GREEN TEA EXTRACT IN MICROEMULSION: STABILITY, DERMAL SENSITIZATION AND EFFICACY AGAINST UV INDUCED DAMAGES

Objective: To determine the photoprotective effect of epigallocatechin (EGC) extracted from green tea using microemulsions as a carrier system.Methods: In the present study, EGC was extracted from commercially available branded as well as loose green tea samples. Further, microemulsions (MEs) of these extracts were formulated and were evaluated for their antioxidant and photoprotective effects. MEs were formulated using Capmul MCM as oily phase, Tween 80 as a surfactant and Labrasol as co-surfactant after studying the phase behavior. MEs containing green tea extracts were applied to the rat dorsal skin after exposure to UV radiation (rate of exposure = 9.71 J/cm2, dose = 0.9011 mJ/cm2/sec). The effect of the formulation was evaluated in terms of reduced glutathione level (GSH), radical scavenging activity (DPPH), trans-epidermal water loss (TEWL), irritation potential and histological changes. The EGC content of both types of green tea was estimated using HPTLC and photo-stability of ME formulation was evaluated using FTIR-ATR technique.Results: The content of EGC in loose and branded tea leaf extracts was found to be 0.00322 % w/w and 0.00468 % w/w, respectively. FTIR studies revealed the instability of formulations prepared with water as aqueous phase after UV exposure. However, in the case of PB (pH 7.4) as the aqueous phase in MEs; no change in the spectra of formulations after UV exposure for different time intervals was observed. Results of TEWL studies indicated that the barrier perturbation was not severe which clearly states the safety aspect of the formulation. The extinction coefficient (EC50) value for loose tea and branded tea leaf extract was found to be 170 µg/ml and 79 µg/ml, respectively. The yield of the extract was 0.00322±0.026 % w/w for loose tea and 0.00468±0.150 % w/w for branded tea.Conclusion: The results of the present investigation indicated that pH of the aqueous phase used for preparing the formulation affected the photo-stability of the formulation. Further, MEs prepared using green tea extracts exhibited photoprotective effects. Hence, the green tea extract containing ME formulations have promising potential to be a cosmeceutical.Keywords: Efficacy against uv induced damages, Microemulsion, Dermal sensitizatio

The physicochemistry and percolation behavior of microemulsions as a function of chain length of cosurfactant and surfactant

This study involved investigating phase behavior and physicochemical characterization of microemulsions (MEs) stabilized by mixtures containing polysorbates (C12-C18) as surfactants and n-alkanols (C2-C6) as cosurfactants. Distribution coefficients and Gibbs free energy were also determined for the systems containing polyoxyethylene sorbitan monolaurate (Tween® 20) as surfactant. ME with Tween® 20 as the surfactant and ethanol as the co surfactant exhibited maximium ME area, as well as, water solubilization capacity (WSC). In the presence of all the cosurfactants, values of both of these parameters decreased as the chain length of the surfactant increased with the exception of Tween® 80. This could be attributed to the unsaturated structure of Tween® 80 which possibly allowed for greater spatial configurations of the chain and thus allowing less oil penetration. Furthermore, the transition of w/o MEs to o/w MEs via a bi-continuous structure along the dilution line was confirmed by conductivity, viscosity and droplet size analysis

Physicochemistry and Percolation behavior of Microemulsions as a Function of Chain Length of Cosurfactant and Surfactant

The study involved investigations on phase behavior and physicochemical characterization of microemulsions (MEs) stabilized by mixture containing polysorbates (C12-C18) as surfactants and n-alkanols (C2-C6) as cosurfactant. Distribution coefficient and Gibbs free energy were also determined for systems containing Tween 20 as surfactant. ME having Tween 20 as surfactant and ethanol as cosurfactant was found to exhibit maximium ME region as well as water solubilization capacity (WSC). Values of both these parameters were found to decrease as chain length of surfactant increased in all cases of alkanols with exception of Tween 80. This could be attributed to unsaturated structure of Tween 80 which presumably caused folding of chain and lesser oil penetration. Furthermore, the transition of w/o MEs to o/w MEs via bicontinuous structure along the dilution line was confirmed by conductivity, viscosity and droplet size analysis

Morphology, morphogenesis, and molecular phylogeny of Sterkiella tetracirrata n. sp. (Ciliophora, Oxytrichidae), from the Silent Valley National Park, India

The morphology and morphogenesis during cell division of Sterkiella tetracirrata n. sp., isolated from a soil sample collected from the Silent Valley National Park, Kerala, India, were investigated using live observation, protargol staining and scanning electron microscopy. The new species differs from its congeners by the following combination of features: cell size in vivo 85–110×35–50 m, on average 84×37 m in protargol preparations; four ellipsoidal macronuclear nodules; 31 adoral membranelles; 17 frontal-ventral-transverse cirri consisting of three frontal, four frontoventral, one buccal, three ventral, two pretransverse and invariably four transverse cirri; resting cyst with separate macronuclear nodules. Sterkiella tetracirrata differs from the similar species S. terricola in the number of transverse cirri (invariably 4 vs. 3) and in the number of adoral membranelles (24–35 vs. 22 or 23). Morphogenesis resembles that of its congeners S. nova and S. histriomuscorum. Phylogenetic analyses based on SSU rRNA gene sequences consistently place the new species within the stylonychine oxytrichids, clustering closer to Gastrostyla steinii than to either S. cavicola or S. histriomuscorum. The analyses support the morphological evidence (e.g., similarity in the oral apparatus and the dorsal kinety pattern) that Gastrostyla and Pattersoniella evolved from a Sterkiella-like ancestor

Machine Learning Enabled Structure-Based Drug Repurposing Approach to Identify Potential CYP1B1 Inhibitors

Drug-metabolizing enzyme (DME)-mediated pharmacokinetic resistance of some clinically approved anticancer agents is one of the main reasons for cancer treatment failure. In particular, some commonly used anticancer medicines, including docetaxel, tamoxifen, imatinib, cisplatin, and paclitaxel, are inactivated by CYP1B1. Currently, no approved drugs are available to treat this CYP1B1-mediated inactivation, making the pharmaceutical industries strive to discover new anticancer agents. Because of the extreme complexity and high risk in drug discovery and development, it is worthwhile to come up with a drug repurposing strategy that may solve the resistance problem of existing chemotherapeutics. Therefore, in the current study, a drug repurposing strategy was implemented to find the possible CYP1B1 inhibitors using machine learning (ML) and structure-based virtual screening (SB-VS) approaches. Initially, three different ML models were developed such as support vector machines (SVMs), random forest (RF), and artificial neural network (ANN); subsequently, the best-selected ML model was employed for virtual screening of the selleckchem database to identify potential CYP1B1 inhibitors. The inhibition potency of the obtained hits was judged by analyzing the crucial active site amino acid interactions against CYP1B1. After a thorough assessment of docking scores, binding affinities, as well as binding modes, four compounds were selected and further subjected to in vitro analysis. From the in vitro analysis, it was observed that chlorprothixene, nadifloxacin, and ticagrelor showed promising inhibitory activity toward CYP1B1 in the IC50 range of 0.07–3.00 μM. These new chemical scaffolds can be explored as adjuvant therapies to address CYP1B1-mediated drug-resistance problems

Scaffold hopping for designing of potent and selective CYP1B1 inhibitors to overcome docetaxel resistance: synthesis and evaluation

Cytochrome P450 1B1, a tumor-specific overexpressed enzyme, significantly impairs the pharmacokinetics of several commonly used anticancer drugs including docetaxel, paclitaxel and cisplatin, leading to the problem of resistance to these drugs. Currently, there is no CYP1B1 inhibition-based adjuvant therapy available to treat this resistance problem. Hence, in the current study, exhaustive in-silico studies including scaffold hopping followed by molecular docking, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular dynamics and free energy perturbation studies were carried out to identify potent and selective CYP1B1 inhibitors. Initially, scaffold hopping analysis was performed against a well-reported potent and selective CYP1B1 inhibitor (i.e. compound 3n). A total of 200 scaffolds were identified along with their shape and field similarity scores. The top three scaffolds were further selected on the basis of these scores and their synthesis feasibility to design some potent and selective CYP1B1 inhibitors using the aforementioned in-silico techniques. Designed molecules were further synthesized to evaluate their CYP1B1 inhibitory activity and docetaxel resistance reversal potential against CYP1B1 overexpressed drug resistance MCF-7 cell line. In-vitro results indicated that compounds 2a, 2c and 2d manifested IC50 values for CYP1B1 ranging from 0.075, 0.092 to 0.088 μM with at least 10-fold selectivity. At low micromolar concentrations, compounds 1e, 1f, 2a and 2d exhibited promising cytotoxic effects in the docetaxel-resistant CYP1B1 overexpressed MCF-7 cell line. In particular, compound 2a is most effective in reversing the resistance with IC50 of 29.0 ± 3.6 μM. All of these discoveries could pave the way for the development of adjuvant therapy capable of overcoming CYP1B1-mediated resistance. Communicated by Ramaswamy H. Sarma</p

Formulation and evaluation of ethosomes for transdermal delivery of lamivudine

The purpose of the present research was to investigate the mechanism for improved intercellular and intracellular drug delivery from ethosomes using visualization techniques and cell line study. Ethosomal formulations were prepared using lamivudine as model drug and characterized in vitro, ex vivo and in vivo. Transmission electron microscopy, scanning electron microscopy, and fluorescence microscopy were employed to determine the effect of ethosome on ultrastructure of skin. Cytotoxicity and cellular uptake of ethosome were determined using T-lymphoid cell line (MT-2). The optimized ethosomal formulation showed 25 times higher transdermal flux (68.4±3.5 µg/cm2/h) across the rat skin as compared with that of lamivudine solution (2.8±0.2 µg/cm2/h). Microscopic studies revealed that ethosomes influenced the ultrastructure of stratum corneum. Distinct regions with lamellar stacks derived from vesicles were observed in intercellular region of deeper skin layers. Results of cellular uptake study showed significantly higher intracellular uptake of ethosomes (85.7%±4.5%) as compared with drug solution (24.9%±1.9%). The results of the characterization studies indicate that lipid perturbation along with elasticity of ethosomes vesicles seems to be the main contributor for improved skin permeation