Basavaraj Madhusudhan

Curcuminoids-loaded lipid nanoparticles: novel approach towards malaria treatment.

In the present work, curcuminoids-loaded lipid nanoparticles for parenteral administration were successfully prepared by a nanoemulsion technique employing high-speed homogenizer and ultrasonic probe. For the production of nanoparticles, trimyristin, tristerin and glyceryl monostearate were selected as solid lipids and medium chain triglyceride (MCT) as liquid lipid. Scanning electron microscopy (SEM) revealed the spherical nature of the particles with sizes ranging between 120 and 250 nm measured by photon correlation spectroscopy (PCS). The zeta potential of the particles ranged between -28 and -45 mV depending on the nature of the lipid matrix produced, which also influenced the entrapment efficiency (EE) and drug loading capacity (LC) found to be in the range of 80-94% and 1.62-3.27%, respectively. The LC increased reciprocally on increasing the amount of MCT as confirmed by differential scanning calorimetry (DSC). DSC analyses revealed that increasing imperfections within the lipid matrix allowed for increasing encapsulation parameters. Nanoparticles were further sterilized by filtration process which was found to be superior over autoclaving in preventing thermal degradation of thermo-sensitive curcuminoids. The in vivo pharmacodynamic activity revealed 2-fold increase in antimalarial activity of curcuminoids entrapped in lipid nanoparticles when compared to free curcuminoids at the tested dosage level.

Arthemeter-loaded lipid nanoparticles produced by modified thin-film hydration: Pharmacokinetics, toxicological and in vivo anti-malarial activity

Artemether-loaded lipid nanoparticles (ARM-LNP) composed of 5% (w/v) lipid mass were produced by a modified thin-film hydration method using glyceryl trimyristate (solid lipid) and soybean oil (as liquid lipid in a concentration ranging from 0 to 45% (w/v) with respect to the total lipid mass). The particles were loaded with 10% of the anti-malarial ARM and surface-tailored with a combination of non-ionic, cationic or anionic surfactants. ARM-LNP were further characterized for their mean particle size, zeta potential and encapsulation efficiency, reporting optimized values below 120nm (PI<0.250), -38mV and 97% (w/w), respectively. ARM-LNP composed of 45% soybean oil depicted a spherical-like shape by transmission electron microscopy and a biphasic release profile in phosphate buffer. Haemolytic activity was within the acceptable range (7%) revealing low toxicity risk of LNP for parenteral delivery of ARM. Biocompatibility was confirmed by hepato- and nephrotoxicity analyses. Histopathological analysis showed no significant histological changes in liver and kidney tissues in adult Swiss Albino mice treated with the selected formulations. In vivo anti-malarial activity of ARM was enhanced when formulated as LNP, in comparison to a conventional plain drug solution and to a marketed formulation which are currently in use to treat malaria patients.

Hypocholesterolemic and hepatoprotective effects of flaxseed chutney: Evidence from animal studies

Rats fed with hypercholesterolemic diet showed a significant increase in serum total—cholesterol, liver homogenate total-cholesterol, HDL-cholesterol and changed LDL-cholesterol, and HDL/LDL ratio in comparison to control. Flaxseedchutney (FC) supplemented diet (15%, w/w) was found to be more effective in restoring lipid profile changes in rats fed with cholesterol, (1.0%). The activities of serum marker enzymes glutamate oxaloacetate transminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) were elevated significantly in carbon tetrachloride induced rats. Administration of flaxseedchutney (15%, w/w) resulted in depletion of serum marker enzymes and exhibited recoupment thus showing significant hepatoprotective effect. It was observed that flaxseedchutney supplemented diet could lower the serum cholesterol and as a potential source of antioxidants it could exert protection against hepatotoxic damage induced by carbon tetrachloride (CCl4) in rats.

Effects of flaxseed(Linum usitatissimum) chutney on gamma-glutamyl transpeptidase and micronuclei profile in azoxymethane treated rats

Antioxidant property of flaxseed chutney was evident by decreasing lipid peroxidation (TBARS) and predictor enzyme γ-glutamyl transpeptidase profile and micronuclei formation in azoxymethane treated rats. After 10 weeks, rats fed with either fiber-free basal diet or Antioxidant diet exhibited over sevenfold increase in γ-glutamyl transpeptidase activity and nearly fourfold increase in micronuclei load in comparison to controls (p<0.001). A significant reduction in both γ-glutamyl transpeptidase level (52%) and micronuclei formation (47%) was observed in fiber-free basal diet/Antioxidant diet/flaxseed chutney diet fed rats. Relative to rats fed fiber-free basal diet, the profile of γ-glutamyl transpeptidase and micronuclei load was not significantly altered.

Development and in vitro evaluation of oxytetracycline-loaded PMMA nanoparticles for oral delivery against anaplasmosis

Poly-methyl methacrylate (PMMA) polymer with remarkable properties and merits are being preferred in various biomedical applications due to its biocompatibility, non-toxicity and cost effectiveness. In this investigation, oxytetracycline-loaded PMMA nanoparticles were prepared using nano-precipitation method for the treatment of anaplasmosis. The prepared nanoparticles were characterised using dynamic light scattering (DLS), atomic force microscopy (AFM), differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. The mean average diameter of the nanoparticles ranged between 190-240 nm and zeta potential was found to be -19 mV. The drug loading capacity and entrapment efficiency of nanoparticles was found varied between 33.7-62.2% and 40.5-60.0%. The in vitro drug release profile exhibited a biphasic phenomenon indicating controlled drug release. The uptake of coumarin-6(C-6)-loaded PMMA nanoparticles in Plasmodium falciparum (Pf3D7) culture model was studied. The preferential uptake of C-6-loaded nanoparticles by the Plasmodium infected erythrocytes in comparison with the uninfected erythrocytes was observed under fluorescence microscopy. These findings suggest that oxytetracycline-loaded PMMA nanoparticles were found to be an effective oral delivery vehicle and an alternative pharmaceutical formulation in anaplasmosis treatment, too.