Current Nanomedicine - Volume 9, Issue 2, 2019
Volume 9, Issue 2, 2019
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Biomedical Nano Tools: A Potential New Paradigm for Immunoassays and Immune Detection
Authors: Nitai Debnath and Sumistha DasImmunoassays are microwell and solid phase based antigen-antibody (Ag/Ab) interactions majorly dependent on immune complex or lattice formation. Most of these assays are aimed at the detection of very minute amount of antigen or antibody. Such biochemical reactions are bound to identify not only the target biomolecule (immunoassay) but also clinically important pathogens (immune detection) because of their remarkable simplicity, specificity and sensitivity. But the existing technology suffers from certain difficulties like affinity and avidity of antigen and antibody, vigorous washing methods, chances of false positive interactions, appropriate probe selection and dependence on carcinogenic (as substrate) or hazardous radioisotopes. An urgent need is being felt to ensure more specific, powerful and versatile platform for robust detection of immune reactions. In this scenario, application of nanomaterials in immunoassays may pave a new horizon for immune based detection. Optically active nanomaterial dependent detection reduces the chance of false positive results as well as chromogen or radioisotope dependence and time and cost incurred for those. In this perspective, the immense potential of biomedical nanodevices in immunoassays is summarized in this article. Moreover, application of gold nanoparticles in all types of biosensor (electrochemical, optical, surface enhanced Raman scattering based and engineered) is also discussed as a specific tool in nano immunosensors.
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Hydrophobic Modification of Copper Nanospheres for Incorporation into Poloxamer Micelles, Aggregated Micellar Nanocages and Supramolecular Assemblies
Authors: Yunlong Xu, Kaspars Melkis, Chinn T. Sia and Dipak K. SarkerBackground: Polymer nanogels are increasingly used for the encapsulation of nano-solids and quantum dots such as in advanced forms of drug and therapeutic isotope delivery. Objective: Unlike ex vivo application of systems in vivo application and internalization are likely to suffer from aspects of failure to ensure safety and biocompatibility. Biocompatible hydrophilic poloxamer (Pluronic F108 and F68) micelles were studied by light scattering and tensiometry. Methods: The micelles of nano-gels are synthetic heteropolymer aggregates, which are used to encapsulate drugs but in this study chemically-modified (hydrophobized) copper nano-spheres, for the purposes of demonstration for further application and medical use. Copper benzoate nano-particles (CuBzNPs) were produced by maceration and subsequently stabilized in Pluronic F108 solution was added at different concentrations. Results: The resulting particle size increase was studied by dynamic light scattering. Moderate size increase was observed at low Pluronic F108 concentrations, which indicated successful coating, but at higher F108 concentrations large size agglomerates formed. Coated copper benzoate nano-particles (CuBzNPs) were fabricated as a proof-of-principle and as a substitute for bare metal nano-particles (MNs), which were not successfully entrained in the poloxamer nano-gel. As part of the synthesis copper benzoate (CuBz) beads and their characterization through contact angle measurements were performed. Conclusion: Micelles sizes of 4 nm for F68 Pluronic at equilibrium surface tensions of 36 mNm-1 were captured in weak, 1.25 to 2.0 Pas pseudoplastic gels fabricated from hydroxypropylmethylcellulose (HPMC).
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Enhanced Release Kinetics and Stability of Resveratrol Loaded Self Nanoemulsifying Delivery Systems Developed using Experimental Design
Authors: Monika Sharma, Rajeev Garg and Satish SardanaBackground: Resveratrol is a member of the stilbene family emerged as a leading candidate for improving healthspan through potentially slowing the aging process and preventing chronic diseases. A number of institutions and scientists specialized in this field across the world are working to develop a promising Self Emulsifying formulation to enhance bioavailability of hydrophobic resveratrol using oil. Objectives: The objective of the current study is to develop self-nano emulsifying drug delivery systems using long-chain triglycerides of resveratrol to enhance solubility, stability, release kinetics and to overcome low bioavailability. Methods: Solubility studies performed in different lipids, surfactants and cosurfactants. Phase diagrams constructed to select the areas of nanoemulsion. SNEDDS formulation was optimized using 33 central composite design considering lipid (X1), surfactant (X2) and co-surfactant (X3) as critical variables, optimized formulation was located using overlay plot. Results: The nanometer size and high values of zeta potential depicted non-coalescent nature of SNEDDS. The resulted SNEDDS formulation had improved in vitro release followed by Hixson Crowell model with higher regression R2value 0. 929. Thermodynamic stability studies ascertained stable formulation. Mean droplet size in selected nanocarrier was found to be 83.29 nm. The nanocarriers subjected to 2-8°C (45% RH), 25-30°C (60% RH) and 45-50°C (75% RH) in glass vials exhibited no significant changes in 3 months. Conclusion: The novel approach was developed by selecting optimum blends of lipids, surfactants and cosurfactant using central composite design. This study not only offers a good example of augmenting bioavailability of resveratrol but will also provide a promising oral formulation for clinical application.
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Green Synthesis of Gold Nanoparticles Using Different Leaf Extracts of Ocimum gratissimum Linn for Anti-tubercular Activity
Authors: Arti Gupta, Sonia Pandey, Bharat Variya, Shailesh Shah and Jitendra S. YadavBackground: Tuberculosis is a greatest threat to human health. It requires urgent need to seek new devise alternate strategies and ant-tubercular compounds. In the present scenario, Nonmaterias, have opened new avenues in medicine, diagnosis and therapeutics. Objective: In view of this, the current study aims to synthesize gold nanoparticles and determine its efficacy to inhibit Mycobacterium tuberculosis. Methods: Gold nanoparticles (GNPs) synthesized from medicinal plant, such as Ocimum gratissimum linn, were tested against Mycobacterium tuberculosis (H37RV strain). Gold nanoparticles were characterized by UV-Vis spectrophotometer, FTIR, SEM and TEM. TEM results revealed that the GNPs were found spherical in structure and around 10-25 nm in diameter. UV-Vis spectroscopy exhibited an absorption peak at 348 nm. Fourier transform infra-red spectroscopy showed the GNPs have coated with phytoconstituents (terpenoids) that indicate the role of bio-molecules responsible for efficient stabilization and capping of the gold nanoparticles. In vitro model was designed to determine minimum inhibitory concentration (MIC) of each sample by Lowenstein Jensen (LJ) slope method. Results: The results showed that the presence of ursolic acid in ethanolic and hydroalcoholic extracts was found to be 2.89% and 1.97%, respectively. GNPs of ethanolic and hydroalcoholic exhibited anti-tubercular activity, with MIC 2.5 μg/ml and 20 μg/ml, respectively. While ethanolic and hydroalcoholic extracts showed such activity at concentrations 50 μg/ml and 75 μg/ml, respectively. Conclusion: GNPs synthesized from ethanolic extract showed profound efficiency to kill mycobacteria. As in this method no chemical reagents were used, the synthesized gold nanoparticles have potential for biological applications. There is an urgent need to further development of nano-antibiotic for tuberculosis.
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Influence of Lipid’s Main Transition Temperature on the Stability of Chimeric Liposomal Systems
Background: The incorporation of polymeric components into liposomes promotes structural rearrangement of the lipid bilayers that could affect their properties and their behavior. Therefore, by mixing phospholipids with polymeric compounds the, socalled chimeric liposomal nanosystems are produced and could be advantageous, compared with conventional (e.g. composed of pure phospholipids) liposomal nanostructures. Objective: In this work, we used lipids with different main transition temperature (Tm) i.e 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC, Tm=55°C), L-α-phosphatidylcholine, hydrogenated (Soy) (HSPC, Tm=52 °C) and egg phosphatidylcholine (EggPC, Tm=23 °C) and we studied and compared the physicochemical characteristics and the stability of conventional with that of chimeric liposomes. Methods: Thin-film hydration method (TFH) was used as the preparation protocol for all systems. Dynamic and electrophoretic light scattering (DLS and ELS) were utilized in order to elucidate the physicochemical characteristics of all systems. All liposomal systems exhibited sizes below 100nm while the ζ-potential was around zero, indicating the absence of surface charge. Results: The results revealed that the Tm of each phospholipid influences the biophysical behavior of the lipidic membrane, which contributes to the physicochemical characteristics and affects the physical stability of the liposomal nanosystems. The nature and physicochemical properties of each phospholipid seem to play a key role, regarding the structural characteristics and the formation process of the liposomal nanosystems. Conclusion: Comparing the physicochemical properties of the conventional liposomes with those of the chimeric liposomal systems, we conclude that the complexity of the latter, due to the incorporation of the polymeric guest into the lipidic bilayer, revealed new properties, which correspond to increased physical stability.
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Shaping and Cellular Uptake of Folic Acid Coated Gold and Magnetite Nanoparticles
Authors: Ahmed A.G. El-Shahawy, Gamal Elghnam and Alsayed A.M. AlsherbiniBackground: Gold and Iron Oxide nanoparticles NPs play as nanocarriers for a specific drug delivery and contrast agents. Intercellular uptake of these nanoparticles and targeting to individual cell and sub-cellular compartment is essential. Objective: The aim of the current study is to evaluate the intracellular uptake of these NPs to specific tumor cells in vitro conjugated with folic acid with a goal of enhancing the efficiency of specific targeting to tumor cells. Methods: We synthesized the nanoparticles by a chemical method and characterized by UV-Visible, FTIR, XRD, and TEM. Results & Conclusion: The results revealed the conjugation of Gold and Iron Oxide nanoparticles with folic acid increased the intercellular uptake with high percent compared to non- conjugated nanoparticles.
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Double PEGylation Significantly Improves Pharmacokinetic Properties of Irinotecan Containing Nanoparticles in a Zebrafish Model
Background: Plasma pharmacokinetic (PK) properties of oral or injectable drugs dictate whether the drug is clinically viable or not. Poor PK properties often result in termination of the development of the drug. Optimizing PK properties of drugs is a major challenge in the pharmaceutical industry. Ideally, sufficient circulating time of the drug in the plasma is required, so that it has adequate opportunity to reach the target tissue. Methods: We have used irinotecan, a known drug with poor PK properties, as a prototype to apply our idea of improving PK in plasma by PEGylation. We compared the PK profile of free irinotecan, irinotecan packaged in nanoparticles (NPs) with single polyethylene glycol (PEG) layer and irinotecan packaged in NPs with double PEG layer. PK properties of these formulations were compared in a zebrafish model when given intraperitoneally. Results: Dramatic differences in the PK properties of the three formulations were observed. The AUC, Cmax and T1/2 of irinotecan in each of these formulations differed from each other significantly. Approx. 4.5 - fold higher peak concentration (Cmax) and ~3 - fold higher exposure (AUC0-t) were observed for double PEGylated NPs as compared to free irinotecan and single PEGylated NPs. Conclusion: In summary, our data suggest that double PEGylation of NPs could be a very effective way to improve PK properties of drugs such as irinotecan.
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