Development and Characterization of Nanoemulsions for Ophthalmic Applications: Role of Cationic Surfactants

The eye is a very complex organ comprising several physiological and physical barriers that compromise drug absorption into deeper layers. Nanoemulsions are promising delivery systems to be used in ocular drug delivery due to their innumerous advantages, such as high retention time onto the site of application and the modified release profile of loaded drugs, thereby contributing to increasing the bioavailability of drugs for the treatment of eye diseases, in particular those affecting the posterior segment. In this review, we address the main factors that govern the development of a suitable nanoemulsion formulation for eye administration to increase the patient’s compliance to the treatment. Appropriate lipid composition and type of surfactants (with a special emphasis on cationic compounds) are discussed, together with manufacturing techniques and characterization methods that are instrumental for the development of appropriate ophthalmic nanoemulsions.

Elution profile of cationic and anionic adsorbate from exhausted adsorbent using solvent desorption

Present invention involves to study the elution profile of anionic and cationic compounds from exhausted adsorbents using various eluents. Batch elution studies of anionic components like Congo Red dye and Carbonate ion; and cationic compounds such as Methylene blue dye and Cadmium metal from previously used naturally prepared adsorbents i.e. Gulmohar (Delonix regia) leaf powder - GLP; and Neem (Azadirachta indica) leaf powder – NLP and their derivatives were conducted. Different eluents used for batch study were various acids and alkaline solution having various concentration and solvents having different functional groups in seven sorption-desorption cycles. The batch data were accessed by kinetic models (Pseudo First-, Pseudo Second-order, Intra-partice and Elovic equation). Column elution experiments of Congo red and Cadmium from NLP and activated charcoal from NLP (AC-NLP) respectively was performed using selected eluent. Sorption and elution process plots and parameters for seven sorption–desorption cycles were evaluated and discussed. Plots of life cycle indicating activity-indicator equations were drawn, and their parameters were calculated and mentioned. From desorption efficiencies, it revealed that desorption exploration is predominately depends upon pH factor.

Can Alkyl Quaternary Ammonium Cations Substitute H2O2 in Controlling Cyanobacterial Blooms—Laboratory and Mesocosm Studies

Mitigation of harmful cyanobacterial blooms that constitute a serious threat to water quality, particularly in eutrophic water, such as in aquaculture, is essential. Thus, in this study, we tested the efficacy of selected cyanocides towards bloom control in laboratory and outdoor mesocosm experiments. Specifically, we focused on the applicability of a group of cationic disinfectants, alkyltrimethyl ammonium (ATMA) compounds and H2O2. The biocidal effect of four ATMA cations with different alkyl chain lengths was evaluated ex situ using Microcystis colonies collected from a fish pond. The most effective compound, octadecyl trimethyl ammonium (ODTMA), was further evaluated for its selectivity towards 24 cyanobacteria and eukaryotic algae species, including Cyanobacteria, Chlorophyta, Bacillariophyta, Euglenozoa and Cryptophyta. The results indicated selective inhibition of cyanobacteria by ODTMA-Br (C18) on both Chroccocales and Nostocales, but a minor effect on Chlorophytes and Bacillariophytes. The efficacy of ODTMA-Br (C18) (6.4 μM) in mitigating the Microcystis population was compared with that of a single low dose of H2O2 treatments (117.6 μM). ODTMA-Br (C18) suppressed the regrowth of Microcystis for a longer duration than did H2O2. The results suggested that ODTMA-Br (C18) may be used as an effective cyanocide and that it is worth further evaluating this group of cationic compounds as a treatment to mitigate cyanobacterial blooms in aquaculture.

Bactericidal Activity of a Self-Biodegradable Lysine-Containing Dendrimer against Clinical Isolates of Acinetobacter Genus

The genus Acinetobacter consists of Gram-negative obligate aerobic pathogens, including clinically relevant species, such as A. baumannii, which frequently cause hospital infections, affecting debilitated patients. The growing resistance to antimicrobial therapies shown by A. baumannii is reaching unacceptable levels in clinical practice, and there is growing concern that the serious conditions it causes may soon become incurable. New therapeutic possibilities are, therefore, urgently needed to circumvent this important problem. Synthetic cationic macromolecules, such as cationic antimicrobial peptides (AMPs), which act as membrane disrupters, could find application in these conditions. A lysine-modified cationic polyester-based dendrimer (G5-PDK), capable of electrostatically interacting with bacterial surfaces as AMPs do, has been synthesized and characterized here. Given its chemical structure, similar to that of a fifth-generation lysine containing dendrimer (G5K) with a different core, and previously found inactive against Gram-positive bacterial species and Enterobacteriaceae, the new G5-PDK was also ineffective on the species mentioned above. In contrast, it showed minimum inhibitory concentration values (MICs) lower than reported for several AMPs and other synthetic cationic compounds on Acinetobacter genus (3.2–12.7 µM). Time-kill experiments on A. baumannii, A. pittii, and A. ursingii ascertained the rapid bactericidal effects of G5-PDK, while subsequent bacterial regrowth supported its self-biodegradability.

The Alteration of L-Carnitine Transport and Pretreatment Effect under Glutamate Cytotoxicity on Motor Neuron-Like NSC-34 Lines

L-Carnitine (LC) is essential for transporting fatty acids to the mitochondria for β-oxidation. This study was performed to examine the alteration of the LC transport system in wild type (WT, NSC-34/hSOD1WT) and mutant type (MT, NSC-34/hSOD1G93A) amyotrophic lateral sclerosis (ALS) models. The uptake of [3H]L-carnitine was dependent on time, temperature, concentration, sodium, pH, and energy in both cell lines. The Michaelis–Menten constant (Km) value as well as maximum transport velocity (Vmax) indicated that the MT cell lines showed the higher affinity and lower capacity transport system, compared to that of the WT cell lines. Additionally, LC uptake was inhibited by organic cationic compounds but unaffected by organic anions. OCTN1/slc22a4 and OCTN2/slc22a5 siRNA transfection study revealed both transporters are involved in LC transport in NSC-34 cell lines. Additionally, slc22a4 and slc22a5 was significantly decreased in mouse MT models compared with that in ALS WT littermate models in the immune-reactivity study. [3H]L-Carnitine uptake and mRNA expression pattern showed the pretreatment of LC and acetyl L-carnitine (ALC) attenuated glutamate induced neurotoxicity in NSC-34 cell lines. These findings indicate that LC and ALC supplementation can prevent the neurotoxicity and neuro-inflammation induced by glutamate in motor neurons.

Influence of YES1 Kinase and Tyrosine Phosphorylation on the Activity of OCT1

Organic cation transporter 1 (OCT1) is a transporter that regulates the hepatic uptake and subsequent elimination of diverse cationic compounds. Although OCT1 has been involved in drug-drug interactions and causes pharmacokinetic variability of many prescription drugs, details of the molecular mechanisms that regulate the activity of OCT1 remain incompletely understood. Based on an unbiased phospho-proteomics screen, we identified OCT1 as a tyrosine-phosphorylated transporter, and functional validation studies using genetic and pharmacological approaches revealed that OCT1 is highly sensitive to small molecules that target the protein kinase YES1, such as dasatinib. In addition, we found that dasatinib can inhibit hepatic OCT1 function in mice as evidenced from its ability to modulate levels of isobutyryl L-carnitine, a hepatic OCT1 biomarker identified from a targeted metabolomics analysis. These findings provide novel insight into the post-translational regulation of OCT1 and suggest that caution is warranted with polypharmacy regimes involving the combined use of OCT1 substrates and kinase inhibitors that target YES1.