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      Investigation of Size and Morphology of Chitosan Nanoparticles Used in Drug Delivery System Employing Chemometric Technique

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          Abstract

          The polymeric nanoparticles are prepared from biocompatible polymers in size between 10-1000 nm. Chitosan is a biocompatible polymer that - can be utilized as drug delivery systems. In this study, chitosan nanoparticles were synthesized using an optimized spontaneous emulsification method. Determining particle size and morphology are two critical parameters in nanotechnology. The aim of this study is to introduce methodology based on relation between particle size and diffuse reflectance infrared fourier transform (DRIFT) spectroscopy technique. Partial least squares (PLS) technique was used to estimate the average particle size based on DRIFT spectra. Forty two different chitosan nanoparticle samples with different particle sizes were analyzed using DRIFT spectrometry and the obtained data were processed by PLS. Results obtained from the real samples were compared to those obtained using field emission scanning electron microscope(FE-SEM) as a reference method. It was observed that PLS could correctly predict the average particle size of synthesized sample. Nanoparticles and their morphological state were determined by FE-SEM. Based on morphological characteristics analyzing with proposed method the samples were separated into two groups of "appropriate" and "inappropriate". Chemometrics methods such as principal component analysis, cluster analysis (CA) and linear discriminate analysis (LDA) were used to classify chitosan nanoparticles in terms of morphology. The percent of correctly classified samples using LDA were 100 %and 90% for training and test sets, respectively.

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          Most cited references30

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          Insight on the formation of chitosan nanoparticles through ionotropic gelation with tripolyphosphate.

          This work reports details pertaining to the formation of chitosan nanoparticles that we prepare by the ionic gelation method. The molecular interactions of the ionic cross-linking of chitosan with tripolyphosphate have been investigated and elucidated by means of all-electron density functional theory. Solvent effects have been taken into account using implicit models. We have identified primary-interaction ionic cross-linking configurations that we define as H-link, T-link, and M-link, and we have quantified the corresponding interaction energies. H-links, which display high interaction energies and are also spatially broadly accessible, are the most probable cross-linking configurations. At close range, proton transfer has been identified, with maximum interaction energies ranging from 12.3 up to 68.3 kcal/mol depending on the protonation of the tripolyphosphate polyanion and the relative coordination of chitosan with tripolyphosphate. On the basis of our results for the linking types (interaction energies and torsion bias), we propose a simple mechanism for their impact on the chitosan/TPP nanoparticle formation process. We introduce the β ratio, which is derived from the commonly used α ratio but is more fundamental since it additionally takes into account structural details of the oligomers.
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            Biodistribution of fluoresceinated dextran using novel nanoparticles evading reticuloendothelial system.

            The rapid clearance of circulating nanoparticles from the blood stream coupled with their high uptake by liver and spleen has thus far been overcome by reducing the particle size, and by making the particle surface hydrophilic with poloxamers and poloxamines. We have prepared hydrogel nanoparticles of polyvinylpyrrolidone of a size less than 100 nm diameter with precise size distribution. Since the inner cores of these particles are also hydrophilic, these particles are capable of encapsulating water-soluble compounds. Biodistribution of these particles shows practically negligible (<1%) uptake by the macrophages in liver and spleen, and approximately 5-10% of these particles remain in circulation even 8 h after i.v. injection. Increasing the surface hydrophobicity as well as particle size can increase the RES uptake of these particles. Because of longer residence in blood, the hydrogel nanoparticles have potential therapeutic applications particularly in cancer: the water-soluble cytotoxic agents encapsulated in these particles can be targeted to tumors while minimizing the likelihood of toxicity to reticuloendothelial system (RES).
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              Docetaxel Loaded PEG-PLGA Nanoparticles: Optimized Drug Loading, In-vitro Cytotoxicity and In-vivo Antitumor Effect

              In this study a 3-factor, 3-level Box-Behnken design was used to prepare optimized docetaxel (DTX) loaded pegylated poly lactide-co-glycolide (PEG-PLGA) Nanoparticles (NPs) with polymer concentration (X1), drug concentration (X2) and ratio of the organic to aqueous solvent (X3) as the independent variables and particle size (Y1), poly dispersity index (PDI) (Y2) and drug loading (Y3) as the responses. The cytotoxicity of optimized DTX loaded PEG-PLGA NPs was studied in SKOV3 tumor cell lines by standard MTT assay. The in-vivo antitumor efficacy of DTX loaded PLGA-PEG NPs was assessed in tumor bearing female BALB/c mice. The optimum level of Y1, Y2 and Y3 predicted by the model were 188 nm, 0.16 and 9% respectively with perfect agreement with the experimental data. The in-vitro release profile of optimum formulation showed a burst release of approximately 20% (w/w) followed by a sustained release profile of the loaded drug over 288 h. The DTX loaded optimized nanoparticles showed a greater cytotoxicity against SKOV3 cancer cells than free DTX. Enhanced tumor-suppression effects were achieved with DTX-loaded PEG-PLGA NPs. These results demonstrated that optimized NPs could be a potentially useful delivery system for DTX as an anticancer agent.
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                Author and article information

                Journal
                Iran J Pharm Res
                Iran J Pharm Res
                IJPR
                Iranian Journal of Pharmaceutical Research : IJPR
                Shaheed Beheshti University of Medical Sciences (Tehran, Iran )
                1735-0328
                1726-6890
                Summer 2015
                : 14
                : 3
                : 665-675
                Affiliations
                [1] Department of Chemistry, Faculty of Science, International University of Imam Khomeini, Qazvin, Iran.
                Author notes
                [* ]Corresponding author: Email: k.elmizadeh@yahoo.com
                Article
                ijpr-14-665
                4518095
                26330855
                fe7828c0-03cb-4f06-9ceb-ff8e7160e302
                © 2015 by School of Pharmacy, Shaheed Beheshti University of Medical Sciences and Health Services

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : January 2014
                : November 2014
                Categories
                Original Article

                chitosan nanoparticles,drift spectroscopy,chemometrics,particle size

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