Chitosan-coated PLGA nanoparticles for DNA/RNA delivery: Effect of the formulation parameters on complexation and transfection of antisense oligonucleotides

Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany.
Nanomedicine: nanotechnology, biology, and medicine (Impact Factor: 6.16). 10/2007; 3(3):173-83. DOI: 10.1016/j.nano.2007.03.006
Source: PubMed


Cationically modified poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles have recently been introduced as novel carriers for DNA/RNA delivery. The colloidal characteristics of the nanoparticles--particle size and surface charge--are considered the most significant determinants in the cellular uptake and trafficking of the nanoparticles. Therefore, our aim was to introduce chitosan-coated PLGA nanoparticles, whose size and charge are tunable to adapt for a specific task. The results showed that biodegradable nanoparticles as small as 130 nm and adjustable surface charge can be tailored controlling the process parameters. As a proof of concept, the overall potential of these particulate carriers to bind the antisense oligonucleotides, 2'-O-methyl-RNA, and improve their cellular uptake was demonstrated. The study proved the efficacy of chitosan-coated PLGA nanoparticles as a flexible and efficient delivery system for antisense oligonucleotides to lung cancer cells.

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Available from: Claus-Michael Lehr, Oct 17, 2015
    • "Among those, NPs show high potential to control the delivery of various APIs (Conti et al., 1991; Sanders et al., 1984). Many polymeric matrix materials have been intensively investigated in this context, including poly(D,L-lactic-co-glycolic acid) (P, PLGA) (Dillen et al., 2004; Fonseca et al., 2002; Govender et al., 1999; Lemoine and Préat, 1998; Nafee et al., 2007), chitosan (Janes et al., 2001; Prabha et al., 2002; Rhim et al., 2006), poly-ɛ-caprolactone (Gan et al., 1999; Leroueil- Le Verger et al., 1998), starch (Kreuter, 1991; Le Corre et al., 2010), alginate (Johnson et al., 1997; Sarmento et al., 2006) and gelatin (Balthasar et al., 2005; Khan and Schneider, 2013; Truong-Le et al., 1999). One of the most common biodegradable and biocompatible polymers (Langer and Peppas, 1981) used to prepare NPs for the encapsulation of proteins, via the waterin-oil-in-water (w/o/w) double emulsion method, is PLGA. "
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    ABSTRACT: The effect of modifying the well-established pharmaceutical polymer PLGA by different PEG-containing block-copolymers on the preparation of ovalbumin (OVA) loaded PLGA nanoparticles (NPs) was studied. The used polymers contained poly(D,L-lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG) and poly(allyl glycidyl ether) (PAGE) as building blocks. The double emulsion technique yielded spherical NPs in the size range from 170 to 220 nm (PDI < 0.15) for all the differently modified polymers, allowing to directly compare protein loading of and release. PEGylation is usually believed to increase the hydrophilic character of produced particles, favoring encapsulation of hydrophilic substances. However, in this study simple PEGylation of PLGA had only a slight effect on protein release. In contrast, incorporating a PAGE block between the PEG and PLGA units, also eventually enabling active targeting introducing a reactive group, led to a significantly higher loading (+ 25%) and release rate (+ 100%), compared to PLGA and PEG-b-PLGA NPs.
    No preview · Article · Jan 2016 · International Journal of Pharmaceutics
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    • "Chitosan-coated PLGA ENP (172.3 AE 4.5 nm) were shown to be a flexible and efficient system for delivery of antisense oligonucleotides to lung cancer cells (Nafee et al., 2007). Overall, organic and biodegradable polysaccharide-based ENP can effectively inhibit disease in models of allergic asthma and other inflammatory lung diseases. "
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    ABSTRACT: Abstract Engineered nanoparticles (ENP), which could be composed of inorganic metals, metal oxides, metalloids, organic biodegradable and inorganic biocompatible polymers, are being used as carriers for vaccine and drug delivery. There is also increasing interest in their application as delivery agents for the treatment of a variety of lung diseases. Although many studies have shown ENP can be effectively and safely used to enhance the delivery of drugs and vaccines in the periphery, there is concern that some ENP could promote inflammation, with unknown consequences for lung immune homeostasis. In this study, we review research on the effects of ENP on lung immunity, focusing on recent studies using diverse animal models of human lung disease. We summarize how the inflammatory and immune response to ENP is influenced by the diverse biophysical and chemical characteristics of the particles including composition, size and mode of delivery. We further discuss newly described unexpected beneficial properties of ENP administered into the lung, where biocompatible polystyrene or silver nanoparticles can by themselves decrease susceptibility to allergic airways inflammation. Increasing our understanding of the differential effects of diverse types of nanoparticles on pulmonary immune homeostasis, particularly previously underappreciated beneficial outcomes, supports rational ENP translation into novel therapeutics for prevention and/or treatment of inflammatory lung disorders.
    Full-text · Article · Nov 2013 · Drug Metabolism Reviews
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    • "The preparation of FA-Chitosan-PLGA particles was based on the solvent evaporation method by Nafee [19]. PLGA (80 mg) and FA-PLGA (20 mg) were dissolved as organic phase (O) in 10 mL ethyl acetate. "
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    ABSTRACT: The systemic therapy of inflammatory bowel diseases (IBD) by oral administration of anti-inflammatory and immunosuppressive agents is characterized by an increased probability of adverse drug reactions. A successful treatment with a simultaneous reduction of adverse events may be achieved by the administration of micro- and nanosized targeted drug delivery systems, which accumulate selectively in inflamed mucosal areas without systemic absorption. We described in a first in vivo study in IBD patients a significantly enhanced, but minor accumulation of non-functionalized poly(lactic-co-glycolic acid) (PLGA) microparticles in ulcerous lesions very recently. The aim of this study was therefore the assessment of an increased targeting potential of different non-, chitosan- and polyethylene glycol (PEG)-functionalized PLGA micro- and nanoparticles to inflamed intestinal mucosa compared to healthy mucosa. For the quantification of nano- and microparticles, fluoresceinamine-labeled-PLGA was synthesized by carbodiimide reaction. Fluorescent chitosan-, PEG-, and non-functionalized PLGA micro- and nanoparticles with mean hydrodynamic diameters of 3000 nm and 300 nm were prepared by solvent evaporation technique. The targeting efficiencies in terms of particle translocation and deposition were investigated in Ussing chamber experiments. Healthy and inflamed macrobiopsies were received from routine endoscopic examinations of patients with IBD as well as control patients. 101 Ussing chamber experiments of patients with IBD (Crohńs disease: n = 7 and ulcerative colitis: n = 9) as well as healthy control patients (n=5) were performed. Histomorphological and electrophysiological investigations of inflamed mucosal tissues confirmed a significant alteration of mucosal barrier integrity in IBD patients (TER: healthy: 34.1 Ω x cm(2); inflamed: 21.6 Ω x cm(2); p=0.034). In summary, nanoparticles showed an increased translocation and deposition compared to microparticles in healthy and in inflamed mucosa. Chitosan-functionalized particles adhered onto the tissue surface and thus showed the lowest particle translocation and deposition in healthy and inflamed tissues. PEG-functionalized nanoparticles showed the highest translocation through healthy (2.31%) and inflamed mucosa (5.27%). Moreover, PEG-functionalized microparticles showed a significantly increased translocation through inflamed mucosa (3.33%) compared to healthy mucosa (0.55%; p=0.045). Notably, the particle deposition of PEG-functionalized microparticles was significantly increased in inflamed mucosa (10.8%) compared to healthy mucosa (4.1%; p=0.041). Based on the targeted translocation and deposition to inflamed intestinal mucosa, PEG-functionalized PLGA microparticles were qualified as an innovative drug delivery system. These particles may serve as a selective treatment strategy to inflamed mucosal areas in IBD with the potential to improve therapeutic efficacy and to reduce adverse events.
    Full-text · Article · Sep 2013 · European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
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