Central line-associated bloodstream infections at the multidisciplinary intensive care unit of Universitas Academic Hospital, Bloemfontein, South Africa.

Background: Central line-associated bloodstream infections (CLABSIs) are frequently encountered device-related healthcare-associated infections in critically ill patients, causing substantial morbidity, mortality and prolonged hospitalisation. Objectives: To determine the incidence of CLABSI, median catheter dwell-time prior to developing CLABSI, as well as the causative microorganisms of CLABSI among patients admitted to the multidisciplinary intensive care unit (MICU) at Universitas Academic Hospital, Bloemfontein. Methods: We conducted a retrospective review of medical and laboratory records of all MICU patients who had a central line placed between January and December 2018. Results: A total of 377 patients were admitted to the MICU in 2018, of which 182 met the inclusion criteria for the present study. From the cohort of 182 patients, 16.5% (n=30) of patients presented with 32 CLABSI episodes, with two patients having had two independent episodes each. A total of 1 215 central line days were recorded, yielding a CLABSI rate of 26.3/1 000-line days. Laboratory analysis identified microorganisms in 38 blood cultures, with Gram-negative organisms (55.3%; n=21) being predominant over Gram-positive organisms (39.5%; n=15) and fungi (5.3%; n=2). Conclusion: The incidence of CLABSI at the MICU at Universitas Academic Hospital is high. Urgent intervention with strict compliance to prevention bundles is required to reduce the high incidence of CLABSI.

Recent changes in high-mountain plant community functional composition in contrasting climate regimes.

High-mountain plant communities are strongly determined by abiotic conditions, especially low temperature, and are therefore susceptible to effects of climate warming. Rising temperatures, however, also lead to increased evapotranspiration, which, together with projected shifts in seasonal precipitation patterns, could lead to prolonged, detrimental water deficiencies. The current study aims at comparing alpine plant communities along elevation and water availability gradients from humid conditions (north-eastern Alps) to a moderate (Central Apennines) and a pronounced dry period during summer (Lefka Ori, Crete) in the Mediterranean area. We do this in order to (1) detect relationships between community-based indices (plant functional leaf and growth traits, thermic vegetation indicator, plant life forms, vegetation cover and diversity) and soil temperature and snow duration and (2) assess if climatic changes have already affected the vegetation, by determining directional changes over time (14-year period; 2001-2015) in these indices in the three regions. Plant community indices responded to decreasing temperatures along the elevation gradient in the NE-Alps and the Apennines, but this elevation effect almost disappeared in the summer-dry mountains of Crete. This suggests a shift from low-temperature to drought-dominated ecological filters. Leaf trait (Leaf Dry Matter Content and Specific Leaf Area) responses changed in direction from the Alps to the Apennines, indicating that drought effects already become discernible at the northern margin of the Mediterranean. Over time, a slight increase in vegetation cover was found in all regions, but thermophilisation occurred only in the NE-Alps and Apennines, accompanied by a decline of cold-adapted cushion plants in the Alps. On Crete, xeromorphic shrubs were increasing in abundance. Although critical biodiversity losses have not yet been observed, an intensified monitoring of combined warming-drought impacts will be required in view of threatened alpine plants that are either locally restricted in the south or weakly adapted to drought in the north.

Optical analysis of glutamate spread in the neuropil.

Fast synaptic communication uses diffusible transmitters whose spread is limited by uptake mechanisms. However, on the submicron-scale, the distance between two synapses, the extent of glutamate spread has so far remained difficult to measure. Here, we show that quantal glutamate release from individual hippocampal synapses activates extracellular iGluSnFr molecules at a distance of >1.5 µm. 2P-glutamate uncaging near spines further showed that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-Rs and N-methyl-D-aspartate (NMDA)-Rs respond to distant uncaging spots at approximately 800 and 2000 nm, respectively, when releasing the amount of glutamate contained in approximately five synaptic vesicles. The uncaging-induced remote activation of AMPA-Rs was facilitated by blocking glutamate transporters but only modestly decreased by elevating the recording temperature. When mimicking release from neighboring synapses by three simultaneous uncaging spots in the microenvironment of a spine, AMPA-R-mediated responses increased supra-additively. Interfering with extracellular glutamate diffusion through a glutamate scavenger system weakly reduced field synaptic responses but not the quantal amplitude. Together, our data suggest that the neuropil is more permissive to short-range spread of transmitter than suggested by theory, that multivesicular release could regularly coactivate nearest neighbor synapses and that on this scale glutamate buffering by transporters primarily limits the spread of transmitter and allows for cooperative glutamate signaling in extracellular microdomains.

Influence of PEG in PEG-PLGA microspheres on particle properties and protein release.

The aim of the present study was to compare different commercial available types of Poly(d,l-lactide-co-glycolide) (PLGA), multiblock copolymers of PLGA and polyethylene gylcol (PEG) as well as blends of PLGA and PEG regarding the preparation of microparticles and the release behavior of encapsulated protein. Microspheres were prepared by the solvent evaporation technique using the same conditions for each formulation. The encapsulation rate of bovine serum albumin (BSA) was unaffected by the different polymer types, and the mean was 79±4%. Microspheres composed of blends of PLGA and PEG showed a porous structure, a higher specific surface area, an inhomogenous distribution of protein and a higher release rate of BSA than microspheres consisting of PLGA, whereas the release profiles were the same. The specific surface area of microparticle formulations composed of diblock copolymers was the highest with 8.57±0.07m(2)/g emphasized by a highly porous, sponge-like structure. The triblock copolymer formulation revealed nearly spherical particles with a slightly uneven surface. Although the triblock copolymer consists of 10% PEG, the specific surface area was the lowest of all formulations. The rapid hydration due to PEG leads to a swollen matrix, which released the protein in a slow and continuous way.

Composite microparticles with in vivo reduction of the burst release effect.

The aim of this study was to develop microparticles containing nanoparticles (composite microparticles) for prolonged drug delivery with reduced burst effect in vitro and in vivo. Such composite microparticles were prepared with hydrophobic and biodegradable polymers [poly(epsilon-caprolactone), poly(lactic-co-glycolic) acid]. Ibuprofen was chosen as the model drug, and microparticles were prepared by the extraction technique with ethyl acetate as the solvent. Nanoparticles and microparticles and an ibuprofen solution (Pedea) were administered subcutaneously at the dose of 1 mg of ibuprofen per kg to overnight-fasted rats (male Wistar). Composite microparticles showed prolonged ibuprofen release and less burst effect when compared to simple microparticles (without nanoparticles inside) or nanoparticles both in vitro (PBS buffer) and in vivo. Moreover, ibuprofen was still detected in the plasma after 96 h with composite microparticles. Consequently, it has been demonstrated that composite microparticles were able to reduce burst release and prolong the release of ibuprofen for a long period of time.

Effect of the microencapsulation of nanoparticles on the reduction of burst release.

The initial burst release is one of the major problems in the development of controlled release formulations including drug-loaded micro- and nanoparticles, especially with low molecular weight drugs. The objective of the present work was to encapsulate, by the W/O/W emulsion, polymeric nanoparticles into polymeric microparticles by using non-water soluble polymers and appropriate organic solvents for the preparation of these composite microparticles. They were characterized in vitro (encapsulation efficiency, mean diameter and release kinetics) and compared with nanoparticles and classical microparticles prepared by the same method. Poly-epsilon-caprolactone (PCL) dissolved in methylene chloride was used to make nanoparticles, whereas ethylcellulose and Eudragit RS dissolved in ethyl acetate, a non-solvent of poly-epsilon-caprolactone, were used for the preparation of microparticles. Ibuprofen and triptorelin acetate were chosen as lipophilic and hydrophilic model drugs, respectively. High entrapment efficiencies were obtained with ibuprofen whereas lower amounts of triptorelin acetate were encapsulated, mainly with formulations prepared with poly-epsilon-caprolactone and Eudragit RS used alone or blended with ethylcellulose. The burst was significantly lower with composite microparticles and may be explained by the slower diffusion of the drugs through the double polymeric wall formed by the nanoparticle matrix followed by another diffusion step through the microparticle polymeric wall.

In vivo evaluation of lipid nanocapsules as a promising colloidal carrier for paclitaxel.

Paclitaxel-loaded lipid nanocapsules (PX-LNC) exhibit interesting in vitro characteristics with improved antitumoral activity compared with free PX formulation. Biodistribution studies were realized with the use of (14)C-trimyristin ((14)C-TM) or (14)C-phosphatidylcholine ((14)C-PC) whereas antitumoral activity of PX-LNC formulations was based on the animal survival in a chemically induced hepatocellular carcinoma (HCC) model in Wistar rats. Blood concentration-time profiles for both labeled (14)C-TM-LNC and (14)C-PC-LNC were similar; the t(1/2) and MRT values (over 2h and close to 3h, respectively, for both formulations) indicated the long circulating properties of the LNC carrier with a slow distribution and elimination phase. Survival curves of paclitaxel treated groups showed a statistical significant difference compared to the control survival curve (P=0.0036 and 0.0408). Animals treated with 4x 70 mg/m(2) of PX-LNC showed the most significant increase in mean survival times compared to the controls (IST(mean) 72%) and cases of long-term survivors were preferentially observed in the PX-LNC treated group (37.5%; 3/8). These results demonstrate the great interest to use LNC as drug delivery system for paclitaxel, permitting with an equivalent therapeutic efficiency to avoid the use of excipients such as polyoxyethylated castor oil for its formulation.

T(3;14)(p14.1;q32) involving IGH and FOXP1 is a novel recurrent chromosomal aberration in MALT lymphoma.

The three chromosomal translocations t(11;18)(q21;q21), t(14;18)(q32;q21), and t(1;14)(p22;q32) are associated with MALT lymphoma. In a case of MALT lymphoma of the thyroid, we observed t(3;14)(p14.1;q32) by cytogenetic analysis. Fluorescence in situ hybridization studies showed that the immunoglobulin heavy chain locus (IGH) was rearranged on chromosome 14. Long-distance inverse polymerase chain reaction identified FOXP1 as the partner gene on chromosome 3. To determine the frequency of the t(3;14)(p14.1;q32), two fluorescence in situ hybridization assays were established to screen 91 MALT lymphomas, all of which were negative for the above-mentioned three translocations, and eight splenic and six nodal marginal zone lymphomas. Overall, nine MALT lymphomas (10%) harbored t(3;14)(p14.1;q32) comprising tumors of the thyroid (three of six), ocular adnexa (four of 20), and skin (two of 20), whereas those of the stomach (n = 20), salivary gland (n = 20), and lung (n = 5) were negative as well as the splenic and nodal marginal zone lymphomas. Most t(3;14)(p14.1;q32) + MALT lymphomas harbored additional genetic abnormalities, such as trisomy 3. Further studies revealed that the three known translocations and t(3;14)(p14.1;q32) are mutually exclusive. Real-time quantitative reverse transcriptase polymerase chain reaction showed upregulation of FOXP1 in cases with t(3;14)(p14.1;q32) or trisomy 3. This study identifies FOXP1 as a new translocation partner of IGH in a site-dependent subset of MALT lymphomas.

Variable frequencies of MALT lymphoma-associated genetic aberrations in MALT lymphomas of different sites.

Although several recurrent genetic aberrations are known to occur in MALT lymphoma, no comprehensive study on the most prevalent MALT lymphoma-associated genetic aberrations is available. We therefore screened 252 primary MALT lymphomas for translocations t(11;18)(q21;q21), t(14;18)(q32;q21), and t(1;14)(p22;q32), and trisomies 3 and 18. The above-listed translocations occurred mutually exclusively and were detected overall in 13.5, 10.8, and 1.6% of the cases; trisomy 3 and/or 18 occurred in 42.1%. The frequency at which the translocations occurred varied markedly with the primary site of disease. The t(11;18)(q21;q21) was mainly detected in pulmonary and gastric tumors, whereas the t(14;18)(q32;q21) was most commonly found in lesions of the ocular adnexa/orbit, skin, and salivary glands. Trisomies 3 and 18 each occurred most frequently in intestinal and salivary gland MALT lymphomas. Our results demonstrate that the three translocations and trisomies 3 and 18 occur at markedly variable frequencies in MALT lymphoma of different sites.

Non-degradable microparticles containing a hydrophilic and/or a lipophilic drug: preparation, characterization and drug release modeling.

Non-degradable microparticles based on ammonio methacrylate copolymers (Eudragit RS:RL 4:1 blends) containing the hydrophilic drug propranolol HCl and/or the lipophilic drug nifedipine were prepared with an oil-in-water (O/W) and a water-in-oil-in-water (W/O/W) solvent evaporation technique. Both drugs were successfully incorporated separately as well as simultaneously. In all cases, the resulting release rate(s) of the drug(s) was/were found to be controlled over periods of at least 8 h. To elucidate the underlying mass transport mechanisms, the microparticles were thoroughly characterized by X-ray powder diffractometry, differential scanning calorimetry, particle size analysis, and determination of the actual drug loading(s). Analytical solutions of Fick's second law of diffusion considering non-steady state conditions were used to describe the release of propranolol HCl. Interestingly, the resistance for drug release within the unstirred liquid boundary layers on the surfaces of the microparticles was found to be negligible compared to the diffusional resistance within the polymeric devices. Importantly, the mathematical theories could be used to normalize the experimentally determined in vitro drug release with respect to the microparticle size. Thus, the effect of the type of preparation method (O/W vs. W/O/W) and device composition (polymer blend plus one drug only vs. polymer blend plus drug combination) on the diffusional resistance within the microparticles could be studied. In addition, further insight into the occurring mass transport processes was gained. For example, the time-dependent evolution of the drug concentration profiles within the microparticles upon exposure to the release medium could be calculated. An interesting practical application of the mathematical theories is the possibility to predict the effect of different formulation parameters on the resulting drug release patterns, e.g. the effect of the microparticle size.

Microencapsulation of low molecular weight heparin into polymeric particles designed with biodegradable and nonbiodegradable polycationic polymers.

Owing to its lack of oral absorption, heparin has to be administered parenterally. However, parental administration has negative aspects such as multiple injections, possible infection, patient inconvenience, and high cost. Now, low molecular weight heparin (LMWH) is taking part in antithrombotic treatment and is proven to confer more advantages than unfractionated heparin. The aim of our present study was to formulate, by the w/o/w emulsification process, LMWH microparticles as potential oral carriers prepared with biodegradable (poly-epsilon-caprolactone and poly-lactic-co-glycolic acid) and nonbiodegradable polycationic polymers (Eudragit RS and RL), used alone or blended. The encapsulation efficiency ranged from 16 to 47% and was highly dependent on the presence of the positively charged polymers. In the same way, a low in vitro LMWH release was observed when Eudragit polymers composed totally or partially the polymeric matrix, compared with biodegradable polymers exhibiting higher LMWH release (40 and 60%). For each formulation, LMWH released from microparticles preserved its biological activity as shown by the antifactor Xa activity. Experiments performed with fluorescein-labeled LMWH showed the drug distribution in microparticles and may give information about the mechanisms controlling LMWH encapsulation and release.

Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease.

The use of nanoparticles for targeted oral drug delivery to the inflamed gut tissue in inflammatory bowel disease was examined. Such a strategy of local drug delivery would be a distinct improvement compared with existing colon delivery devices for this disease. An experimental colitis was induced by trinitrobenzenesulfonic acid to male Wistar rats. Rolipram, an anti-inflammatory model drug, was incorporated within poly(lactic-coglycolic acid) nanoparticles, which were administered once a day orally for five consecutive days. A clinical activity score and myeloperoxidase activity were determined to assess the inflammation, whereas an adverse effect index reflected the remaining neurotropic effect of rolipram resulting from its systemic absorption. All nanoparticle formulations proved to be as efficient as the drug in solution in mitigating the experimental colitis. The clinical activity score and myeloperoxidase activity decreased significantly after the oral administration of rolipram nanoparticles or solution. During the next 5 days when animals were kept without drug treatment the drug solution group displayed a strong relapse, whereas the nanoparticle groups continued to show reduced inflammation levels. The rolipram solution group had a high adverse effect index, whereas the rolipram nanoparticle groups proved their potential to retain the drug from systemic absorption as evidenced by a significantly reduced index. This new delivery system enabled the drug to accumulate in the inflamed tissue with higher efficiency than when given as solution. The nanoparticle deposition in the inflamed tissue should be given particular consideration in the design of new carrier systems for the treatment of inflammatory bowel disease.

Size-dependent bioadhesion of micro- and nanoparticulate carriers to the inflamed colonic mucosa.

PURPOSE: The size-dependent deposition of microparticles and nanoparticles after oral administration to rats using an experimental model colitis was examined. Local delivery of an entrapped drug could reduce side effects and would be a distinct improvement compared with existing colon delivery devices. METHODS: Ulcerative colitis was induced in Lewis rats with trinitrobenzenesulfonic acid. Fluorescent polystyrene particles with a size of 0.1, 1, or 10 microm were administered for 3 days. The animals then were sacrificed and their guts resected. Particle distribution in the colon was imaged by confocal laser scanning microscopy and quantified by fluorescence spectrophotometry. RESULTS: In the inflamed tissue, an increased adherence of particles was observed at the thicker mucus layer and in the ulcerated regions. A size dependency of the deposition was found, and an increased number of attached particles to the colon was determined compared with the control group. For 10-micorm particles, only fair deposition was observed (control group: 1.4 +/- 0.6%; colitis: 5.2 +/- 3.8% of administered particle mass). One-micrometer particles showed higher binding (control group: 2.0 +/- 0.8%; colitis: 9.1 +/- 4.2%). Highest binding was found for 0.1-microm particles (control group: 2.2 +/- 1.6%; colitis: 14.5 +/- 6.3%). The ratio of colitis/control deposition increased with smaller particle sizes. CONCLUSIONS: The use of submicron-sized carriers holds promise for the targeted delivery of drugs to the inflamed colonic mucosal areas in inflammatory bowel disease.

Influences of process parameters on preparation of microparticle used as a carrier system for omega - 3 unsaturated fatty acid ethyl esters used in supplementary nutrition.

Microparticles were prepared by complex coacervation to encapsulate eicosapentaenoic acid ethyl ester (EPA-EE) for incorporation into foods as a nutrition supplement. Gelatin and acacia were used in the coacervation process. With an increasing oil/polymer ratio, both yield and encapsulation rate decreased; with an increasing homogenization time, the yield remained constant while the encapsulation rate slightly increased. Several particle hardening techniques were examined and their influence on particle structure, yield and encapsulation rate were examined. Ethanol hardening was compared to cross-linking with dehydroascrobic acid with respect to both yield and encapsulation rate. The particle diameters for both formulations were similar (ethanol: 38.4 +/- 4.1 microm; cross-linking: 41.8 +/- 3.0 microm). Spray-drying of the coacervates led to the smallest particles (5.2 +/- 1.1 microm), lowest yield and encapsulation rate. All microencapsulation products were assayed for their storage stability over 4 weeks with respect to the oxidation of the encapsulated omega - 3 unsaturated fatty acid ester inside the particles. Hardening with ethanol showed the lowest amount of peroxides: particle wall cross-linking by dehydroascorbic acid and spray-drying were observed to be less protective. All microparticles were characterized for their internal structure with confocal laser scanning microscopy (CLSM) after fluorescence labelling of the polymers, in order to localize the oil phase and visualize the distribution of the polymers in the coacervates. With increasing homogenization time, the internal structure changed stepwise from a capsule structure (core/wall) towards a matrix structure. For all experiments, a homogeneous distribution for both polymers, gelatin and acacia was observed inside the particle wall. No influence of the different particle hardening procedures on the polymer distribution was found.

Design of rolipram-loaded nanoparticles: comparison of two preparation methods.

The aim of the present work was to investigate the preparation of nanoparticles as a potential drug carrier and targeting system for the treatment of inflammatory bowel disease. Rolipram was chosen as the model drug to be incorporated within nanoparticles. Pressure homogenization-emulsification (PHE) with a microfluidizer or a modified spontaneous emulsification solvent diffusion method (SESD) were used in order to select the most appropriate preparation method. Poly(epsilon-caprolactone) has been used for all preparations. The drug loading has been optimized by varying the concentration of the drug and polymer in the organic phase, the surfactants (polyvinyl alcohol, sodium cholate) as well as the volume of the external aqueous phase. The rolipram encapsulation efficiency was high (>85%) with the PHE method in all cases, whereas with the SESD method encapsulation efficiencies were lower (<40%) when lower surfactant concentrations and reduced volume of aqueous phase were used. Release profiles were characterized by a substantial initial burst release with the PHE method (25-35%) as well as with the SESD method (70-90%). A more controlled release was obtained after 2 days of dissolution with the PHE method (70-90%), no further significant drug release was observed with the SESD method.

Study of beta-lactoglobulin/acacia gum complex coacervation by diffusing-wave spectroscopy and confocal scanning laser microscopy.

Complex coacervation has been investigated on mixtures of beta-lactoglobulin (beta-lg) and acacia gum (AG) at pH 4.2 where these two macromolecules interact electrostatically. Changes in beta-lg/AG complex coacervation induced by the presence of beta-lg aggregates were considered. The nature and structure of particles resulting from complex coacervation were determined by using confocal scanning laser microscopy (CSLM). CSLM revealed fundamental differences in the structure of each of the studied dispersions (at 1 wt.% total concentration). Spherical vesicular coacervates and precipitates (based on beta-lg aggregates) were the hallmark of BLG/AG dispersions (beta-lg dispersion containing insoluble aggregates). Only coacervates were visible in AF-BLG/AG dispersions (beta-lg dispersion free of insoluble aggregates). The latter were characterised by the presence of large foam-like coacervates induced by partial coalescence of single coacervates, especially at the 2:1 protein to polysaccharide (Pr:Ps) ratio. Diffusing wave spectroscopy (DWS) was used to study the stability of dispersions as a function of time. Depending on the Pr:Ps ratio and the presence of beta-lg aggregates, the intensity correlation function (g(2)(t)) shifted to lower correlation times rapidly after mixing of both macromolecules. This revealed the formation of a large number of small particles, characterised by faster Brownian motion. At 1 and 5 wt.% total concentration, the 8:1 Pr:Ps ratio exhibited a rapid decrease of the backscattered intensity in time, both for BLG/AG and AF-BLG/AG mixtures, revealing rapid sedimentation/coalescence of particles. This precluded the achievement of a stable correlation function. For the 2:1 Pr:Ps ratio, mixtures exhibited both coalescence and sedimentation phenomena as confirmed by shifts in the g(2)(t) towards larger correlation times and the decrease of the initial value of g(2)(t) with time. Mixtures obtained for the 1:1 Pr:Ps ratio were characterised by small variations in the DWS signal, emphasising the stability of produced particles. The increase of the total biopolymer concentration reduced the effect of both Pr:Ps ratio and presence of protein aggregates. From CSLM and DWS observations, possible differences in the complex coacervation mechanism in both types of mixtures were highlighted. The use of protein aggregates to control complex coacervation was underlined.

Biodegradable microparticles as a two-drug controlled release formulation: a potential treatment of inflammatory bowel disease.

A multiple unit dosage form for oral delivery based on the microencapsulation of anti-inflammatory drugs using different biodegradable polymers, poly(epsilon-caprolactone), polylactic acid and poly(lactic-co-glycolic acid), prepared either by the water-in-oil-in-water (w/o/w) or the solid-in-oil-in-water (s/o/w) solvent evaporation method was developed. Microparticles were characterized for their size, morphology, encapsulation efficiency and drug release. The physical state of drugs and polymers was determined by differential scanning calorimetry (DSC), imaging of the particles was performed by scanning electron microscopy and confocal laser scanning microscopy. Sulfasalazine and betamethasone used for the treatment of inflammatory bowel disease, were chosen as model drugs. The microparticles were spherical with diameters in the range of 91 to 258 microm by the w/o/w-method, and in the range of 102 to 277 microm by the s/o/w-method. The encapsulation efficiency (EE) varied between 11 and 16% for sulfasalazine and 50 and 67% for betamethasone with the w/o/w-method, and between 73 and 79% for sulfasalazine and 60 and 70% for betamethasone with the s/o/w-method. DSC showed no interaction between polymers and drugs, while the drugs were dispersed in the polymer. In vitro release studies showed a controlled release of sulfasalazine and betamethasone from microparticles prepared by the s/o/w-method; a pronounced burst release of sulfasalazine was observed from microparticles prepared by the w/o/w-method.

The preparation and evaluation of poly(epsilon-caprolactone) microparticles containing both a lipophilic and a hydrophilic drug.

An original dosage form for oral delivery based on the encapsulation of both, lipophilic and hydrophilic drugs, in poly(epsilon-caprolactone) (PCL) microparticles prepared either by the oil-in-water (o/w) or the water-in-oil-in-water (w/o/w) solvent evaporation method was developed. Microparticles were characterized in terms of morphology, size, encapsulation efficiency and drug release. The physical state of the drugs and the polymer was determined by scanning electron microscopy (SEM), X-ray powder diffractometry, and differential scanning calorimetry (DSC). Nifedipine (calcium antagonist) and propranolol HCl (beta-blocker), used for the treatment of hypertension, were chosen as lipophilic and hydrophilic drugs. The microparticles were spherical with diameters in the range of 191-351 microm by the o/w-method, and in the range of 302-477 microm by the w/o/w-method. The encapsulation efficiency (EE) was 91% for nifedipine and 37% for propranolol HCl with the o/w-method, and 83% for nifedipine and 57% for propranolol HCl with the w/o/w-method. DSC and X-ray diffraction studies showed that PCL maintained its semi-crystalline structure, while the drugs were either dispersed or dissolved in the polymer. In vitro release studies revealed a controlled release of nifedipine and propranolol HCl from microparticles prepared by the o/w-method; a burst release of propranolol HCl was observed from microparticles prepared by the w/o/w-method. In conclusion, microparticles containing both a hydrophilic and a lipophilic drug were successfully prepared.

Influences of process parameters on nanoparticle preparation performed by a double emulsion pressure homogenization technique.

The preparation of nanoparticles (NP) as an improved colloidal carrier system for proteins was investigated. Bovine serum albumin (BSA) was used as model drug. Owing to the high solubility of the protein in water, the double emulsion technique has been chosen as one of the most appropriate method. In order to both reaching submicron size as well as increasing the grade of monodispersity compared to previous preparation techniques, a microfluidizer as homogenization device was used. All experiments were performed using two biodegradable polymers, poly[D,L-lactic-co-glycolic acid] 50/50 (PLGA) and poly[epsilon-caprolactone] (PCL). The homogenization procedure has been optimized with regard to particle size and monodispersity by studying the influence of the homogenization time as well as the amount of polymer and surfactant in the external aqueous phase. The drug loading has been improved by varying the concentration of the protein in the inner aqueous phase. By increasing the protein concentration in the inner aqueous phase the polydispersity was slightly higher, while the particle size was not influenced significantly. The BSA encapsulation efficiency decreased with higher protein concentration in the inner aqueous phase. All release profiles were characterized by a initial burst effect, a higher release rate was obtained after 4 weeks for PLGA NP (60%) compared with PCL NP (47%).