Efficiency of a dexamethasone nanosuspension as an intratympanic injection for acute hearing loss.

Dexamethasone sodium phosphate (Dex-SP) is the most commonly used drug administered via intratympanic injection for the treatment of acute hearing loss, but its penetration efficiency into the inner ear is very low. To address this problem, we evaluated the possibility of administering dexamethasone nanosuspensions via intratympanic injection because hydrophobic drugs might be more effective in penetrating the inner ear. Three types of dexamethasone nanosuspensions were prepared; the dexamethasone nanoparticles in the three nanosuspensions were between approximately 250 and 350 nm in size. To compare the efficiency of Dex-SP and dexamethasone nanosuspension in delivering dexamethasone to the inner ear, the concentrations of dexamethasone in perilymph and cochlear tissues were compared by liquid chromatography-mass spectrometry. The dexamethasone nanosuspensions resulted in significantly higher drug concentrations in perilymph and cochlear tissues than Dex-SP at 6 h; interestingly, animals treated with nanosuspensions showed a 26-fold higher dexamethasone concentrations in their cochlear tissues than animals treated with Dex-SP. In addition, dexamethasone nanosuspension caused better glucocorticoid receptor phosphorylation than Dex-SP both in vitro and in vivo, and in the ototoxic animal model, the nanosuspension showed a significantly better hearing-protective effect against ototoxic drugs than Dex-SP. In the in vivo safety evaluation, the nanosuspension showed no toxicity at concentrations up to 20 mg/mL. In conclusion, a nanosuspension of dexamethasone was able to deliver dexamethasone to the cochlea very safely and efficiently and showed potential as a formula for intratympanic injection.

Development of sorafenib loaded nanoparticles to improve oral bioavailability using a quality by design approach.

Sorafenib, a potent anticancer drug, has low absorption in the gastrointestinal tract due to its poor aqueous solubility. The main purpose of this investigation was to design sorafenib nanoparticle using a newly developed technique, nanoparticulation using fat and supercritical fluid (NUFS™) to improve the absorption of sorafenib. The quality by design (QbD) tool was adopted to define the optimal formulation variables: hydroxypropyl methyl cellulose (HPMC), polyvinyl pyrrolidone K30 (PVP), and poloxamer. The studied response variables were particle size of nanoparticle, dissolution (5, 60, and 180 min), drug concentration time profile of nanoparticle formulations, and maximum drug concentration. The result of particle size revealed that an increase in concentration of poloxamer and HPMC decreased the particle size of nanoparticles (p < 0.05). Likewise, the concentration of drug release at different time point (5, 60, and 180 min) showed HPMC and poloxamer had positive effects on drug dissolution while PVP had negative effects on it. The design space was built in accordance with the particle size of nanoparticle (target < 500 nm) and dissolution of sorafenib (target > 7 µm/mL), following failure probability analysis using Monte Carlo simulations. In vivo pharmacokinetics studies in beagle dogs demonstrated that optimized formulation of sorafenib (F3 and F4 tablets) exhibited higher blood drug profiles indicating better absorption compared to the reference tablet (Nexavar®). In conclusion, this study showed the importance of systematic formulation design for understanding the effect of formulation variables on the characteristics of nanoparticles of the poorly soluble drug.

Influence of Water Depth on Microalgal Production, Biomass Harvest, and Energy Consumption in High Rate Algal Pond Using Municipal Wastewater.

The high rate algal ponds (HRAP) powered and mixed by a paddlewheel have been widely used for over 50 years to culture microalgae for the production of various products. Since light incidence is limited to the surface, water depth can affect microalgal growth in HRAP. To investigate the effect of water depth on microalgal growth, a mixed microalgal culture constituting three major strains of microalgae including Chlorella sp., Scenedesmus sp., and Stigeoclonium sp. (CSS), was grown at different water depths (20, 30, and 40 cm) in the HRAP, respectively. The HRAP with 20cm of water depth had about 38% higher biomass productivity per unit area (6.16 ± 0.33 g·m⁻²·d⁻¹) and required lower nutrients and energy consumption than the other water depths. Specifically, the algal biomass of HRAP under 20c m of water depth had higher settleability through larger floc size (83.6% settleability within 5 min). These results indicate that water depth can affect the harvesting process as well as cultivation of microalgae. Therefore, we conclude that water depth is an important parameter in HRAP design for mass cultivation of microalgae.

Microalgal diversity fosters stable biomass productivity in open ponds treating wastewater.

It is established that biodiversity determines productivity of natural ecosystems globally. We have proved that abiotic factors influenced biomass productivity in engineered ecosystems i.e. high rate algal ponds (HRAPs), previously. This study demonstrates that biotic factors, particularly microalgal diversity, play an essential role in maintaining stable biomass productivity in HRAP treating municipal wastewater by mutualistic adaptation to environmental factors. The current study examined data from the second year of a two-year study on HRAP treating municipal wastewater. Microalgal diversity, wastewater characteristics, treatment efficiency and several environmental and meteorological factors were documented. Multivariate statistical analyses reveal that microalgae in uncontrolled HRAPs adapt to adverse environmental conditions by fostering diversity. Subsequently, five dominant microalgal strains by biovolume were isolated, enriched, and optimum conditions for high biomass productivity were ascertained. These laboratory experiments revealed that different microalgal strains dominate in different conditions and a consortium of these diverse taxa help in sustaining the algae community from environmental and predatory pressures. Diversity, niche or seasonal partitioning and mutualistic growth are pertinent in microalgal cultivation or wastewater treatment. Therefore, enrichment of selective species would deprive the collective adaptive ability of the consortium and encourage system vulnerability especially in wastewater treatment.

Polypropylene Bundle Attached Multilayered Stigeoclonium Biofilms Cultivated in Untreated Sewage Generate High Biomass and Lipid Productivity.

The potential of microalgae biofuel has not been realized because of the low productivity and high costs associated with the current cultivation systems. In this study, a new low-cost and transparent attachment material was tested for cultivation of a filamentous algal strain, Stigeoclonium sp., isolated from wastewater. Initially, the different materials tested for Stigeoclonium cultivation in untreated wastewater were nylon mesh, polyethylene mesh, polypropylene bundle (PB), polycarbonate plate, and viscose rayon. Among the materials tested, PB led to a firm attachment, high biomass (53.22 g/m(2), dry cell weight), and total lipid yield (5.8 g/m(2)) with no perceivable change in FAME profile. The Stigeoclonium-dominated biofilm consisted of bacteria and extracellular polysaccharide, which helped in biofilm formation and for effective wastewater treatment (viz., removal efficiency of total nitrogen and total phosphorus corresponded to ~38% and ~90%, respectively). PB also demonstrated high yields under multilayered cultivation in a single reactor treating wastewater. Hence, this system has several advantages over traditional suspended and attached systems, with possibility of increasing areal productivity three times using Stigeoclonium sp. Therefore, multilayered attached growth algal cultivation systems seem to be the future cultivation model for large-scale biodiesel production and wastewater treatment.

Organic carbon, influent microbial diversity and temperature strongly influence algal diversity and biomass in raceway ponds treating raw municipal wastewater.

Algae based wastewater treatment coupled to biofuel production has financial benefits and practical difficulties. This study evaluated the factors influencing diversity and growth of indigenous algal consortium cultivated on untreated municipal wastewater in a high rate algal pond (HRAP) for a period of 1 year using multivariate statistics. Diversity analyses revealed the presence of Chlorophyta, Cyanophyta and Bacillariophyta. Dominant microalgal genera by biovolume in various seasons were Scenedesmus sp., Microcystis sp., and Chlorella sp. Scenedesmus sp., persisted throughout the year but none of three strains co-dominated with the other. The most significant factors affecting genus dominance were temperature, inflow cyanophyta and organic carbon concentration. Cyanophyta concentration affected microalgal biomass and diversity, whereas temperature impacted biomass. Preferred diversity of microalgae is not sustained in wastewater systems but is obligatory for biofuel production. This study serves as a guideline to sustain desired microalgal consortium in wastewater treatment plants for biofuel production.

A cost analysis of microalgal biomass and biodiesel production in open raceways treating municipal wastewater and under optimum light wavelength.

Open raceway ponds are cost-efficient for mass cultivation of microalgae compared with photobioreactors. Although low-cost options like wastewater as nutrient source is studied to overcome the commercialization threshold for biodiesel production from microalgae, a cost analysis on the use of wastewater and other incremental increases in productivity has not been elucidated. We determined the effect of using wastewater and wavelength filters on microalgal productivity. Experimental results were then fitted into a model, and cost analysis was performed in comparison with control raceways. Three different microalgal strains, Chlorella vulgaris AG10032, Chlorella sp. JK2, and Scenedesmus sp. JK10, were tested for nutrient removal under different light wavelengths (blue, green, red, and white) using filters in batch cultivation. Blue wavelength showed an average of 27% higher nutrient removal and at least 42% higher chemical oxygen demand removal compared with white light. Naturally, the specific growth rate of microalgae cultivated under blue wavelength was on average 10.8% higher than white wavelength. Similarly, lipid productivity was highest in blue wavelength, at least 46.8% higher than white wavelength, whereas FAME composition revealed a mild increase in oleic and palmitic acid levels. Cost analysis reveals that raceways treating wastewater and using monochromatic wavelength would decrease costs from 2.71 to 0.73 $/kg biomass. We prove that increasing both biomass and lipid productivity is possible through cost-effective approaches, thereby accelerating the commercialization of low-value products from microalgae, like biodiesel.

Nutrient removal and biofuel production in high rate algal pond using real municipal wastewater.

This study evaluated the growth and nutrient removal ability of an indigenous algal consortium on real untreated municipal wastewater in a high rate algal pond (HRAP). The HRAP was operated semicontinuously under different hydraulic retention times (HRT: 2, 4, 6, and 8 days). The average removal efficiencies of chemical oxygen demand, and total nitrogen and phosphate of real municipal wastewater were maintained at 85.44 ± 5.10%, 92.74 ± 5.82%, and 82.85 ± 8.63%, respectively, in 2 day HRT. Algae dominated the consortium and showed high settling efficiency (99%), and biomass and lipid productivity of 0.500 ± 0.03 g/l/day and 0.103 ± 0.0083 g/l/day (2 day HRT), respectively. Fatty acid methyl ester analysis revealed a predominance of palmitate (C16:0), palmitoleate (C16:1), linoleate (C18:2), and linolenate (C18:3). Microalgal diversity analyses determined the presence of Chlorella, Scenedesmus, and Stigeoclonium as the dominant microalgae. The algal consortium provides significant value not only in terms of energy savings and nutrient removal but also because of its bioenergy potential as indicated by the lipid content (20-23%) and FAME profiling.