Interaction of dispersed cubic phases with blood components.

The interaction of aqueous nanoparticle dispersions, e.g. based on monoolein/poloxamer 407, with blood components is an important topic concerning especially the parenteral way of administration. Therefore, the influence of human and porcine plasma on dispersed cubic phases was investigated. Particle size measurements of mixtures with plasma indicated a decrease in particle size. In cryo-transmission electron micrographs, different structures could be found, which arose from the dispersed cubic phases under plasma contact. Non-cubic structures on the particle surface were decomposed first. Several phase transitions with the formation of smaller and sometimes larger particle fractions were observed beside remaining cubic structures. A very low but detectable hemolytic activity was found for the dispersed cubic phases based on monoolein and poloxamer 407, when compared to the hemolytic activity of cubic phases based on monoolein and poloxamer 188, on soy phosphatidylcholine, glycerol dioleate and polysorbate 80 or the parenteral fat emulsion Lipofundin MCT 20%.

Skin penetration enhancement by a microneedle device (Dermaroller) in vitro: dependency on needle size and applied formulation.

This study focused on the in vitro evaluation of skin perforation using a new microneedle device (Dermaroller) with different needle lengths (150, 500 and 1500 microm). The influence of the microneedle treatment on the morphology of the skin surface (studied by light and scanning electron microscopy), on the transepidermal water loss (TEWL) and on the penetration and permeation of hydrophilic model drugs was investigated using excised human full-thickness skin. Furthermore, invasomes - highly flexible phospholipid vesicles containing terpenes and ethanol as penetration enhancer - were compared with an aqueous solution. Elevated TEWL values were measured after Dermaroller treatment compared to untreated human skin with a gradual increase of the TEWL over the first hour whereas afterwards the TEWL values decreased probably caused by a reduction of the pore size with time. Skin perforation with the Dermarollers enhanced drug penetration and permeation for both formulations tested. Invasomes were more effective to deliver hydrophilic compounds into and through the skin compared to the aqueous drug solutions and the combination with skin perforation further enhanced drug penetration and permeation. In conclusion, Dermarollers being already commercially available for cosmetic purposes appear also promising for drug delivery purposes particularly those with medium (500 microm) and shorter (150 microm) needle lengths.

Influence of preparation conditions and heat treatment on the properties of supercooled smectic cholesteryl myristate nanoparticles.

Colloidal dispersions of cholesterol esters in the supercooled smectic state are under investigation as a novel drug carrier system in particular with respect to parenteral application. In the present study, suitable conditions for the homogenization of cholesteryl myristate dispersions stabilized with a phospholipid/bile salt blend were evaluated. For effective particle size reduction homogenization with high pressure and at temperatures above the melting temperature of the cholesterol ester (isotropic melt) is necessary. Homogenization at lower temperature where the matrix lipid is in the smectic state is less effective even when applying the highest homogenization pressure possible but still leads to dispersions with particles in the colloidal size range. Since sterility is required for parenteral medications and is usually achieved by autoclaving for aqueous systems, the physical and chemical stability of cholesteryl myristate nanoparticles stabilized with different surface active agents during heat treatment was investigated as well. The dispersions were characterized by particle size and zeta potential measurements, differential scanning calorimetry (DSC) and high performance thin layer chromatography (HPTLC). The results indicate that cholesteryl myristate nanoparticles stabilized with phospholipid/sodium glycocholate, polyvinyl alcohol, poloxamer and poloxamine can be sterilized by autoclaving. Compared to cholesterol ester free dispersions of phospholipids, the phospholipid seems to be more stable against hydrolysis during prolonged heat treatment in the phospholipid/bile salt containing cholesteryl myristate dispersions.

Crystallization behavior of supercooled smectic cholesteryl myristate nanoparticles containing phospholipids as stabilizers.

Supercooled smectic nanoparticles based on physiological cholesterol esters are under investigation as a potential novel carrier system for lipophilic drugs. The present study investigates the very complex crystallization behavior of such nanoparticles stabilized with the aid of phospholipids. Phospholipid and phospholipid/bile salt stabilized cholesteryl myristate dispersions were prepared by high-pressure melt homogenization and characterized by particle size measurements, differential scanning calorimetry, X-ray diffraction and electron microscopy. To obtain fractions with very small smectic nanoparticles, selected dispersions were ultracentrifuged. A mixture of cholesteryl myristate and the phospholipid used for the stabilization of the dispersions was also investigated by light microscopy. The nanoparticles usually display a bimodal crystallization event which depends on the thermal treatment and cannot be attributed to crystalline polymorphism. The ratio of the particle fractions crystallizing in the two successive steps strongly depends on the particle size of the dispersions. The presence of larger particles leads to an increased fraction crystallizing at higher temperature and a higher recrystallization tendency upon storage. The observed peculiarities of the crystallization behavior seem to be mainly caused by the presence of particles with different shapes (cylindrical and spherical) as observed in electron microscopy. Alterations in the composition of the nanoparticles may also play a role.

Supercooled smectic nanoparticles: a potential novel carrier system for poorly water soluble drugs.

PURPOSE: The possibility of preparing nanoparticles in the supercooled thermotropic liquid crystalline state from cholesterol esters with saturated acyl chains as well as the incorporation of model drugs into the dispersions was investigated using cholesteryl myristate (CM) as a model cholesterol ester. METHODS: Nanoparticles were prepared by high-pressure melt homogenization or solvent evaporation using phospholipids, phospholipid/ bile salt, or polyvinyl alcohol as emulsifiers. The physicochemical state and phase behavior of the particles was characterized by particle size measurements (photon correlation spectroscopy, laser diffraction with polarization intensity differential scattering), differential scanning calorimetry, X-ray diffraction, and electron and polarizing light microscopy. The viscosity of the isotropic and liquid crystalline phases of CM in the bulk was investigated in dependence on temperature and shear rate by rotational viscometry. RESULTS: CM nanoparticies can be obtained in the smectic phase and retained in this state for at least 12 months when stored at 230C in optimized systems. The recrystallization tendency of CM in the dispersions strongly depends on the stabilizer system and the particle size. Stable drug-loaded smectic nanoparticles were obtained after incorporation of 10% (related to CM) ibuprofen, miconazole, etomidate, and 1% progesterone. CONCLUSIONS: Due to their liquid crystalline state, colloidal smectic nanoparticles offer interesting possibilities as carrier system for lipophilic drugs. CM nanoparticles are suitable model systems for studying the crystallization behavior and investigating the influence of various parameters for the development of smectic nanoparticles resistant against recrystallization upon storage.

[Infection in the elderly--what is different?]. / Infektionen im Alter--was ist anders?

Infectious diseases are a common cause of increased morbidity and mortality in elderly patients and present a frequent problem in the geriatrician's daily practice. Infections in the elderly are quite different from infections in a younger population. These differences are due to Age-related alterations in immunology Different epidemiology and bacteriology Increased morbidity and mortality Altered clinical presentation Concommittant disability and comorbidity in many older patients Different approaches to therapy. This article is an attempt to discuss these various aspects of infectious disease in the elderly. The most important infections in the elderly are caused by bacteria. Incidence and bacterial spectrum depends on the site of infection and whether the patient is hospitalized, living in a nursing home or in the community. Pneumonia, UTI and pressure ulcer infections are more frequent in patients living in nursing homes than in community dwelling older people. Infections are a frequent cause of hospitalization in elderly people and hospitalization on the other hand is a risk factor for life-threatening nosocomial infections, caused by invasive diagnostic procedures and frequent use of urinary and venous catheters. Infections in the elderly are often accompanied by serious complications as bacteriemia (pneumonia), frequent recurrence (UTI), perforation and abscess (abdominal infections) and severe disability (pressure ulcer infections). Because of these serious and frequent complications mortality of infections is higher in older patients than in younger people. Elderly patients with infectious disease often present in the same way as younger patients do. Many elderly however present with non-specific clinical symptoms and non-specific functional decline which makes an accurate diagnosis difficult and may lead to a life-threatening delay of diagnosis and therapy. In older patients with unexplained functional decline, physicians must be aware of the possibility of a serious infection. Moreover, the physician can not rely on typical signs of infections as fever. In the elderly the fever response is often blunted even in the presence of bacteremia. Leokocytosis may be absent and elevation of acute phase protein is a more reliable marker of infection than elevation of erythrocyte sedimentation rate. Clinical suspicion of bacterial infection in elderly patient should prompt Careful anamnesis and clinical investigation Hospitalization if necessary Diagnostic procedures without delay including blood cultures Immediate empiric antibiotic therapy taking into account the site of infection, if the infection is community acquired or nosocomial and the most likely bacterial spectrum and local resistance factors. The use of broad spectrum antibiotic substances with a low side effect profile and pharmacokinetic properties which are suitable for elderly patients.