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Objective: This investigation has focused to characterize the elastic liposome containing 5-fluorouracil (5-FU) and to enhance drug permeation across stratum corneum (SC) of the skin (rat) using various surfactants andin vivodermal toxicity evaluation. Methodology: 5-FU-loaded elastic liposomes were developed, prepared and characterized for their entrapment efficiency, vesicle size, number of vesicles, morphological characteristics, surface charge and turbidity.In vitrodrug release profile,in vitroskin permeation potential andin vitrohemolytic ability of the formulation have been evaluated to compare with drug solution for 24 h.In vitroskin permeation potential was also compared with marketed cream. Furthermore,in vivoskin irritation potential, drug penetration into the skin using confocal laser scanning microscopy (CLSM) andin vivotoxicity studies were performed. Results and conclusions: The optimized elastic liposomes demonstrated maximum drug entrapment efficiency, optimum vesicular size and considerable elasticity.In vitroskin permeation studies showed the highest drug permeation flux like 77.07 ± 6.34, 89.74 ± 8.5 and 70.90 ± 9.6 µg/cm2/h for EL3-S60, EL3-S80 and EL3-T80, respectively, as compared to drug solution (8.958 ± 6.9 µg/cm2/h) and liposome (36.80 ± 6.4 µg/cm2/h). Drug deposition of optimized elastic liposome EL3-S80 was about three fold higher than drug solution. Skin irritation and CLSM studies suggested that optimized gel was free from skin irritation and capable to deliver 5-FU into the epidermal area for enhanced topical delivery than drug solution. Thein vitrostudy showed minimum hemolysis in the optimized formulation. Finally,in vivotoxicity studies followed with hisptopathological assessment showed that elastic liposome was able to extract SC to improve drug permeation without changing general anatomy of the skin. [ABSTRACT FROM PUBLISHER]

Aim: To characterize the enhanced stability and permeation potential of amphotericin B nanoemulsion comprising sefsol-218 oil at varying pH and temperature of aqueous continuous phase. Methodology: Several batches of amphotericin B loaded nanoemulsion were prepared and evaluated for their physical and chemical stability at different pH and temperature. Also, a comparative study of ex vivo drug permeation across the albino rat skin was investigated with commercial Fungisome® and drug solution at 37 °C for 24 h. The extent of drug penetrated through the rat skin was thereby evaluated using the confocal laser scanning microscopy (CLSM). Results and conclusions: The optimized nanoemulsion demonstrated the highest flux rate 17.85 ± 0.5 µg/cm2/h than drug solution (5.37 ± 0.01 µg/cm2/h) and Fungisome® (7.97 ± 0.01 µg/cm2/h). Ex vivo drug penetration mechanism from the developed formulations at pH 6.8 and pH 7.4 of aqueous phase pH using the CLSM revealed enhanced penetration. Ex vivo drug penetration studies of developed formulation comprising of CLSM revealed enhanced penetration in aqueous phase at pH 6.8 and 7.4. The aggregation behavior of nanoemulsion at both the pH was found to be minimum and non-nephrotoxic. The stability of amphotericin B was obtained in terms of pH, optical density, globular size, polydispersity index and zeta potential value at different temperature for 90 days. The slowest drug degradation was observed in aqueous phase at pH 7.4 with shelf life 20.03-folds higher when stored at 4 °C (3.8 years) and 5-fold higher at 25 °C (0.951 years) than at 40 °C. The combined results suggested that nanoemulsion may hold an alternative for enhanced and sustained topical delivery system for amphotericin B. [ABSTRACT FROM AUTHOR]

The primary aim of the study was to observe the morphological changes taking place onEscherichia coliwhen treated with non-cationised placebo lipidic emulsion (NCPLE) and cationised placebo lipidic emulsion (CPLE). The particle size of NCPLE and CPLE indicated the mean diameter of 10.77 ± 0.20 nm and 56.98 ± 1.718 nm, respectively. The zeta potential of NCPLE and CPLE depicted the potential of −10.8 ± 0.80 mV and +20.9 ± 3.25 mV, respectively. Agar diffusion study indicated higher inhibition zone of 21.4 ± 0.85 mm for CPLE as evaluated against 14.7 ± 0.76 mm for NCPLE. Transmission electron micrographs ofEscherichia colitreated with NCPLE and CPLE showed the potential of blank nanoemulsions as antibacterial, which can be used as a therapeutic agent. The bacterial cell being negatively charged attracts the cationised nanoemulsions from the bulk of dispersion. As the concentration of nanoemulsion increased in the vicinity of the bacterial cell, the degree of collisions increased between the cationised nanoemulsion leading to coalescence and the formation of a pool of emulsion containing bacterial cells leading to cell death. The study demonstrated that placebo lipidic nanoemulsion (NCPLE & CPLE) may itself be used as an active therapeutic agent for the treatment of bacterial infections. Moreover, it can also be used as a carrier system for antibacterial drugs for the two-pronged synergistic effect. [ABSTRACT FROM AUTHOR]

Objective: To design and develop liquid and solid self-nanoemulsifying drug delivery systems (SNEDDS and S-SNEDDS) of felodipine (FLD) using Box-Behnken design (BBD). Methods: Solubility study was carried out in various vehicles. Ternary phase diagram was constructed to delineate the boundaries of the nanoemulsion domain. The content of formulation variables, X1 (Acconon E), X2 (Cremophor EL) and X3 (Lutrol E300) were optimized by assessment of 15 formulations (as per BBD) for mean globule sizes in Millipore water (Y1), 0.1 N HCl (Y2), phosphate buffer (pH 6.4) (Y3); emulsification time (Y4) and T85% (Y5). The responses (Y1-Y5) were evaluated statistically by analysis of variance and response surface plots to obtain optimum points. The optimized formulations were solidified by adsorption to solid carrier technique using Aerosil 200 (AER). Results and discussion: Transmission electron microscopy images confirmed the spherical shape of globules with the size range concordant with the globule size analysis by dynamic light scattering technique (<60 nm). The surface morphology of S-SNEDDS (before release) by scanning electron microscopy and atomic force microscopy indicated that SNEDDS are adsorbed uniformly on the surface of AER. The dried residue of S-SNEDDS (after release) revealed the presence of nanometric pores vacated by the previously adsorbed SNEDDS onto AER. Differential scanning calorimetry and X-ray powder diffraction studies illustrated the change of FLD from crystalline to amorphous state. Conclusion: This study indicates that owing to nanosize, SNEDDS and S-SNEDDS of FLD have potential to enhance its absorption and may serve an efficient oral delivery. [ABSTRACT FROM AUTHOR]

G-Quadruplex (GQ) is a secondary structural unit of DNA, formed at the telomere region of the chromosome with a high guanine content. It is reported that the GQs can hinder many biological processes. Thus, research thrives to explore the structural stability of GQs. Studies based on circular dichroism (CD) and nuclear magnetic resonance (NMR) experiments established the vital role of cations such as K + and Mg 2+ in the stability of antiparallel G-quadruplexes (AGQs). However, there is a need to understand how stability in AGQ is attained in the presence of cations. Here, we employed molecular dynamics (MD) simulations, steered MD (SMD) simulations, and QM/MM calculations to understand the biophysical and electronic bases of the stability imparted to AGQs via cation binding. Our results showed that Mg 2+ prefers to bind in the plane with the guanine tetrad, whereas K + binds in between the AGQ tetrads. Thus, three Mg 2+ cations or two K + ions are needed to stabilize an AGQ molecule, where each and every tetrad binds to Mg 2+ more robustly with a higher binding affinity. SMD revealed that the traversal of K + through the AGQ central channel required less force than that of Mg 2+ , illustrating the presence of more strong interactions between Mg 2+ and AGQ tetrads compared to K + . The stabilization in the AGQ tetrads due to cation binding is reassessed by employing ab initio simulations. Mixed QM/MM calculations confirmed that Mg 2+ binds strongly to AGQ compared to K + , and it induces higher interactions between the guanine tetrads. However, K + binding to AGQ induces a higher stabilization energy than Mg 2+ binding to AGQ tetrads. Despite the higher binding energy, Mg 2+ binding imparts lower stabilization to AGQ due to its unfavorable fermionic quantum energy.

The in vivo antioxidant properties of green tea extract (GTE) were investigated against doxorubicin (DOX) induced cardiotoxicity in rats. In this experiment, 48 Wistar albino rats (200-250 g) were divided into eight groups (n = 6). Control group received normal saline for 30 days. Cardiotoxicity was induced by DOX (20 mg/kg ip.), once on 29th day of study and were treated with GTE (100, 200 and 400 mg/kg, p.o.) for 30 days. Aspartate aminotransferase (AST), creatinine kinase (CK), lactate dehydrogenase (LDH), lipid peroxidation (LPO), cytochrome P450 (CYP), blood glutathione, tissue glutathione, enzymatic and non-enzymatic antioxidants were evaluated along with histopathological studies. DOX treated rats showed a significant increased levels of AST, CK, LDH, LPO and CYP, which were restored by oral administration of GTE at doses 100, 200 and 400 mg/kg for 30 days. Moreover, GTE administration significantly increased the activities of glutathione peroxidase (GPX), glutathione reductase (GR), glutathione s-transferase (GST), superoxide dismutase (SOD) and catalase (CAT), in heart, which were reduced by DOX treatment. In this study, we have found that oral administration of GTE prevented DOX-induced cardiotoxicity by accelerating heart antioxidant defense mechanisms and down regulating the LPO levels to the normal levels.