Amol A. Tatode

Bio: Amol A. Tatode is an academic researcher from Rashtrasant Tukadoji Maharaj Nagpur University. The author has contributed to research in topics: Nanocarriers & Kaempferol. The author has an hindex of 4, co-authored 8 publications receiving 50 citations.

Kaempferol-Phospholipid Complex: Formulation, and Evaluation of Improved Solubility, In Vivo Bioavailability, and Antioxidant Potential of Kaempferol

Abstract: The current work describes the formulation and evaluation of a phospholipid complex of kaempferol to enhance the latter’s aqueous solubility, in vitro dissolution rate, in vivo antioxidant and hepatoprotective activities, and oral bioavailability The kaempferol-phospholipid complex was synthesized using a freeze-drying method with the formulation being optimized using a full factorial design (32) approach Our results include the validation of the mathematical model in order to ascertain the role of specific formulation and process variables that contribute favorably to the formulation’s development The final product was characterized and confirmed by Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), Proton Nuclear Magnetic Resonance Spectroscopy (1H-NMR), and Powder X-ray Diffraction (PXRD) analysis The aqueous solubility and the in vitro dissolution rate were enhanced compared to that of pure kaempferol The in vivo antioxidant properties of the kaempferol-phospholipid complex were evaluated by measuring its impact on carbon tetrachloride (CCl4)-intoxicated rats The optimized phospholipid complex improved the liver function test parameters to a significant level by restoration of all elevated liver marker enzymes in CCl4-intoxicated rats The complex also enhanced the in vivo antioxidant potential by increasing levels of GSH (reduced glutathione), SOD (superoxide dismutase), catalase and decreasing lipid peroxidation, compared to that of pure kaempferol The final optimized phospholipid complex also demonstrated a significant improvement in oral bioavailability demonstrated by improvements to key pharmacokinetic parameters, compared to that of pure kaempferol

Development and Validation of UV Spectrophotometric Method for the Estimation of Kaempferol in Kaempferol: Hydrogenated Soy PhosphatidylCholine (HSPC) Complex

Abstract: Introduction: Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a natural flavonoid belongs to subcategory of flavonol family. The Kaempferol – Hydrogenated Soy Phosphatidylcholine (HSPC) Complex was obtained by refluxing and freeze drying method. UV – Visible Spectrophotometric method has been developed for determination of Kaempferol in Kaempferol – HSPC Complex. Objective: A validated UV – Visible spectrophotometric method for determination of Kaempferol in Kaempferol – HSPC complex. Methods: The Kaempferol – HSPC Complex (Phytosomes) were prepared by dissolving both Kaempferol and Hydrogenated Soy Phosphatidylcholine (HSPC) in 1, 4 – dioxane for refluxing up to 2h and freeze dried. The spectrophotometric detection of kaempferol was done at absorption maximum (λmax) of 365 nm and 265 nm using methanol as solvent. The developed method was validated as per ICH guidelines. Result: The Kaempferol content in Kaempferol – HSPC Complex was found to be 79.32% and 79.19% at 365 nm and 265 nm. Kaempferol demonstrated good linearity in concentration range of 2 – 12 µg/ml (r2>0.99) at 365 nm and 2 – 14 µg/ml (r 2 >0.99) at 265nm. Precision and mean recoveries were found to be in the range of (% RSD 0.0957 & 0.0580) and (% RSD 0.1461 & 0.0959) and 99.70 % & 91.85 % at 365 nm and at 265 nm. LOD and LOQ were found to be (0.015µg/ml & 0.0191µg/ml) and (0.0457µg/ml & 0.0579µg/ml) respectively. Conclusion: The developed method was found to be simple, specific, economic, reliable, accurate, precise, reproducible and used as a quality control tool for analysis of Kaempferol. Key Words: Freeze drying, HSPC, Kaempferol, Method validation, UV – Visible spectrophotometer.

Polymeric micelle as a nanocarrier for delivery of therapeutic agents: A comprehensive review

Abstract: For selective and effective drug delivery of therapeutic agent nanocarriers are the most effective agents. Micelles are an aggregate of surfactant molecules that dispersed in a liquid colloid. Micelles have a variety of shapes such as spheres, rods, vesicles, tubules, and lamellae. The shape and size of a micelle are a function of the molecular geometry of its surfactant molecules and solution conditions such as surfactant concentration, temperature, pH, and ionic strength. Poly Ethylene Glycol (PEG) is the most commonly used hydrophilic segment of micelles for drug delivery. Besides PEG, other polymers including poly (N-vinyl pyrrolidone) (PVP) and poly (N-isopropyl acrylamide) (pNIPAM) have also been used as hydrophilic portion of micelles. In this review we all discus about the polymeric micelles (PMs) as a nanocarriers for delivery of therapeutic agents. Keywords: Polymeric Micelles, Colloids, Nanocarriers, Drug Delivery, Poly Ethylene Glycol(PEG)

Application of response surface methodology in optimization of paclitaxel liposomes prepared by thin film hydration technique

Abstract: Objective: The present investigation was aimed to optimize the formula of paclitaxel-loaded liposomes (PTL) by using the application of response surface methodology (RSM). Methods: Paclitaxel-loaded liposome (PTL) was optimized by response surface methodology based on two parameters, namely, percent entrapment efficiency (% EE) and percent in vitro drug release at 12 h (% DR). The liposome formula was prepared using 3 2 factorial design, and the selected independent variables were, phospholipid (phospholipon 90G) and cholesterol (CH) concentrations. Nine formulas of paclitaxel-loaded liposome were prepared by thin film hydration technique (THF). The entrapment efficiency, in vitro release studies and drug content, were evaluated using on UV-visible spectrophotometer at λmax-230 nm. The developed PTL formulation vesicle morphology, particle size, polydispersity index (PDI) and zeta potential (ζ) were evaluated by Motic digital microscope and Malvern zetasizer respectively. Results: Using response surface methodology the estimated coefficient values obtained for independent variables in the regression equations, exhibited that the phospholipid (PL90G) and cholesterol (CH) molar concentration was observed to be highly influencing variables in optimizing % EE (86.67±0.67) and % DR (63.49±1.21). In the prediction of % EE and % DR values, the percent relative errors (PRE) was found to be low (–0.290%) and (0.058%) respectively. This suggests that design-developed model was found to be suitable for PTL formulations and thus, validate the model. Conclusion: Experimental results show that the observed responses were in close agreement with the predicted values and this demonstrates the reliability of the RSM in an optimization of % EE and % DR in paclitaxel liposomal (PTL) formulations.

Investigation of effect of phospholipids on physical and functional characterization of paclitaxel liposomes

Abstract: Objective: Aim of the present investigation was to determine the effect of various synthetic grades of phospholipids on paclitaxel liposomes (PTL). Methods: The PTL formulations using various grades of phospholipids were prepared by film hydration method. The prepared PTL formulations were physicochemically characterized by entrapment efficiency (EE, %w/w), vesicular size and particle size distribution. These formulations were also characterized for function parameters such as in vitro release and hemolytic toxicity assay. Results: The synthetic grades of phospholipids significantly influenced PTL formulations. The stoichiometric ratio (1:1) between CH and various synthetic phospholipids was found to be optimized one, from rest of the ratios. The characterization confirmed the formation of PTL. The EE was observed to be high (86.67%) as increasing the ratios between CH and phospholipids but then declined suddenly as further increasing the ratio. The best liposomal formulations showed that the spherical shape was found to be within size ranging from<10 µm, with a higher rate and extent of the release, ~86.22% of paclitaxel from PTL formulation. The results of the hemolytic toxicity study demonstrated that PTL formulations with a ratio (1:1) exhibited a significantly lower hemolytic toxicity (2.70%), compared to all formulations. Conclusion: The result revealed the excellent effect of phospholipids on paclitaxel liposomes. The paclitaxel liposomes prepared with CH: PL90G ratio (1:1) was found to be optimized one. The entrapment efficiency, particle size distribution, in vitro release and hemolytic activity with this ratio shown to be excellent as compared to other ratios.

Fast Dissolving Tablets

Abstract: Difficulty in swallowing is common among all age groups, especially in elderly and pediatrics. Fast dissolving tablets constitute an innovative dosage forms that overcome the problems of swallowing and provide a quick onset of action. Fast-dissolving drug delivery system, in most cases, is a tablet that dissolves or disintegrates in the oral cavity without the need of water or chewing. Fast-dissolving drug delivery system must include substances to mask the taste of the active ingredient. This masked active ingredient is then swallowed by the patient’s saliva along with the soluble and insoluble excipients. Loratadine is antihistaminic drugs which is H1receptor blocker used in the treatment of hay fever and other dermatalogical diseases. In the present study, loratadine fast dissolving tablets were prepared by solid dispersion and using croscarmellose sodium, sodium starch glycolate and polyplasdone XL as super disintegrants. The preformulation study indicated that it is suitable for direct compression. The drug contents of all the tablets were found to be uniform with low standard deviation, indicating efficient mixing and showed quick disintegration and higher dissolution.

Nano-lipid Complex of Rutin: Development, Characterisation and In Vivo Investigation of Hepatoprotective, Antioxidant Activity and Bioavailability Study in Rats

Abstract: The current study was aimed to develop an amphiphilic drug-lipid nano-complex of rutin:egg phosphatidylcholine (EPC) to enhance its poor absorption and bioavailability, and investigated the impact of the complex on hepatoprotective and antioxidant activity. Rutin nano-complexes were prepared by solvent evaporation, salting out and lyophilisation methods and compared for the complex formation. For the selected lyophilisation method, principal solvent DMSO, co-solvent (t-butyl alcohol) and rutin:EPC ratios (1:1, 1:2 and 1:3) were selected after optimisation. The properties of the nano-complexes such as complexation, thermal behaviour, surface morphology, molecular crystallinity, particle size, zeta potential, drug content, solubility, in vitro stability study, in vitro drug release, in vitro and in vivo antioxidant study, in vivo hepatoprotective activity and oral bioavailability/pharmacokinetic studies were investigated. Rutin nano-complexes were developed successfully via the lyophilisation method and found to be in nanometric range. Rutin nano-complexes significantly improved the solubility and in vitro drug release, and kinetic studies confirmed the diffusion-controlled release of the drug from the formulation. The nano-complex showed better antioxidant activity in vitro and exhibited well in vitro stability in different pH media. The in vivo study showed better hepatoprotective activity of the formulation compared to pure rutin at the same dose levels with improved oral bioavailability. Carbon tetrachloride (CCl4)-treated animals (group II) failed to restore the normal levels of serum hepatic marker enzymes and liver antioxidant enzyme compared to the nano-complex-treated animals. The results obtained from solubility, hepatoprotective activity and oral bioavailability studies proved the better efficacy of the nano-complex compared to the pure drug.

The Peroxidative Cleavage of Kaempferol Contributes to the Biosynthesis of the Benzenoid Moiety of Ubiquinone in Plants

Abstract: Land plants possess the unique capacity to derive the benzenoid moiety of the vital respiratory cofactor, ubiquinone (coenzyme Q), from phenylpropanoid metabolism via β-oxidation of p-coumarate to form 4-hydroxybenzoate. Approximately half of the ubiquinone in plants comes from this pathway; the origin of the rest remains enigmatic. In this study, Phe-[Ring-13C6] feeding assays and gene network reconstructions uncovered a connection between the biosynthesis of ubiquinone and that of flavonoids in Arabidopsis (Arabidopsis thaliana). Quantification of ubiquinone in Arabidopsis and tomato (Solanum lycopersicum) mutants in flavonoid biosynthesis pinpointed the corresponding metabolic branch-point as lying between flavanone-3-hydroxylase and flavonoid-3′-hydroxylase. Further isotopic labeling and chemical rescue experiments demonstrated that the B-ring of kaempferol is incorporated into ubiquinone. Moreover, heme-dependent peroxidase activities were shown to be responsible for the cleavage of B-ring of kaempferol to form 4-hydroxybenzoate. By contrast, kaempferol 3-β-d-glucopyranoside, dihydrokaempferol, and naringenin were refractory to peroxidative cleavage. Collectively, these data indicate that kaempferol contributes to the biosynthesis of a vital respiratory cofactor, resulting in an extraordinary metabolic arrangement where a specialized metabolite serves as a precursor for a primary metabolite. Evidence is also provided that the ubiquinone content of tomato fruits can be manipulated via deregulation of flavonoid biosynthesis.