Browsing by Author "Morris, VB"

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    Folic acid-conjugated depolymerized quaternized chitosan as potential targeted gene delivery vector
    (POLYMER INTERNATIONAL, 2011) Morris, VB; Pillai, CKS; Sharma, CP
    Ligand-conjugated delivery vectors that target over-expressed cell surface receptors have a potential impact on gene therapy. In the study reported, high-molecular-weight chitosan was depolymerized to medium and low molecular weight and trimethylated to render the polymer soluble over a wider pH range. Folate conjugation was introduced to the quartemized derivative to improve gene transfection efficiency. Complexes of the folic acid-conjugated trimethylated depolymerized chitosan (FTMC) with plasmid DNA (pDNA) formed core-shell nanostructured particles. Gel electrophoretic band retardation showed efficient condensation of DNA. These derivatives and their complexes with pDNA were tested for toxicity and haemocompatibility and were found to be significantly less toxic and haemocompatible than polyethyleneimine. Transfection efficiency and nuclear uptake properties were tested in the human KB oral epidermoid cell line, which over-expresses the folate receptor in the presence of 10% serum. Among the four FTMC derivatives investigated, folic acid-conjugated chitosan having low molecular weight and medium folate conjugation was found to be a potential vector for gene delivery applications with good transfection and nuclear uptake properties, as proved by YOYO labelling of pDNA. (C) 2011 Society of Chemical Industry
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    Studies on the Condensation of Depolymerized Chitosans With DNA for Preparing Chitosan-DNA Nanoparticles for Gene Delivery Applications
    (JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS, 2009) Morris, VB; Neethu, S; Abraham, TE; Pillai, CKS; Sharma, CP
    High molecular weight chitosan (CS) was depolymerized by oxidative degradation with NaNO(2) at room temperature to get 11 samples of CS derivatives of varying molecular weights with a view to assessing their effective molecular weight range for gene delivery applications. Viscosity studies indicated that the molecular weight of the depolymerized CS was proportional to the CS/NaNO(2) ratio. The condensation behavior of DNA/CS complexes at various charge ratios was studied using UV spectroscopy, FTIR, CD, SEM, and AFM. The results indicated that CSs having very low molecular weights and high charge density exhibited strong binding affinity to DNA compared to high molecular weight CSs. However, the very low molecular weight (1.9-7.7 kDa) CSs were found to form aggregates easily even at very low charge ratios. On the other hand, CSs having medium molecular weight (49-51 kDa) and high degree of deacetylation (DD) gave stable uniform-sized nanoparticles. Biological studies carried out with the spherical nano-sized polyplexes formed between CS of 50 kDa (DD of 94%) and pEGFP plasmid DNA at NIP ratio of 5.0 showed excellent gene transfection efficiency at pH 6.5 in HeLa cells without cytotoxicity indicating their potential as gene delivery carriers. (C) 2008 Wiley Periodicals. Inc. J Biomed Mater Res Part 13: Appl Biomater 89B: 282-292,2009