Toxoplasmic encephalitis (TE) is the most common clinical manifestation of reactivated infection with Toxoplasma gondii in immunocompromised patients that is lethal if untreated. The combination of pyrimethamine plus sulfadiazine or clindamycin is the standard therapy for the treatment of TE, but these combinations are associated with hematologic toxicity and/or life-threatening allergic reactions. Therefore, alternative treatment options are needed. Atovaquone is safe and highly effective against T. gondii in vitro, but the oral micronized solution shows poor bioavailability. We synthesized atovaquone nanosuspensions (ANSs) coated with poloxamer 188 (P188) and sodium dodecyl sulfate (SDS) to improve oral bioavailability and passage through the blood-brain barrier (BBB). Coating of ANSs with SDS resulted in enhanced oral bioavailability and enhanced brain uptake of atovaquone compared to Wellvone(®) in murine models of acute and reactivated toxoplasmosis as measured by high performance liquid chromatography (HPLC). Parasite loads and inflammatory changes in brains of mice treated with SDS-coated ANS were significantly reduced compared to untreated controls and to Wellvone(®)-treated mice. In conclusion, nanosuspensions coated with SDS may ultimately lead to improvements in the treatment of TE and other cerebral diseases.

Single-case, longitudinal studies of the three-dimensional vestibulo-ocular response (VOR) were conducted with two spaceflight subjects over a 180-day mission. For reference, a control study was performed in the laboratory with 13 healthy volunteers. Horizontal, vertical and torsional VOR was measured during active yaw, pitch and roll oscillations of the head, performed during visual fixation of real and imaginary targets. The control group was tested in the head-upright position, and in the gravity-neutral, onside and supine positions. Binocular eye movements were recorded throughout using videooculography, yielding eye position in Fick co-ordinates. Eye velocity was calculated using quaternion algebra. Head angular velocities were measured by a head-mounted rate sensor. Eye/head velocity gain and phase were evaluated for the horizontal, vertical and torsional VOR. The inclination of Listing's plane was also calculated for each test session. Control group gain for horizontal and vertical VOR was distributed closely around unity during real-target fixation, and reduced by 30-50% during imaginary-target trials. Phase was near zero throughout. During head pitch in the onside position, vertical VOR gain did not change significantly. Analysis of up/down asymmetry indicated that vertical VOR gain for downward head movement was significantly higher than for upward head movement. Average torsional VOR gain with real-target fixation was significantly higher than with imaginary-target fixation. No difference in phase was found. In contrast to vertical VOR gain, torsional VOR gain was significantly lower in the gravity-neutral supine position. Spaceflight subjects showed no notable modification of horizontal or vertical VOR gain or phase during real-target fixation over the course of the mission. However, the up/down asymmetry of vertical VOR gain was inverted in microgravity. Torsional VOR gain was clearly reduced in microgravity, with some recovery in the later phase. After landing, there was a dip in gain during the first 24 h, with subsequent recovery to near baseline over the 13-day period tested. Listing's plane appeared to remain stable throughout the mission. The findings reflect various functions of the otolith responses. The reduced torsional VOR gain in microgravity is attributed to the absence of the gravity-dependent, dynamic stimulation to the otoliths (primarily utricles). On the other hand, the reversal of vertical VOR up/down gain asymmetry in microgravity is attributed to the off-loading of the constant 1-g bias (primarily to the saccules) on Earth. The observed increase in torsional VOR gain from the 1st to the 6th month in microgravity demonstrates the existence of longer-term adaptive processes than have previously been considered. Likely factors are the adaptive reweighting of neck-proprioceptive afferents and/or enhancement of efference copy.

Increasing number of antiretroviral drugs coming from high throughput screening besides their high dose has poor solubility profile. Formulation development of these drugs is a major obstacle to their clinical application. To overcome extremely low water solubility and associated poor bioavailability they can be formulated as nanosuspensions. This paper is not only focuses on production of parenteral nevirapine nanosuspensions but also on scaling up of formulations for clinical use. Lab scale (APV LAB 40, 40 mL) and medium scale (Avestin C50, 2 kg) production was performed using piston gap high pressure homogenization (HPH), while the feasibility for pilot scale up was checked using a bead milling technique in continuous mode (PM, Bühler PML-2). Nanosuspension was characterized for particle sizes, zeta potential, crystallanity and stability. The mean particle sizes for lab scale, medium scale and pilot scale production obtained were 481 nm, 429 nm and 211 nm, respectively. Independent of the production method (lab and pilot scale) all processed formulations showed more or less similar zeta potential (~15 mV) in conductivity adjusted water. Long term stability over 1 year showed significant increase in particle size at all storage conditions for lab scale and medium scale production (high energy size reduction) whereas they remained physically stable (with negligible increase) for the milled product (low energy size reduction). As the technology has been scaled up successfully for nevirapine nanosuspension, the product can be considered for commercial exploitation. The prepared nevirapine nanosuspensions can be administered for parenteral or oral use.

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For many biomedical applications, material surfaces should not only prevent unspecific protein adsorption and bacterial attachment as in many other applications in the food, health, or marine industry, but they should also promote the adhesion of tissue cells. In order to take a first step toward the challenging development of protein and bacteria-repelling and cell-adhesion-promoting materials, polyamine and poly­(amido amine) surface coatings with terminal amine groups and varying structure (dendrimer, oligomer, polymer) were immobilized on model surfaces via silane chemistry. Physicochemical analysis showed that all modifications are hydrophilic (contact angles <60°) and possess similar surface free energies (SFEs, ∼46–54 mN/m), whereas their amine group densities and zeta potentials at physiological conditions (pH 7.4) varied greatly (−50 to +75 mV). In protein adsorption experiments with single proteins (human serum albumin (HSA) and lysozyme) as well as complex physiological fluids (fetal bovine serum (FBS) and human saliva), the amounts of adsorbed protein were found to correlate strongly with the zeta potential of the surface coatings. Both modifications based on linear polymers exhibited good protein repellency toward all proteins examined and are thus promising for testing in cell adhesion studies.