Indranil Banerjee

Folate receptor targeted, carboxymethyl chitosan functionalized iron oxide nanoparticles: a novel ultradispersed nanoconjugates for bimodal imaging

This article delineates the design and synthesis of a novel, bio-functionalized, magneto-fluorescent multifunctional nanoparticles suitable for cancer-specific targeting, detection and imaging. Biocompatible, hydrophilic, magneto-fluorescent nanoparticles with surface-pendant amine, carboxyl and aldehyde groups were designed using o-carboxymethyl chitosan (OCMC). The free amine groups of OCMC stabilized magnetite nanoparticles on the surface allow for the covalent attachment of a fluorescent dye such as rhodamine isothiocyanate (RITC) with the aim to develop a magneto-fluorescent nanoprobe for optical imaging. In order to impart specific cancer cell targeting properties, folic acid and its aminated derivative was conjugated onto these magneto-fluorescent nanoparticles using different pendant groups (-NH(2), -COOH, -CHO). These newly synthesized iron-oxide folate nanoconjugates (FA-RITC-OCMC-SPIONs) showed excellent dispersibility, biocompatibility and good hydrodynamic sizes under physiological conditions which were extensively studied by a variety of complementary techniques. The cellular internalization efficacy of these folate-targeted and its non-targeted counterparts were studied using a folate-overexpressed (HeLa) and a normal (L929 fibroblast) cells by fluorescence microscopy and magnetically activated cell sorting (MACS). Cell-uptake behaviors of nanoparticles clearly demonstrate that cancer cells over-expressing the human folate receptor internalized a higher level of these nanoparticle-folate conjugates than normal cells. These folate targeted nanoparticles possess specific magnetic properties in the presence of an external magnetic field and the potential of these nanoconjugates as T(2)-weighted negative contrast MR imaging agent were evaluated in folate-overexpressed HeLa and normal L929 fibroblast cells.

Association of gene polymorphism with genetic susceptibility to stroke in Asian populations: a meta-analysis

AbstractStroke is a heterogeneous multifactorial disease and is thought to have a polygenic basis. Case-control studies on gene sequence variations have identified a number of potential genetic predisposition factors, but due to the conflicting results, uncertainty remains on the effect of these polymorphisms on risk for the development of stroke. To qualitatively and quantitatively assess the risk associated with different gene polymorphisms for stroke in Asian populations, we comprehensively searched and identified all the studies of association. Clinically overt case-control studies were selected only if neuroimaging had been used as the confirmatory measure for diagnosis of stroke. We performed a meta-analysis of the three most investigated genes, viz., methylenetetrahydrofolate reductase (MTHFR), apolipoprotein E (ApoE) and angiotensin-converting enzyme (ACE). Statistically significant association with stroke were identified for C677T polymorphism of MTHFR [random effects odds ratio (OR) = 1.47, 95% confidence interval (95% CI) 1.19, 1.82; P = 0.0004] and marginally significant association was detected with allele ε 4 of ApoE (random effects OR = 1.47, 95% CI 1.00, 2.15; P = 0.049). The sensitivity analysis (exclusion of studies with controls not in Hardy-Weinberg equilibrium) revealed a significant association of stroke with the MTHFR C677T and ApoE ɛ 4 alleles but showed no association with ACE gene insertion/deletion polymorphism.

Inflammatory system gene polymorphism and the risk of stroke: A case–control study in an Indian population

Sequence variations in genes involved in inflammation system are known to contribute to the risk of cardiovascular diseases (CVD) including stroke. In this study, we performed a genetic association study on the single nucleotide polymorphisms (SNPs) present in the genes CD14 (-159 C/T), TNFalpha (-308 G/A), IL-1alpha (-889 C/T), IL-6 (-174 G/C), PSMA6 (-8 C/G), and PDE4D (SNP83 T/C, respectively) in order to discern their possible role in the susceptibility to stroke in a North Indian population. These SNPs were previously found to be associated with CVD through their contribution to inflammation. A case-control design was used to examine 176 stroke patients (112 ischemic and 64 hemorrhagic stroke patients) and 212 unrelated healthy control individuals. After adjustment for the confounding risk factors, the IL-1alpha -889 T allele carriers (TT+CT) were found to be strongly associated with both forms of stroke (OR=2.56; 95% CI=1.53-4.29; P=0.0004). The CC genotype of PDE4D was found to be associated only with ischemic stroke (OR=2.02; 95% CI=1.08-3.76; P=0.03). None of the variants tested for the CD14, TNFalpha, IL-6, and PSMA6 genes found to confer risk for stroke in the study population. In conclusion, the -889 C/T and SNP83 T/C SNPs of the IL-1alpha and PDE4D genes, respectively, appear to be genetic risk factors for stroke in our study population.

Calcium alginate-carboxymethyl cellulose beads for colon-targeted drug delivery

The present study delineates preparation, characterization and application of calcium alginate (CA)-carboxymethyl cellulose (CMC) beads for colon-specific oral drug delivery. Here, we exploited pH responsive swelling, mucoadhesivity and colonic microflora-catered biodegradability of the formulations for colon-specific drug delivery. The CA-CMC beads were prepared by ionic gelation method and its physicochemical characterization was done by SEM, XRD, EDAX, DSC and texture analyzer. The swelling and mucoadhesivity of the beads was found higher at the simulated colonic environment. Variation was more prominent in compositions with lower CMC concentrations. CA-CMC formulations degraded slowly in simulated colonic fluid, however the degradation rate increased drastically in the presence of colonic microflora. In vitro release study of anticancer drug 5-fluorouracil (5-FU) showed a release (>90%) in the presence of colonic enzymes. A critical analysis of drug release profile along with FRAP (fluorescence recovery after photobleaching) study revealed that the presence of CMC in the formulation retarded the release rate of 5-FU. 5-FU-loaded formulations were tested against colon adenocarcinoma cells (HT-29). Cytotoxicity data, nuclear condensation-fragmentation and apoptosis analysis (by flow cytometry) together confirmed the therapeutic potential of the CA-CMC formulations. In conclusion, CA-CMC beads can be used for colon-specific drug delivery.

Organogels as Matrices for Controlled Drug Delivery: A Review on the Current State

Over the last two decades, organogels have found tremendous use in the pharmaceutical, food, and cosmetics industries with notable developments as drug delivery matrices and trans and saturated fat replacers in processed foods. The functionality of organogels benefits from their ease of preparation, cost effectiveness, and ability to contain both hydrophilic and lipophilic constituents. This review provides thorough insight into different organogelators, their mechanisms of organogel formation, various characterization techniques and their biocompatibility when administered in vivo. Finally, a special treatise is given on the applications of organogels as controlled drug delivery vehicles for topical, dermal/transdermal, parenteral, oral, and nasal routes. In situ forming organogels and their potential for tailored release of incorporated active ingredients are also discussed.

Chemical Synthesis, Characterization, and Biocompatibility Study of Hydroxyapatite/Chitosan Phosphate Nanocomposite for Bone Tissue Engineering Applications

A novel bioanalogue hydroxyapatite (HAp)/chitosan phosphate (CSP) nanocomposite has been synthesized by a solution-based chemical methodology with varying HAp contents from 10 to 60% (w/w). The interfacial bonding interaction between HAp and CSP has been investigated through Fourier transform infrared absorption spectra (FTIR) and x-ray diffraction (XRD). The surface morphology of the composite and the homogeneous dispersion of nanoparticles in the polymer matrix have been investigated through scanning electron microscopy (SEM) and transmission electron microscopy (TEM), respectively. The mechanical properties of the composite are found to be improved significantly with increase in nanoparticle contents. Cytotoxicity test using murine L929 fibroblast confirms that the nanocomposite is cytocompatible. Primary murine osteoblast cell culture study proves that the nanocomposite is osteocompatible and highly in vitro osteogenic. The use of CSP promotes the homogeneous distribution of particles in the polymer matrix through its pendant phosphate groups along with particle-polymer interfacial interactions. The prepared HAp/CSP nanocomposite with uniform microstructure may be used in bone tissue engineering applications.

Sustained release of antibiotic from polyurethane coated implant materials.

Implant associated infections are of increasing importance. To minimize the risks of implant-associated infections recent biomedical strategies have led to the modification of the medical device surfaces. The modifications are in the terms of increasing surface biocompatibility and decreasing bacterial adherence, which can be achieved by applying a coating of biocompatible polymer onto the said surfaces. Entrapping anti-infective agents in a polymer matrix provides an approach to kill bacteria and combat the possibility of any residual infection. We have prepared a biodegradable polyester urethane coat for implant materials, which have the property to accommodate antibiotics within itself. These polyurethane coating materials were characterized by FTIR spectroscopy, swelling property in SBF, gravimetric analysis, drug release, and biocompatibility study. Drug release rates, bacterial colonization and morphological features were also evaluated to predict and understand the antimicrobial activity of these delivery systems. Drug release characteristics were investigated and the physico-chemical mechanisms of the delivery were discussed. Results suggest that the polyester urethane can be used as an implant coating material and can be used as a matrix for the sustained delivery of anti-infective agent.

Guar gum and sesame oil based novel bigels for controlled drug delivery

Bigels are novel semi-solid formulations which have been drawing attention of many research scientists due to their numerous advantages over the conventional gels. The objective of this study was to develop and characterize novel bigels by mixing guar gum hydrogel and sorbitan monostearate-sesame oil based organogel for controlled drug delivery applications. The confocal microscopy suggested the existence of both aqueous and oil phases together as bigel. Micro-scale deformation (viscometric) analysis in conjugation with macro-scale deformation studies suggested shear-thinning and viscoelastic nature of the bigels. Thermal study suggested an increase in thermal stability with the increase in organogel proportion in the bigels. The developed bigels were biocompatible in nature. The in vitro drug release study showed that the release of ciprofloxacin (lipophilic drug) increased with a decrease in the organogel content. Further analysis showed that the drug release from all the bigels followed zero order diffusion kinetics which is desirable for a controlled release system. The drug loaded gels showed good antimicrobial efficiency against Bacillus subtilis. In conclusion, the developed bigels may be tried as matrices for topical drug delivery.

PLGA Microspheres Incorporated Gelatin Scaffold: Microspheres Modulate Scaffold Properties

Freeze drying is one of the popular methods of fabrication for poly(lactide-co-glycolide) (PLGA) microspheres incorporated polymer scaffolds. However, the consequence of microspheres incorporation on physical and biological properties of scaffold has not been studied yet. In this study, attempt has been made to characterize the effect of PLGA microsphere incorporation on the physical properties of freeze-dried gelatin scaffold and its influence on cytocompatibility. Scaffolds loaded with varying amount of PLGA microspheres (10%, 1%, 0.1% w/w) were subjected to microarchitecture analysis, swelling, porosity, mechanical properties, biodegradation, cell adhesion, and cell proliferation studies. Results revealed that an increase in percentage loading of microspheres reduced the pore size and uniformity of the pore structure. Moreover, loading of PLGA microspheres up to 1% w/w significantly increased porosity, swelling, and mechanical properties of the scaffold but variations were not proportional for 10% w/w loading. Results also showed that PLGA microspheres have no significant effect on cell adhesion but influenced the growth kinetics.

Preparation and characterization of novel carbopol based bigels for topical delivery of metronidazole for the treatment of bacterial vaginosis

The current study reports the development of bigels using sorbitan monostearate-sesame oil organogel and carbopol 934 hydrogel. The microstructures and physicochemical properties were investigated by microscopy, viscosity measurement, mechanical analysis and differential scanning calorimetry analysis. Fluorescence microscopy confirmed the formation of oil-in-water type of emulsion gel. There was an increase in the strength of the bigels as the proportion of the organogel was increased in the bigels. The developed bigels showed shear-thinning flow behavior. The stress relaxation study suggested viscoelastic nature of the bigels. The developed bigels were biocompatible. Metronidazole, drug of choice for the treatment of bacterial vaginosis, loaded bigels showed diffusion-mediated drug release. The drug loaded gels showed good antimicrobial efficiency against Escherichia coli. In gist, the developed bigels may be used as delivery vehicles for the vaginal delivery of the drugs.