Dattatri Nagesha

Nanoporous inorganic membranes or coatings for sustained drug delivery in implantable devices

The characteristics of nanoporous inorganic coatings on implants or on implantable devices are reviewed. The commonly used nanoporous materials, such as aluminum oxide (Al(2)O(3)), titanium oxide (TiO(2)) and porous silicon are highlighted with illustrative examples. The critical issues for sustained release systems are examined and the elution profiles of nanoporous coatings are discussed. The available data shows that these systems can be used effectively for sustained release applications. They satisfy the basic biocompatibility tests, meet the requirements of drug loading and sustained release profiles extending to several weeks and also are compatible with current implant technologies. Nanoporous inorganic coatings are well suited to provide improved efficacy and integration of implants in a variety of therapeutic situations.

Toxicity of CdSe Nanoparticles in Caco-2 Cell Cultures

BackgroundPotential routes of nanomaterial exposure include inhalation, dermal contact, and ingestion. Toxicology of inhalation of ultra-fine particles has been extensively studied; however, risks of nanomaterial exposure via ingestion are currently almost unknown. Using enterocyte-like Caco-2 cells as a small intestine epithelial model, the possible toxicity of CdSe quantum dot (QD) exposure via ingestion was investigated. Effect of simulated gastric fluid treatment on CdSe QD cytotoxicity was also studied.ResultsCommercially available CdSe QDs, which have a ZnS shell and poly-ethylene glycol (PEG) coating, and in-house prepared surfactant coated CdSe QDs were dosed to Caco-2 cells. Cell viability and attachment were studied after 24 hours of incubation. It was found that cytotoxicity of CdSe QDs was modulated by surface coating, as PEG coated CdSe QDs had less of an effect on Caco-2 cell viability and attachment. Acid treatment increased the toxicity of PEG coated QDs, most likely due to damage or removal of the surface coating and exposure of CdSe core material. Incubation with un-dialyzed in-house prepared CdSe QD preparations, which contained an excess amount of free Cd2+, resulted in dramatically reduced cell viability.ConclusionExposure to CdSe QDs resulted in cultured intestinal cell detachment and death; cytotoxicity depended largely, however, on the QD coating and treatment (e.g. acid treatment, dialysis). Experimental results generally indicated that Caco-2 cell viability correlated with concentration of free Cd2+ ions present in cell culture medium. Exposure to low (gastric) pH affected cytotoxicity of CdSe QDs, indicating that route of exposure may be an important factor in QD cytotoxicity.

In Vitro Evaluation of Theranostic Polymeric Micelles for Imaging and Drug Delivery in Cancer

For the past decade engineered nanoplatforms have seen a momentous progress in developing a multimodal theranostic formulation which can be simultaneously used for imaging and therapy. In this report we describe the synthesis and application of theranostic phospholipid based polymeric micelles for optical fluorescence imaging and controlled drug delivery. CdSe quantum dots (QDs) and anti-cancer drug, doxorubicin (Dox), were co-encapsulated into the hydrophobic core of the micelles. The micelles are characterized using optical spectroscopy for characteristic absorbance and fluorescence features of QDs and Dox. TEM and DLS studies yielded a size of <50 nm for the micellar formulations with very narrow size distribution. A sustained release of the drug was observed from the co-encapsulated micellar formulation. In vitro optical fluorescence imaging and cytotoxicity studies with HeLa cell line demonstrated the potential of these micellar systems as efficient optical imaging and therapeutic probes.

Functionalization-induced improvement in magnetic properties of Fe3O4 nanoparticles for biomedical applications

Fe3O4 were synthesized nanoparticles by thermal decomposition method with oleic acid as the surfactant, and to make them suitable for aqueous environments, dopamine ligand exchange was carried out on the particles. The nanoparticle size and phase was quantified by transmission electron microscopy (TEM) and x-ray diffraction (XRD), respectively. Superconducting quantum interference device magnetometry confirmed superparamagnetic behavior in both nanoparticles. A surprising and significant increase in the remanence MR, saturation magnetization MS, and blocking temperature TB of the particles was found after dopamine functionalization, even though TEM and XRD studies revealed no change in the particles’ size and/or structure. The results are consistent with an increase in the magnetic size of the nanoparticle core induced by the dopamine ligand exchange process. These effects are tentatively attributed to surface bonding effects that alter the canted magnetic state of the Fe3O4 nanoparticles.

Monitoring of magnetic targeting to tumor vasculature through MRI and biodistribution

AIMS The development of noninvasive imaging techniques for the assessment of cancer treatment is rapidly becoming highly important. The aim of the present study is to show that magnetic cationic liposomes (MCLs), incorporating superparamagnetic iron oxide nanoparticles (SPIONs), are a versatile theranostic nanoplatform for enhanced drug delivery and monitoring of cancer treatment. MATERIALS & METHODS MCLs (with incorporated high SPION cargo) were administered to a severe combined immunodeficiency mouse with metastatic (B16-F10) melanoma grown in the right flank. Pre- and post-injection magnetic resonance (MR) images were used to assess response to magnetic targeting effects. Biodistribution studies were conducted by ¹¹¹In-labeled MCLs and the amount of radioactivity recovered was used to confirm the effect of targeting for intratumoral administrations. RESULTS We have shown that tumor signal intensities in T₂-weighted MR images decreased by an average of 20 ± 5% and T₂* relaxation times decreased by 14 ± 7 ms 24 h after intravenous administration of our MCL formulation. This compares to an average decrease in tumor signal intensity of 57 ± 12% and a T₂* relaxation time decrease of 27 ± 8 ms after the same time period with the aid of magnetic guidance. CONCLUSION MR and biodistribution analysis clearly show the efficacy of MCLs as MRI contrast agents, prove the use of magnetic guidance, and demonstrate the potential of MCLs as agents for imaging, guidance and therapeutic delivery.

Sustained drug release from non-eroding nanoporous templates.

Inthosesituationsitisnecessarytohaveareservoirthatdoesnotdegradeorerode.Non-eroding nanoporousoxide coatingsofferanattractivealternativeplatformsincetheyarenonerodibleandtheir nanofeatures allow control of the elution profile.Herein, we present the results for the release of a modeldrug,doxorubicin(Dox),fromdifferentnon-erodingnanopor-ous coatings. Detailed studies of drug release from theseplatforms in the form of anodic aluminum oxide (AAO) andanodictitaniumoxide(ATO)werecarriedout.Therearemanyapproaches to sputter metals, such as titanium and aluminum,on different materials and to anodize them afterwards,

Phospholipid-modified polyethylenimine-based nanopreparations for siRNA–mediated gene silencing: Implications for transfection and the role of lipid components

UNLABELLED The clinical application of gene silencing mediated by small interfering RNA (siRNA) has been limited by the lack of efficient and safe carriers. Phospholipid modification of low molecular weight polyethylenimine (PEI 1.8 kDa) dramatically increased its gene down-regulation capacity while keeping cytotoxicity levels low. The silencing efficacy was highly dependent on the nature of the lipid grafted to PEI and the polymer/siRNA ratio employed. Phosphoethanolamine (DOPE and DPPE) and phosphocholine (PC) conjugation did not change the physicochemical properties and siRNA binding capacity of PEI complexes but had a large impact on their transfection and ability to down-regulate Green Fluorescent Protein (GFP) expression (60%, 30% and 5% decrease of GFP expression respectively). We found that the micelle-forming structure of DOPE and DPPE-PEI dramatically changed PEIs interaction with cell membranes and played a key role in promoting PEI 1.8 kDa transfection, completely ineffective in the absence of the lipid modification. FROM THE CLINICAL EDITOR While siRNA-based gene silencing methods could have numerous clinical applications, efficient delivery remains a major challenge. This team reports that DOPE-PEI and DPPE-PEI based micelle-forming nanostructures may be able to provide an efficient vector for siRNA transfection.

High-throughput assembly of nanoelements in nanoporous alumina templates

The authors demonstrate a nanofabrication method utilizing nanoporous alumina templates which involves directed three dimensional assembly of nanoparticles inside the pores by means of an electrophoretic technique. In their demonstration, they have assembled polystyrene nanobeads with diameter of 50nm inside nanopore arrays of height of 250nm and diameter of 80nm. Such a technique is particularly useful for large-scale, rapid assembly of nanoelements for potential device applications.

Integrity of 111In-radiolabeled superparamagnetic iron oxide nanoparticles in the mouse☆

INTRODUCTION Iron-oxide nanoparticles can act as contrast agents in magnetic resonance imaging (MRI), while radiolabeling the same platform with nuclear medicine isotopes allows imaging with positron emission tomography (PET) or single-photon emission computed tomography (SPECT), modalities that offer better quantification. For successful translation of these multifunctional imaging platforms to clinical use, it is imperative to evaluate the degree to which the association between radioactive label and iron oxide core remains intact in vivo. METHODS We prepared iron oxide nanoparticles stabilized by oleic acid and phospholipids which were further radiolabeled with (59)Fe, (14)C-oleic acid, and (111)In. RESULTS Mouse biodistributions showed (111)In preferentially localized in reticuloendothelial organs, liver, spleen and bone. However, there were greater levels of (59)Fe than (111)In in liver and spleen, but lower levels of (14)C. CONCLUSIONS While there is some degree of dissociation between the (111)In labeled component of the nanoparticle and the iron oxide core, there is extensive dissociation of the oleic acid component.

Radiosensitizer-eluting nanocoatings on gold fiducials for biological in-situ image-guided radio therapy (BIS-IGRT).

Image-guided radiation treatments (IGRT) routinely utilize radio-opaque implantable devices, such as fiducials or brachytherapy spacers, for improved spatial accuracy. The therapeutic efficiency of IGRT can be further enhanced by biological in situ dose painting (BIS-IGRT) of radiosensitizers through localized delivery within the tumor using gold fiducial markers that have been coated with nanoporous polymer matrices loaded with nanoparticles (NPs). In this work, two approaches were studied: (i) a free drug release system consisting of Doxorubicin (Dox), a hydrophilic drug, loaded into a non-degradable polymer poly(methyl methacrylate) (PMMA) coating and (ii) poly(d,l-lactic-co-glycolic acid) (PLGA) NPs loaded with fluorescent Coumarin-6, serving as a model for a hydrophobic drug, in a biodegradable chitosan matrix. Temporal release kinetics measurements in buffer were carried out using fluorescence spectroscopy. In the first case of free Dox release, an initial release within the first few hours was followed by a sustained release over the course of the next 3 months. In the second platform, release of NPs and the free drug was controlled by the degradation rate of the chitosan matrix and PLGA. The results show that dosage and rate of release of these radiosensitizers coated on gold fiducials for IGRT can be precisely tailored to achieve the desired release profile for radiation therapy of cancer.