Impact of drug particle shape on permeability and cellular uptake in the lung.

The generation of inhalable sized particles (1-5 µm) usually involves a particle-processing step; most commonly milling but spray drying has shown to be a suitable alternative. Besides particle size, processing may affect other particle properties, like shape and solid-state. For example, spray drying of salbutamol sulphate leads to spherical shaped predominantly amorphous particles whereas jet milling frequently maintains the irregular shape and the crystallinity of the raw material. The aim of the present study was to investigate whether particle properties, especially shape, change the biological action of the inhaled particles as well. Therefore, highly water soluble salbutamol sulphate and poorly water soluble budesonide were compared regarding dissolution, permeation and preferential uptake by epithelial cells compared to macrophages after jet milling and spray drying. For both drugs the spray dried, predominantly amorphous, particles resulted in lower respirable fractions, but higher permeability and cell uptake rates compared to the needle shaped, predominantly crystalline particles. The distinct particle properties did not affect the dissolution behaviour of salbutamol sulphate. In turn for drugs with lower solubility (budesonide), spray dried particles dissolved slower compared to jet milled particles. Preferential uptake by macrophages was higher for spray dried particles, suggesting that processing may improve targeted delivery. The comparison between murine cell lines and human monocyte derived macrophages primary cells showed similar trends in rate and preference of particle uptake.

Nano-sized and micro-sized polystyrene particles affect phagocyte function.

Adverse effect of nanoparticles may include impairment of phagocyte function. To identify the effect of nanoparticle size on uptake, cytotoxicity, chemotaxis, cytokine secretion, phagocytosis, oxidative burst, nitric oxide production and myeloperoxidase release, leukocytes isolated from human peripheral blood, monocytes and macrophages were studied. Carboxyl polystyrene (CPS) particles in sizes between 20 and 1,000 nm served as model particles. Twenty nanometers CPS particles were taken up passively, while larger CPS particles entered cells actively and passively. Twenty nanometers CPS were cytotoxic to all phagocytes, ≥500 nm CPS particles only to macrophages. Twenty nanometers CPS particles stimulated IL-8 secretion in human monocytes and induced oxidative burst in monocytes. Five hundred nanometers and 1,000 nm CPS particles stimulated IL-6 and IL-8 secretion in monocytes and macrophages, chemotaxis towards a chemotactic stimulus of monocytes and phagocytosis of bacteria by macrophages and provoked an oxidative burst of granulocytes. At very high concentrations, CPS particles of 20 and 500 nm stimulated myeloperoxidase release of granulocytes and nitric oxide generation in macrophages. Cytotoxic effect could contribute to some of the observed effects. In the absence of cytotoxicity, 500 and 1,000 nm CPS particles appear to influence phagocyte function to a greater extent than particles in other sizes.

Evidence of a dietary selection for methionine by the piglet.

The objective of the current study was to investigate if there is a preference of piglets for diets varying in Met content and whether these preferences change with time. For this purpose, a feeding trial was carried out over a period of 6 wk. Piglets (equal numbers of males and females) with an initial BW of 7.2 +/- 0.1 kg were randomly subdivided into 4 groups of 12 pigs each. Two reference groups were fed either 0.19% Met (low-Met group) or 0.26% Met (high-Met group) diets. Two other groups had the choice between 2 diets containing 0.19 or 0.23% Met (Met-choice 1 group), or 0.19 or 0.26% Met (Met-choice 2 group). Compared with the low-Met group (397 g), daily feed intake was increased by 43%, 60%, and 82% (P < 0.05) in the Met-choice 1, Met-choice 2, and the high-Met group, respectively. Piglets on the Met-choice 1 and Met-choice 2 groups, respectively, selected 72 and 80% of the higher Met diet. In the first week, piglets on both Met-choice groups selected the diets at random, but they increased their preference for the diets higher in Met up to 81 and 89%, respectively, in the last experimental week. For the total experiment, mean Met contents of total diets were 0.22 and 0.25% in the Met-choice 1 and Met-choice 2 groups, respectively. Average daily gain of 195 g in the low-Met group was more than doubled (P < 0.05) in the high-Met group. Daily gains of 306 and 366 g in the Met-choice 1 and 2 groups, respectively, were (P < 0.05) improved compared with the low-Met group but lower (P < 0.05) than in the high-Met group. Plasma Met concentration of 46.3 micromol/mL in the Met-choice 2 group was greater than in the low-Met or the Met-choice 1 groups (25.3 and 32.8 micromol/mL, respectively) but lower (P < 0.05) compared with the high-Met group (59.6 micromol/mL). Conversely, the sum of essential AA showed a greater (P < 0.05) concentration in plasma from pigs on the low-Met and Met-choice 1 groups than in plasma from pigs on Met-choice 2 group and the high-Met group. In conclusion, the present data demonstrate that piglets are able to discriminate among diets of varying Met content. When given a choice, they prefer a diet better balanced for Met to a Met-deficient diet. As a result of the altered feeding pattern, piglets are able to partly redress the depressed performance and altered plasma AA pattern resulting from the ingestion of the diet more limiting in Met concentration.

[Digital planimetry for long-term follow-up of glaucomatous optic disk injuries in patients with normal pressure glaucoma]. / Digitale Planimetrie zur Langzeitverlaufskontrolle der glaukomatösen Papillenschäden bei Patienten mit Normaldruckglaukom.

BACKGROUND: Aim of the study was to evaluate the validity of quantitative planimetry of the optic disc with a new digital method and to assess the correlation of the measurements with morphological changes in eyes with low tension glaucoma. MATERIAL AND METHODS: The study included 40 eyes from 40 patients (age 61+/-12 years) with low tension glaucoma with a mean follow-up of 4.9+/-2.1 (range 3-9) years. All patients underwent annually complete ophthalmological examination including 15 degrees color optic disc photographs and automated white-white visual fields. RESULTS: Out of 40 eyes morphological examination showed signs of progression in 18 eyes and in 22 eyes no morphological changes of the optic disc were detected The digital planimetrically measured optic disc area did not vary between the first and the last photos. The mean differences between measured values for optic disc area between two examinations were 0.027+/-0.071 mm(2) and the reliability coefficient (Cronbachs alpha) was 0.99. Neuroretinal rim area decreased statistically highly significantly in eyes with morphological progression, and in eyes without morphological changes decreased only slightly. CONCLUSIONS: The variation of measurements of the optic disc area can be minimized by consideration and adjustment of the individual image magnification of the photos using digital planimetry. This method allows the quantitative assessment even of slight changes of the neuroretinal rim area and is a useful examination for follow-up of glaucoma patients.