Trimethyl chitosan and its applications in drug delivery. J Mater Sci Mater Med

Government College of Pharmacy, Vedant Hotel Road, Usmanpura, Aurangabad, India.
Journal of Materials Science Materials in Medicine (Impact Factor: 2.59). 05/2009; 20(5):1057-79. DOI: 10.1007/s10856-008-3659-z
Source: PubMed

ABSTRACT Chitosan, a polymer obtained by deacetylation of chitin is widely studied for its pharmaceutical and nonpharmaceutical applications. Recommendations about uses of this polymer although could not be always realized due to limited solubility. Chitosan, for example, has been extensively evaluated for its mucoadhesive and absorption enhancement properties. The positive charge on the chitosan molecule gained by acidic environment in which it is soluble seems to be important for absorption enhancement. However chitosan is not soluble in medium except below pH 5.6. This limits its use as permeation enhancer in body compartments where pH is high. In this regard there is a need for chitosan derivatives with increased solubility, especially at neutral and basic pH values. Trimethylation of chitosan is an effort in this direction. Despite the abundance of the research related to trimethyl chitosan (TMC), the overview of the topic is not available. Hence an attempt is made in this review to cover the recent findings pertaining to synthesis, characterization and applications of TMC especially in pharmaceutical field. TMC has been synthesized by different ways and characterized by FTIR, NMR, DSC etc. This quaternized derivative of chitosan possesses a positive charge and is soluble over a wide range of pH. TMC, being a derivative of cationic polymer enriched with positive charge shows better mucoadhesive, permeation enhancement, drug delivery and DNA delivery properties. TMC can be further derivitized or grafted for modulating properties as solubility, cytotoxicity or cell recognition ability. Apart from these applications, TMC itself and its derivatives exhibit antimicrobial properties also. Quaternization of chitosan not only with methyl group but higher group as ethyl or along with spacer or quaternization of modified chitosan can be of interest too.

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Available from: Nazma Inamdar, Sep 28, 2015
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    • "To address this weakness, a partially quaternized chitosan derivative, known as N-trimethyl chitosan chloride (TMC), was synthesized and evaluated at different degrees of substitution as a safe and efficient permeation enhancer in vitro [18] [19] [20] [21]. TMC shows mucoadhesive characteristic and enhanced absorption effects even at neutral pH due to its permanent cationic charge and good water solubility over a wide pH range [17] [18]. Therefore, niosomal nanocarriers coated with TMC can be a viable candidate for oral delivery of proteins and peptide drugs as they are able to overcome some of the inherent limitations related to these molecules [22] [23] [24] [25] [26]. "
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    ABSTRACT: This study reports the development of a highly stable niosomal nanostructure based on Span 60/cholesterol (CH)/N-trimethyl chitosan (TMC) system and its potential application for oral delivery of insulin. Insulin loaded niosomes were prepared by reversed-phase evaporation and TMC coating was performed by incubation of niosomal suspensions with TMC solution. The efficiency of nanoparticulate delivery system in enhancement of insulin permeation was evaluated by Caco-2 cell monolayer as intestinal membrane models. The prepared niosomes were characterized for entrapment efficiency (EE), particle size, zeta potential and stability. The particles were between 100 and 180 nm in diameter, and theywere stable for over 60 days at 4 °C. Insulin permeability through Caco-2 cell monolayer was enhanced 4-fold by niosomal nanoparticles, compared with insulin alone. Further work is demanded to optimize this formulation with the object of maximizing its potential to facilitate oral delivery of insulin.
    Materials Science and Engineering C 10/2014; 46(1):333-340. DOI:10.1016/j.msec.2014.10.070 · 3.09 Impact Factor
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    • "M CH3COOH eluent at a flow rate of 1 mL.min−1 (MW 43.3 kDa). TMC degree of quaternization (DQ) was determined by 1H-Nuclear Magnetic Resonance (Bruker Avance II); samples were dissolved in D2O (2 mg.mL−1) at 60°C overnight; the DQ was calculated according to Mourya [29] (30.1%). Degree of acetylation was calculated by FTIR (11.1%). "
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    ABSTRACT: Development of effective non-viral vectors is of crucial importance in the implementation of RNA interference in clinical routine. The localized delivery of siRNAs to the gastrointestinal mucosa is highly desired but faces specific problems such as the stability in gastric acidity conditions and the presence of the mucus barrier. CDX2 is a transcription factor critical for intestinal differentiation being involved in the initiation and maintenance of gastrointestinal diseases. Specifically, it is the trigger of gastric intestinal metaplasia which is a precursor lesion of gastric cancer. Its expression is also altered in colorectal cancer, where it may constitute a lineage-survival oncogene. Our main objective was to develop a nanoparticle-delivery system of siRNA targeting CDX2 using modified chitosan as a vector. CDX2 expression was assessed in gastric carcinoma cell lines and nanoparticles behaviour in gastrointestinal mucus was tested in mouse explants. We show that imidazole-modified chitosan and trimethylchitosan/siRNA nanoparticles are able to downregulate CDX2 expression and overpass the gastric mucus layer but not colonic mucus. This system might constitute a potential therapeutic approach to treat CDX2-dependent gastric lesions.
    PLoS ONE 06/2014; 9(6):e99449. DOI:10.1371/journal.pone.0099449 · 3.23 Impact Factor
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    • "Many novel chitosan derivatives have been obtained by chemical modification (Ravi Kumar and others 2004; Holappa and others 2006a). Quaternary ammonium chitosans, a kind of chitosan derivatives with permanent cationic charges on the polysaccharide backbone, have attracted much attention to be used as bacteriostatic agents (Rúnarsson and others 2007), textile finishing agents (Lim and Hudson 2004), and drug delivery carriers (Mourya and Inamdar 2009). That is because chitosan modified with quaternary ammonium salts can become water-soluble and exhibit better antimicrobial activity than unmodified chitosan (Li and others 2011). "
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    ABSTRACT: Total of 3 water-soluble quaternary-based chitin/chitosan derivatives, which have an identical molecular weight and anion, were synthesized and characterized. Their antibacterial activities against Salmonella cholerae-suis and Bacillus subtilis were evaluated in vitro. The polysaccharides exhibited the antibacterial efficiency. Their minimum inhibitory concentration (MIC) values vary from 0.02 to 20.48 mg/mL, and their minimum bactericidal concentration (MBC) values vary from 0.08 to 40.96 mg/mL against S. cholerae-suis and B. subtilis, respectively. Futhermore, the extent of Bacillus subtilis cells damage was examined via transmission electron microscopy (TEM) to show how N,N,N-trimethylchitosan (TMC) gradually destroyed and killed B. subtilis cells when they were treated with TMC. One of those quaternary polymers, O-([2-hydroxy-3-trimethylammonium])propyl chitin (OHT-chitin), which can be directly and easily synthesized from chitin in bulk quantities, also was demonstrated its antibacterial activity. These water soluble quaternary-based chitin/chitosan derivatives that have antibacterial effect should be potentially used as antimicrobial agents in many fields. Practical Application: The main practical application behind the investigation and evaluation antibacterial activity of 3 water-soluble quaternary-based chitin/chitosan derivatives could be potentially used as antimicrobial agents in many fields. These polysaccharides represent a renewable source of natural biodegradable polymers and meet with the emergence of more and more food safe problems.
    Journal of Food Science 01/2013; 78(1):M90-7. DOI:10.1111/j.1750-3841.2012.02999.x · 1.70 Impact Factor
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