharmaceuticals involves a variety of different formulations of which colloidal drug carrier systems are currently of particular interest. After a short introduction of reverse micellar solutions, liquid crystals, vesicles and nanoparticles, appropriate methods of physicochemical characterization are introduced including X-ray diffraction, laser light scattering, electron microscopy, and differential scanning calorimetry. Emphasis is laid on topical applications of the colloidal drug delivery systems (DDS) covered, with the main objective of both sustained drug release and improved stability of DDS.

Chemical Phenomena↗

PubMed2004

Human corneal equivalent as cell culture model for in vitro drug permeation studies.

AIMS: For the study of transcorneal in vitro permeation of ophthalmic drugs, excised animal cornea or corneal epithelial cell culture are frequently used as a replacement for the human cornea. The main purposes of this study were to reconstruct a complete human organotypic cornea equivalent, consisting of all three different cell types (epithelial, stromal, and endothelial); to test the barrier function of this bio-engineered human cornea using three different model drugs (pilocarpine hydrochloride (PHCl), befunolol hydrochloride (BHCl), and hydrocortisone (HC)); and to determine its usefulness as an in vitro model for prediction of ocular drug absorption into the human eye. METHODS: A multilayer tissue construct was created step by step in Transwell cell culture insert using SV-40 immortalised human endothelial and epithelial cells and native stromal cells (fibroblasts). Morphology was characterised by light microscopy using routine H&E staining. Scanning electron microscopy was used to evaluate ultrastructural features. Ocular permeation of drugs across the human cornea construct was tested using modified Franz cells and compared with data obtained from excised porcine cornea and previously described porcine cornea constructs. RESULTS: and conclusion: The cornea construct exhibited typical corneal structures such as a monolayer of hexagonally shaped endothelial cells and a multilayered epithelium consisting of seven to nine cell layers with flat superficial cells. The formation of microplicae and microvilli was also confirmed. The human cornea construct showed similar permeation behaviour for all substances compared with excised porcine cornea. However, permeability (permeation coefficients K(p)) of the human cornea equivalent (PHCl 13.4*10(-6) (SD 3.01*10(-6)); BHCl 9.88*10(-6) (SD 1.79*10(-6)); HC 5.41*10(-6) (SD 0.40*10(-6)) cm/s) was about 1.6-1.8 fold higher than excised porcine cornea. Compared with data from the porcine cornea construct the cultivated human equivalent showed a decreased permeability. The reconstructed human cornea could be appropriate to predict drug absorption into the human eye.

Adrenergic beta-Antagonists↗

PubMed2004

Cultivation and characterization of a bovine in vitro model of the cornea.

The aim of this study was to develop an in vitro model of the cornea of bovine cells, to characterise the model by histochemical methods and to investigate permeation of ophthalmic drugs through the model. As in the in vivo situation, an in vitro model of the cornea should consist of all three different types of cells. In the current study, the construction of the in vitro cornea was performed using cells prepared from primary cultures. To investigate the state of the cells in the cultures, growth curves were established. Immunocytochemical determination of keratin and vimentin was performed for all three isolated and sub-cultivated cell types of the bovine cornea. To further simulate the in vivo conditions, corneal epithelial cells were seeded onto the collagen-gel base containing the stromal cells with an underlying sheet of endothelium. Permeation experiments were performed with pilocarpine hydrochloride and timolol hydrogen maleate as model drugs and excised bovine cornea and the in vitro cornea as permeation barriers. The immunohistochemical investigations show that excised bovine cornea and the in vitro model of the cornea are comparable with respect to the expression of keratin K3, indicating that the primarily isolated cells correspond to the different cell types of the cornea. Culturing of the epithelial cells on the complex basis has led to the formation of a corneal epithelium with several layers, closely resembling the morphology of the in vivo epithelium. Although the permeation rates of the drug through the in vitro cornea were always higher, the sequence in which the drugs permeate through the two types of barriers was the same. The drug permeation through the in vitro cornea may therefore be a useful predictive tool to estimate the permeability coefficients of drugs through excised cornea.

Adrenergic beta-Antagonists↗

PubMed2003

Solvent injection as a new approach for manufacturing lipid nanoparticles--evaluation of the method and process parameters.

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.

2-Propanol↗