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2.  Comparative In Silico–In Vivo Evaluation of ASGP-R Ligands for Hepatic Targeting of Curcumin Gantrez Nanoparticles 
The AAPS Journal  2013;15(3):696-706.
The present study aims to design hepatic targeted curcumin (CUR) nanoparticles using Gantrez (GZ) as a polymer. Three carbohydrate-based hepatocyte asialoglycoprotein receptor (ASGP-R) ligands were selected for the study, namely kappa carrageenan (KC), arabinogalactan (AG), and pullulan (P). AG and KC are galactose based while P is a glucose-based polymer. CUR-GZ nanoparticles were prepared by nanoprecipitation and anchored with the ligands by nonspecific adsorption onto preformed nanoparticles. The change in zeta potential values confirmed adsorption of the ligands. Docking simulation was evaluated as a tool to predict ligand ASGP-R interactions, using grid-based ligand docking with energies (Glide). Monomers and dimers were used as representative units of polymer for docking analysis. The binding of ASGP-R was validated using d-galactose as monomer. The interaction of the ligands with the receptor was evaluated based on Glide scores and Emodel values, both for monomers and dimers. The data of the docking study based on Glide scores and Emodel values suggested higher affinity of AG and P to the ASGP-R, compared to KC. At 1 h, following intravenous administration of the nanoparticles to rats, the in vivo hepatic accumulation in the order CUR-GZAG > CUR-GZKC > CUR-GZP correlated with the docking data based on Glide scores. However, at the end of 6 h, pullulan exhibited maximum hepatic accumulation and arabinogalactan minimum accumulation (p < 0.05). Nevertheless, as predicted by docking analysis, arabinogalactan and pullulan revealed maximum hepatic accumulation. Docking analysis using dimers as representative stereochemical units of polymers provides a good indication of ligand receptor affinity. Docking analysis provides a useful tool for the preliminary screening of ligands for hepatic targeting.
Electronic supplementary material
The online version of this article (doi:10.1208/s12248-013-9474-6) contains supplementary material, which is available to authorized users.
PMCID: PMC3691424  PMID: 23580183
arabinogalactan; docking; hepatic targeting; kappa carrageenan; pullulan
3.  Buparvaquone loaded solid lipid nanoparticles for targeted delivery in theleriosis 
Buparvaquone (BPQ), a hydroxynaphthoquinone derivative, has been investigated for the treatment of many infections and is recommended as the gold standard for the treatment of theileriosis. Theileriosis, an intramacrophage infection is localized mainly in reticuloendotheileial system (RES) organs. The present study investigates development of solid lipid nanoparticles (SLN) of BPQ for targeted delivery to the RES.
Materials and Methods:
BPQ SLN was prepared using melt method by adding a molten mixture into aqueous Lutrol F68 solution (80°C). Larger batches were prepared up to 6 g of BPQ with GMS: BPQ, 2:1. SLN of designed size were obtained using ultraturrax and high pressure homogenizer. A freeze and thaw study was used to optimize type and concentration of cryoprotectant with Sf: Mean particle size, Si: Initial particle size <1.3. Differential scanning calorimetry (DSC), powder X-ray diffraction (XRD) and scanning electron microscope (SEM) study was performed on optimized formulation. Formulation was investigated for in vitro serum stability, hemolysis and cell uptake study. Pharmacokinetic and biodistribution study was performed in Holtzman rat.
Based on solubility in lipid; glyceryl monostearate (GMS) was selected for preparation of BPQ SLN. Batches of BPQ SLN were optimized for average particle size and entrapment efficiency at <100 mg solid content. A combination of Solutol HS-15 and Lutrol F68 at 2% w/v and greater enabled the desired Sf/Si < 1.3. Differential scanning calorimetry and powder X-ray diffraction revealed decrease in crystallinity of BPQ in BPQ SLN while, scanning electron microscope revealed spherical morphology. BPQ SLN revealed good stability at 4°C and 25°C. Low hemolytic potential (<8%) and in vitro serum stability up to 5 h was observed. Cytotoxicity of SLN to the U937 cell was low. The macrophage cell line revealed high (52%) uptake of BPQ SLN in 1 h suggesting the potential to RES uptake. SLN revealed longer circulation and biodistrbution study confirmed high RES uptake (75%) in RES organs like liver lung spleen etc.
The high RES uptake suggests BPQ SLN as a promising approach for targeted and improved delivery in theileriosis.
PMCID: PMC3895290  PMID: 24459400
Buparavaquone; solid lipid nanoparticles; targeting efficiency; theileriosis
4.  Cellulosic Ethanol Production by Recombinant Cellulolytic Bacteria Harbouring pdc and adh II Genes of Zymomonas mobilis 
The ethanol fermenting genes such as pyruvate decarboxylase (pdc) and alcohol dehydrogenase II (adh II) were cloned from Zymomonas mobilis and transformed into three different cellulolytic bacteria, namely Enterobacter cloacae JV, Proteus mirabilis JV and Erwinia chrysanthemi and their cellulosic ethanol production capability was studied. Recombinant E. cloacae JV was found to produce 4.5% and 3.5% (v/v) ethanol, respectively, when CMC and 4% NaOH pretreated bagasse were used as substrates, whereas recombinant P. mirabilis and E. chrysanthemi with the same substrates could only produce 4%, 3.5%, 1%, and 1.5 % of ethanol, respectively. The recombinant E. cloacae strain produced twofold higher percentage of ethanol than the wild type. The recombinant E. cloacae strain could be improved further by increasing its ethanol tolerance capability through media optimization and also by combining multigene cellulase expression for enhancing ethanol production from various types of lignocellulosic biomass so that it can be used for industrial level ethanol production.
PMCID: PMC3418639  PMID: 22919503
5.  A comparative study of caregiver burden in psychiatric illness and chronic medical illness 
Indian Journal of Psychiatry  2012;54(3):239-243.
Caregivers of individuals suffering from psychiatric illness are at risk of being subjected to mental health consequences such as depression, anxiety and burnout. Community-based studies proved that 18–47% of caregivers land in depression. The caregiver burden can be quantified into objective, subjective and demand burdens. There is paucity of data comparing the caregiver burden of psychiatric patients and that of chronic medical illness patients.
Aims and Objectives:
(1) To compare the caregiver burden in psychiatric illness and chronic medical illness. (2) To study the association of caregiver burden with demographic factors like age, gender, duration of caregiving.
Materials and Methods:
The study included two groups of caregivers, each of 50 members. Group 1 consisted of caregivers of psychiatric patients and group 2 consisted of caregivers of chronic medical illness patients. The Montgomery Borgatta Caregiver Burden scale was used to assess the burden in terms of objective, subjective and demand burdens.
Results and Conclusion:
The caregiver burden scores in the caregivers of psychiatric patients were significantly higher than that of chronic medical illness (P<0.0001). The caregiver burden was found to increase with the duration of illness as well as with the age of caregiver. The caregiver burden in the sample population was less as the objective and demand burden did not cross the reference higher value in the given scale, whereas the emotional impact given by the subjective burden was on higher side.
PMCID: PMC3512360  PMID: 23226847
Burden; caregiver; Illness; psychiatric
6.  Freeze Thaw: A Simple Approach for Prediction of Optimal Cryoprotectant for Freeze Drying 
AAPS PharmSciTech  2010;11(1):304-313.
The present study evaluates freeze thaw as a simple approach for screening the most appropriate cryoprotectant. Freeze–thaw study is based on the principle that an excipient, which protects nanoparticles during the first step of freezing, is likely to be an effective cryoprotectant. Nanoparticles of rifampicin with high entrapment efficiency were prepared by the emulsion-solvent diffusion method using dioctyl sodium sulfosuccinate (AOT) as complexing agent and Gantrez AN-119 as polymer. Freeze–thaw study was carried out using trehalose and fructose as cryoprotectants. The concentration of cryoprotectant, concentration of nanoparticles in the dispersion, and the freezing temperature were varied during the freeze–thaw study. Cryoprotection increased with increase in cryoprotectant concentration. Further, trehalose was superior to fructose at equivalent concentrations and moreover permitted use of more concentrated nanosuspensions for freeze drying. Freezing temperature did not influence the freeze–thaw study. Freeze-dried nanoparticles revealed good redispersibility with a size increase that correlated well with the freeze–thaw study at 20% w/v trehalose and fructose. Transmission electron microscopy revealed round particles with a size ∼400 nm, which correlated with photon correlation spectroscopic measurements. Differential scanning calorimetry and X-ray diffraction suggested amorphization of rifampicin. Fourier transfer infrared spectroscopy could not confirm interaction of drug with AOT. Nanoparticles exhibited sustained release of rifampicin, which followed diffusion kinetics. Nanoparticles of rifampicin were found to be stable for 12 months. The good correlation between freeze thaw and freeze drying suggests freeze–thaw study as a simple and quick approach for screening optimal cryoprotectant for freeze drying.
PMCID: PMC2850490  PMID: 20182826
cryoprotectants; freeze drying; freeze thaw; nanoparticles; rifampicin
7.  Nanoparticles of Polyethylene Sebacate: A New Biodegradable Polymer 
AAPS PharmSciTech  2009;10(3):935-942.
The present study demonstrates feasibility of preparation of nanoparticles using a novel polymer, polyethylene sebacate (PES), and its application in the design of drug-loaded nanocarriers. Silymarin was selected as a model hydrophobic drug for the present study. Two methods of preparation, viz., nanoprecipitation and emulsion solvent diffusion, were evaluated for preparation of nanoparticles. Effect of surfactants polyvinyl alcohol (PVA), lutrol F 68, and Tween 80 on the preparation of blank and silymarin-loaded PES nanoparticles was evaluated. Nanoprecipitation resulted in the formation of nanoparticles with all the surfactants (<450 nm). Increase in surfactant concentration resulted in decrease in entrapment efficiency and particle size except with PVA. The type and concentration of surfactant was critical to achieve low size and adequate drug entrapment. While increase in concentration of PES resulted in larger nanoparticles, inclusion of acetone in the organic phase resulted in particles of smaller size. In case of emulsion solvent diffusion, nanoparticles were obtained only with lutrol F 68 as surfactant and high surfactant concentration. The study revealed nanoprecipitation as a more versatile method for preparation of PES nanoparticles. Scanning electron microscopy studies revealed spherical shape of nanoparticles. Freeze-dried nanoparticles exhibited ease of redispersion, with a marginal increase in size. Differential scanning calorimetry and X-ray diffraction analysis revealed amorphous nature of the drug. The study demonstrates successful design of PES nanoparticles as drug carriers.
PMCID: PMC2802147  PMID: 19629708
biodegradable polymer; emulsion solvent diffusion; nanoparticles; nanoprecipitation; silymarin
Indian Journal of Psychiatry  1998;40(2):192-194.
Mania following or associated with medical and pharmacological conditions is well known. However there are no reports of mania in a case of acute viral hepatitis B infection. This paper describes a manic disorder in a young female with acute viral hepatitis B infection, without any past or family history of psychiatric illness or associated psychosocial stressors.
PMCID: PMC2965845  PMID: 21494469
Organic manic disorder; secondary mania; serum hepatitis; acute viral hepatitis B; icterus; jaundice
9.  Bacteriochlorophyll and Photosynthetic Reaction Centers in Rhizobium Strain BTAi 1 
Applied and Environmental Microbiology  1990;56(11):3445-3449.
Rhizobium strain BTAi 1, which nodulates both stems and roots of Aeschynomene indica L., formed bacteriochlorophyll and photosynthetic reaction centers resembling those of purple photosynthetic bacteria when grown aerobically ex planta under a light-dark cycle. Bacteriochlorophyll formation was not observed under continuous dark or light growth conditions. The amount of pigment formed was similar to that previously found in aerobic photosynthetic bacteria. Stem nodules appear to fix nitrogen photosynthetically, as illumination of A. indica stem nodules with near-infrared light resulted in an enhanced rate of acetylene reduction. Near-infrared light did not enhance acetylene reduction when either A. indica or soybean root nodules were illuminated. The BTAi 1 isolate can be differentiated from members of the family Rhodospirillaceae by several criteria.
PMCID: PMC184979  PMID: 16348349

Results 1-9 (9)