Oral and dermal toxicity of alkenones extracted from Isochrysis species

Author Posting. © Bioscience Research Institute, 2020. This article is posted here by permission of Bioscience Research Institute for personal use, not for redistribution. The definitive version was published in McIntosh, K., Sarver, J., Mell, K., Terrero, D. J., Ashby, C. R., Reddy, C., O’Neil, G., Ramapuram, J. B., & Tiwari, A. K. Oral and dermal toxicity of alkenones extracted from Isochrysis species. Frontiers in Bioscience-Landmark, 25(5), (2020): 817–837, https://doi.org/10.2741/4836.Isochrysis is commercially available marine algae used for animal feed, human nutrient supplements, and biodiesel. The Isochrysis species is one of five genera of haptophytes that produces unique, long-chain lipids known as alkenones that are promising new ingredients for green cosmetics, personal care products and pharmaceutical delivery. However, there is a lack of toxicity data for alkenones in animals, thus limiting their use in humans. In this study, we performed acute oral, acute dermal, and repeated 28-day dermal toxicity studies, using female SAS Sprague Dawley Rats. Our behavioral studies indicated that the specific alkenones had no overt behavioural effects at oral doses up to 4000 mg/kg. In the acute and chronic dermal toxicity studies, the alkenones produced less irritation and did not significantly damage the skin based on the Draize skin reaction scale and trans-epidermal water loss readings compared to the positive control, 1% sodium lauryl sulfate. Overall, our results indicated that alkenones are safe in Sprague Dawley rats, suggesting that they could be used for both oral and dermal formulations, although additional studies will be required.This work was supported by the Marine Biological Laboratory Woods Hole Oceanographic Institute (WHOI) under grant (N-126665-01, 2017), Washington Research Foundation, and University of Toledo start-up funding under a grant (F110760) to A.K.T. The authors declare no conflict of interest

Development of a sustained-release voriconazole-containing thermogel for subconjunctival injection in horses

PURPOSE. To determine in vitro release profiles, transcorneal permeation, and ocular injection characteristics of a voriconazole-containing thermogel suitable for injection into the subconjunctival space (SCS). METHODS. In vitro release rate of voriconazole (0.3% and 1.5%) from poly (DL-lactide-coglycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) thermogel was determined for 28 days. A Franz cell diffusion chamber was used to evaluate equine transcorneal and transscleral permeation of voriconazole (1.5% topical solution, 0.3% and 1.5% voriconazole-thermogel) for 24 hours. Antifungal activity of voriconazole released from the 1.5% voriconazole-thermogel was determined via the agar disk diffusion method. Ex vivo equine eyes were injected with liquid voriconazole-thermogel (4°C). Distension of the SCS was assessed ultrasonographically and macroscopically. SCS voriconazole-thermogel injections were performed in a horse 1 week and 2 hours before euthanasia and histopathologic analysis of ocular tissues performed. RESULTS. Voriconazole was released from the PLGA-PEG-PLGA thermogel for more than 21 days in all groups. Release followed first-order kinetics. Voriconazole diffused through the cornea and sclera in all groups. Permeation was greater through the sclerae than corneas. Voriconazole released from the 1.5% voriconazole-thermogel showed antifungal activity in vitro. Voriconazole-thermogel was easily able to be injected into the dorsal SCS where it formed a discrete gel deposit. Voriconazole-thermogel was easily injected in vivo and did not induce any adverse reactions. CONCLUSIONS. Voriconazole-containing thermogels have potential application in treatment of keratomycosis. Further research is required to evaluate their performance in vivo

Influence of Stefan blowing on nanofluid flow submerged in microorganisms with leading edge accretion or ablation

The unsteady forced convective boundary layer flow of viscous incompressible fluid containing both nanoparticles and gyrotactic microorganisms, from a flat surface with leading edge accretion (or ablation), is investigated theoretically. Utilizing appropriate similarity transformations for the velocity, temperature, nanoparticle volume fraction and motile microorganism density, the governing conservation equations are rendered into a system of coupled, nonlinear, similarity ordinary differential equations. These equations, subjected to imposed boundary conditions, are solved numerically using the Runge-Kutta-Fehlberg fourth-fifth order numerical method in the MAPLE symbolic software. Good agreement between our computations and previous solutions is achieved. The effect of selected parameters on flow velocity, temperature, nano-particle volume fraction (concentration) and motile microorganism density function is investigated. Furthermore, tabular solutions are included for skin friction, wall heat transfer rate, nano-particle mass transfer rate and microorganism transfer rate. Applications of the study arise in advanced micro-flow devices to assess nanoparticle toxicity

Notes for genera: basal clades of Fungi (including Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota)

Compared to the higher fungi (Dikarya), taxonomic and evolutionary studies on the basal clades of fungi are fewer in number. Thus, the generic boundaries and higher ranks in the basal clades of fungi are poorly known. Recent DNA based taxonomic studies have provided reliable and accurate information. It is therefore necessary to compile all available information since basal clades genera lack updated checklists or outlines. Recently, Tedersoo et al. (MycoKeys 13:1--20, 2016) accepted Aphelidiomycota and Rozellomycota in Fungal clade. Thus, we regard both these phyla as members in Kingdom Fungi. We accept 16 phyla in basal clades viz. Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota. Thus, 611 genera in 153 families, 43 orders and 18 classes are provided with details of classification, synonyms, life modes, distribution, recent literature and genomic data. Moreover, Catenariaceae Couch is proposed to be conserved, Cladochytriales Mozl.-Standr. is emended and the family Nephridiophagaceae is introduced

Glass transitions in binary drug + polymer systems

To evaluate miscibility, glass transition temperatures Tg have been determined for two binary polymer (Plasdone S-630 copovidone or Eudragit® E) + drug systems as a function of composition. Each polymer serves for encapsulation of the anti-HIV drug Efavirenz. In both systems the Tg vs. drug concentration diagrams are s-shaped. Tgs of Efavirenz + Plasdone mixtures with drug mass fraction below φdrug = 0.6 are above linear values. This implies enhanced thermal and mechanical stability-an advantage for the drug encapsulation. In the other system, a strong negative deviation of Tgs is observed over the entire compositional range and explained by positive excess mixing volumes. Several equations are used to represent Tg vs. composition diagrams, but only one (Brostow et al. Mater Lett 2008; 62:3152) provides reliable results. © 2009 Elsevier B.V. All rights reserved

Clinical outcomes of chemotherapy in cancer patients with different ethnicities

Abstract Background Choosing the most effective chemotherapeutic agent with safest side effect profile is a common challenge in cancer treatment. Although there are standardized chemotherapy protocols in place, protocol changes made after extensive clinical trials demonstrate significant improvement in the efficacy and tolerability of certain drugs. The pharmacokinetics, pharmacodynamics, and tolerance of anti‐cancer medications are all highly individualized. A driving force behind these differences lies within a person's genetic makeup. Recent findings Pharmacogenomics, the study of how an individual's genes impact the processing and action of a drug, can optimize drug responsiveness and reduce toxicities by creating a customized medication regimen. However, these differences are rarely considered in the initial determination of standardized chemotherapeutic protocols and treatment algorithms. Because pharmacoethnicity is influenced by both genetic and nongenetic variables, clinical data highlighting disparities in the frequency of polymorphisms between different ethnicities is steadily growing.  Recent data suggests that ethnic variations in the expression of allelic variants may result in different pharmacokinetic properties of the anti‐cancer medication. In this article, the clinical outcomes of various chemotherapy classes in patients of different ethnicities were reviewed. Conclusion Genetic and nongenetic variables contribute to the interindividual variability in response to chemotherapeutic drugs. Considering pharmacoethnicity in the initial determination of standard chemotherapeutic protocols and treatment algorithms can lead to better clinical outcomes of patients of different ethnicities

pH-Sensitive Liposomes for Enhanced Cellular Uptake and Cytotoxicity of Daunorubicin in Melanoma (B16-BL6) Cell Lines

Daunorubicin (DNR) was delivered using a pH-sensitive liposomal system in B16-BL6 melanoma cell lines for enhanced cytotoxic effects. DNR was encapsulated within liposomes and CL as a component of the lipid bilayer. PEGylated pH-sensitive liposomes, containing CL, were prepared in the molar ratio of 40:30:5:17:8 for DOPE/cholesterol/DSPE-mPEG (2000)/CL/SA using the lipid film hydration method and loaded with DNR (drug: lipid ratio of 1:5). The CL liposomes exhibited high drug encapsulation efficiency (>90%), a small size (~94 nm), narrow size distribution (polydispersity index ~0.16), and a rapid release profile at acidic pH (within 1 h). Furthermore, the CL liposomes exhibited 12.5- and 2.5-fold higher cytotoxicity compared to DNR or liposomes similar to DaunoXome®. This study provides a basis for developing DNR pH-sensitive liposomes for melanoma treatment

Photodynamic therapy: A special emphasis on nanocarrier-mediated delivery of photosensitizers in antimicrobial therapy

Resistance to antimicrobial drugs is an impending healthcare problem of growing significance. In the post-antibiotic era, there is a huge push to develop new tools for effectively treating bacterial infections. Photodynamic therapy involves the use of a photosensitizer that is activated by the use of light of an appropriate wavelength in the presence of oxygen. This results in the generation of singlet oxygen molecules that can kill the target cells, including cancerous cells and microbial cells. Photodynamic therapy is shown to be effective against parasites, viruses, algae, and bacteria. To achieve high antimicrobial activity, a sufficient concentration of photosensitizer should enter the microbial cells. Generally, photosensitizers tend to aggregate in aqueous environments resulting in the weakening of photochemical activity and lowering their uptake into cells. Nanocarrier systems are shown to be efficient in targeting photosensitizers into microbial cells and improve their therapeutic efficiency by enhancing the internalization of photosensitizers into microbial cells. This review aims to highlight the basic principles of photodynamic therapy with a special emphasis on the use of nanosystems in delivering photosensitizers for improving antimicrobial photodynamic therapy