Gums are naturally occurring components in plants, which are essentially cheap and plentiful. They have diverse applications as thickeners, emulsifiers, viscosifiers, sweeteners etc. in ...confectionary, and as binders and drug release modifiers in pharmaceutical dosage forms. However, most of the gums in their putative form are required in very high concentrations to successfully function as drug release modifiers in dosage forms due to their high swellability/solubility at acidic pH. Hence, gums need to be modified to alter their physicochemical properties. This article is aimed at discussing the modification of gums through derivatisation of functional groups, grafting with polymers, cross-linking with ions etc. The factors influencing these processes in the pursuit of making them suitable for modifying the drug release properties of pharmaceutical dosage forms and for other purposes is discussed with respect to optimization of their performance.
The objective of the study was to optimize the proportion of different components for formulating oil in water microemulsion formulation meant for simultaneous transdermal delivery of two poorly ...soluble antihypertensive drugs. Surface response methodology of Box-Behnken design was utilized to evaluate the effect of two oils (Captex 500 - x1 and Capmul MCM - x2) and surfactant (Acrysol EL135 - x3) on response y1 (particle size), y2 (solubility of valsartan), and y3 (solubility of nifedipine). The important factors which significantly affected the responses were identified and validated using ANOVA. The model was diagnosed using normal plot of residuals and Box-Cox plot. The design revealed an inverse correlation between particle size and concentration of Capmul MCM and Acrysol EL 135. However, an increase in concentration of Captex 500 led to an increase in particle size of microemulsion. Solubility of valsartan decreased while that of nifedipine increased with increase in concentration of Captex 500. Capmul MCM played a significant role in increasing the solubility of valsartan. The effect of Acrysol EL 135 on solubility of both drugs, although significant, was only marginal as compared to that of Captex 500 and Capmul MCM. The optimized microemulsion was able to provide an enhancement ratio of 27.21 and 63.57-fold for valsartan and nifedipine, respectively, with respect to drug dispersion in aqueous surfactant system when evaluated for permeation studies. The current studies candidly suggest the scope of microemulsion systems for solubilizing as well as promoting the transport of both drugs across rat skin at an enhanced permeation rate.
The objective of the present investigation was to prepare and optimize lyophilized mixed micelles (Lyp‐EXE‐MMs) of exemestane (EXE) with improved solubility, bioavailability, in vivo anticancer ...activity, and physical stability, by using various cryoprotectants. The prepared lyophilized mixed micelles were characterized by various techniques, including dynamic light scattering, zeta potential, powdered X‐ray diffraction, differential scanning calorimetry (DSC), nuclear magnetic resonance (1H NMR), transmission electron microscopy (TEM), and so on. Thereafter, the lyophilized micelles were evaluated for ex vivo permeation, in vitro drug release and gene/protein expression (RT‐PCR and Western blot analysis) in MCF‐7 breast cancer cells. The developed formulation was also investigated for its in vivo anticancer study in BALB/c mice with induced breast cancer. The use of trehalose (10% w/w) was proven to be a suitable cryoprotectant for these micelles. Lyp‐EXE‐MMs were spherical, with a particle size of 42.9 ± 3.8 nm and a polydispersity index of 0.307 ± 0.122. Furthermore, % drug loading and % entrapment efficiency were found to be 5.8 ± 1.4 and 89.1 ± 1.1, respectively. Lyp‐EXE‐MMs showed sustained release behavior as compared to EXE‐suspensions in SGF/SIF (pH 1.2 and 6.8) and phosphate buffer saline (pH 7.4). The micelles induced apoptosis through the regulation of BAX, BCL2, Caspase‐3, p53, and CYP19A1 in MCF‐7 cells, which was correlated to enhanced ex vivo drug permeation. Animals receiving EXE micelle formulations showed reduced tumor volume and improved survivability and pharmacokinetic parameters as compared to pure EXE. Lyp‐EXE‐MMs were found to withstand simulated harsh conditions of SGF/SIF during stability studies. The fabricated EXE micellar preparations hold a promising approach for breast cancer treatment.
Lyophilized mixed micelles of exemestane (EXE) were prepared and optimized to have improved solubility, bioavailability, in vivo anticancer activity, and physical stability, by using various cryoprotectants. Animals receiving EXE micelle formulations showed reduced tumor volume and improved survival and pharmacokinetic parameters, as compared to pure EXE.
Non‐availability of fresh water is the dire consequence of rapid industrialization and the unregulated discharge of industrial effluents. In an attempt to recover water from highly contaminated ...industrial wastewater, researchers have relied on developing various materials that can treat polluted water efficiently and sustainably. 3D printed materials have proved to be an emerging technology in water treatment. 2D materials have recently enhanced filter technology due to their morphological properties. This study focuses on removing salinity and organic dyes utilizing 2D Gadolinium telluride (Gd2Te3 ) coated 3D printed (2D@3DP) complex architecture. The 2D@3DP structure can potentially increase the contact time of adsorbed saline water due to its complex architecture and can remove ≈52% salinity from brackish water. Furthermore, methylene blue (MB) and Methyl Orange (MO) removal efficiencies are ≈69% and 45%, respectively. Spectroscopic and microscopic results confirm the adsorption of negatively charged chlorine ions on a positively charged 2D surface. The removal of bleaching powder is also tested for real‐life applications, and ≈20% of the bleaching powder is adsorbed. Moreover, the 2D@3DP device exhibits an electrical signal due to impinging sodium chloride droplets from different heights, making it a sustainable solution to address water pollution.
A novel 3D‐printed architecture is designed with the coating of 2D Gadolinium telluride to demonstrate smart wastewater management. The porosity and high surface area of the 3D‐printed system exhibit salt removal efficiency by employing the synergistic effect of polymer and 2D Gd2Te3. The research advances knowledge about the effectiveness of wastewater treatment combined with sustainable energy generation.
The present investigation attempts to optimize Supersaturable lipid based formulation (SS SMEDDS) of Biopharmaceutical Classification System (BCS) class IV drug canagliflozin (CFZ) and evaluating the ...oral bioavailability of the formulation.
Preliminary screening revealed Poloxamer 188 to most effectively inhibit precipitation of CFZ after dispersion during in vitro supersaturation studies. Box Behnken Design was employed for designing different formulations, and various statistical analyses were done to select an appropriate mathematical model. The optimized formulation (OSS 1) was evaluated for in vitro drug release and ex vivo permeation studies to evaluate drug release and permeation rate. Pharmacokinetic studies have been carried out according to standard methodologies.
The optimized formulation (OSS 1) containing 781.1 mg SS SMEDDS and 2.24% w/w Poloxamer 188 was developed at a temperature of 60°C, which revealed nano-globule size with negligible aggregation. Isothermal titration calorimetry revealed the thermodynamic state of formed microemulsion with negative ΔG. The optimized formulation was observed to possess physical stability under different stress conditions and acceptable drug content. In vitro dissolution of optimized SS SMEDDS revealed a higher dissolution rate of CFZ as compared to native forms of CFZ. The permeability of CFZ from optimized SS SMEDDS across various excised segments of rat intestine was observed to be multifold higher as manifested by 2.05-fold higher Cmax and 5.64- fold higher AUC0-36h following oral administration to Wistar rats.
The results could be attributed to substantial lymphatic uptake and P-glycoprotein substrate affinity of CFZ in SS SMEDDS investigated through chylomicron and P-glycoprotein inhibition approach, respectively.
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 microg/cm(2)/h) across the rat skin as compared with that of lamivudine solution (2.8 +/- 0.2 microg/cm(2)/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.
An isolate, designated as Bacillus sp. AKD1, based on the 16S rRNA gene sequence, could transform 86% ± 3.6% of cypermethrin (initial concentration of 100 ppm) in 7 days, but biotransformation was ...inhibited at concentrations above 150 ppm. As determined by the Response Surface Methodology (RSM), optimum parameters for the biotransformation were: pH value of 8.0, temperature of 37.8 °C and inoculum density of 4.4 mg ml−1 (wet wt.). Glucose, fructose and glycerol inhibited insecticide biotransformation at concentrations above 0.5%, 1.0% and 0.5 respectively (w/v). Minimum inhibitory concentrations of Bacillus sp. AKD1 for Co2+, Cr6+, Cu2+, Fe2+, Li+, Ni2+, pb2+, V5+ and Zn2+ were 0.2 mM, 1.4 mM, 1.8 mM, 5.1 mM, 7.8 mM, 2.9 mM, 0.6 mM, 8.2 mM, and 0.6 mM respectively. At concentrations less than the MIC, V5+ and Fe2+ did not affect cypermethrin biotransformation, but Li+ was found to be inhibitory above 4.0 mM. The results obtained in this study have significant importance in the development of bioremediation strategy for removal of cypermethrin in cypermethrin contaminated areas co-contaminated with heavy metals.
•Cypermethrin degradation by heavy metal tolerant Bacillussp. AKD1.•AKD1 efficiently bio-transformed cypermethrin in presence of high concentration of Li2+, Fe2+ and V5+.•Bacillus sp. AKD1 was identified as a novel strain of Bacillus cereus group.
The aim of the present investigation is to systematically optimize and develop microemulsion preconcentrates to improve the solubility and oral bioavailability profile of canagliflozin employing ...D-optimal mixture design. Preconcentrate constituents, i.e. oils, surfactants and co-surfactants were selected on the basis of solubility studies and their concentration range capable of influencing the formation of microemulsions was determined. D-optimal mixture design was employed for studying the interaction behavior of desired responses and optimized using desirability approach. The optimized formulation was evaluated for its in vitro, ex vivo and in vivo behavior to determine the dissolution rate, permeation rate and oral bioavailability of the drug. The optimized formulation containing Lauroglycol FCC (80 mg), Tween 80 (300 mg) and Transcutol P (120 mg) showed desired attributes of measured responses with minimum experimental variation and desirability value of 0.751. The morphological behavior showed uniform nano-structured globules with negligible aggregation as confirmed in transmission electron microscopy. Ex vivo permeation rate of the drug across excised intestinal segments (duodenum, jejunum, ileum and colon) was observed to be 3.51, 5.62, 4.52 and 2.98 folds higher, respectively, as compared to drug powder and marketed tablets Compared with the pure drug and commercial tablets, enhanced in vitro dissolution rate of optimized formulation was observed, resulting in 2.56 fold enhancement in C
max
and AUC
0–24h
following oral administration in fasting wistar rats. Establishment of level A IVIVC for the developed SMEDDS indicated excellent goodness of fit between the in vitro drug release and in vivo drug absorbed. Accelerated stability studies indicated stability of the optimized formulation over 3 months storage.
Type 2 Diabetes Mellitus (T2DM) is one of the prevalent metabolic disorders and is the leading cause of death across the globe. In the present invention, we reported significant synergistic ...anti-diabetic efficacy of novel SGLT II inhibitor, Canagliflozin (CFZ) with natural phytoconstituent, Trigonelline (TGL) in fenugreek oil using a self-microemulsifying based formulation. The optimized liquid SMEDD formulation (NADF) containing fenugreek oil (18.11% w/w), vitamin E TPGS (53.40% w/w) and linalool (10.12% w/w) were optimized by Design of Experiments and produces nanoparticulate stable microemulsion in vitro. Conversion to solid SMEDDS (NADF-SD) was facilitated by adsorption onto natural biosorbent coffee husk. The optimized solid formulation containing CFZ was in amorphous state with enhanced surface area, negligible chemical incompatibility and uniform drug content. Scanning electron microscopy validated the powdered SMEDDS′ spherical form. The release behavior of CFZ in NADF-SD in diverse biorelevant environments is enhanced by in vitro dissolution. Furthermore, neither pure CFZ nor the marketed product had any food impact. The permeability of the jejunum intestinal segment in rats was remarkable, as validated by confocal microscopy. In comparison to a pure drug and a commercial product, these trials show a 3.99 and 2.56 fold increase in Cmax and a 2.23 and 1.56 fold increase in AUC0-24h, respectively. Through biochemical levels, urine glucose excretion investigations, and SGLT II expression in rats, pharmacodynamic examination of improved NADF-SD demonstrates enhanced anti-diabetic effectiveness of CFZ. In a nutshell, this natural lipid-based micro particulate system is well-suited for this drug's anti-diabetic activity and synergy with CFZ.
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Macrophages of the reticuloendothelial system and brain act as major reservoir for HIV because of their long term survival after HIV infection and ability to spread virus particles to bystander CD4 ...positive lymphocyte cells. The objective of the present study was to investigate mannan-coated nanoparticles for macrophage targeting of didanosine. Different didanosine loaded nanoparticles were prepared using the double desolvation technique and were characterized in vitro, ex vivo and in vivo. Results of the ex vivo cellular uptake study indicated 5--fold higher uptake of didanosine from the mannan-coated nanoparticles formulation (62.5 ± 5.4%) by the macrophages in comparison with didanosine solution in phosphate buffer saline (PBS, pH 7.4) (12.1 ± 2.3%). The better cellular uptake from the nanoparticles formulation was further confirmed by fluorescence microscopy using hydrophilic 6-carboxyfluorescein as a marker. Results of the quantitative biodistribution study showed 1.7, 12.6 and 12.4 times higher localization of didanosine in the spleen, lymph nodes and brain, respectively, after administration of mannan-coated nanoparticles compared to that after injection of didanosine solution in PBS (pH 7.4). Results of the present study showed that the mannan-coated nanoparticles targeted didanosine to the macrophage by mannosyl receptor mediated endocytosis.
Makrofagi retikuloendotelnog sustava i mozak djeluju kao glavni rezervoari za HIV zbog njihovog dugoročnog preživljavanja nakon infekcije HIV-om i sposobnosti da usmjere virusne čestice u CD4 pozitivne limfocite. Cilj rada bio je ispitati nanočestice obložene mananom za ciljanu isporuku didanozina u makrofage. Koristeći metodu dvostruke desolvatacije pripravljene su različite nanočestice s didanozinom te su zatim karakterizirane in vitro, ex vivo i in vivo. Rezultati ex vivo ispitivanja ukazuju da je unos didanozina u makrofage 5 puta veći iz nanočestica obloženih mananom (62,5 ± 5,4%) u usporedbi s otopinom didanozina u fosfatnom puferu (PBS, pH 7,4) (12,1 ± 2,3%). Bolji celularni unos iz nanočestica potvrđen je fluorescentnom mikroskopijom koristeći hidrofilni 6-karboksifluorescein kao marker. Rezultati kvantitativne biodistribucije pokazuju da je lokalizacija didanozina u slezeni, limfnim čvorovima i mozgu 1,7, 12,6, odnosno 12,4 puta veća nakon primjene nanočestica obloženih mananom nego nakon primjene otopine didanozina u PBS-u (pH 7,4). Nanočestice s mananom usmjeravaju didanozin u makrofage procesom endocitoze u kojoj posreduju receptori za manozu.
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