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: 5.98). 10/2007; 3(3):173-83. DOI: 10.1016/j.nano.2007.03.006
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Many methods have been developed in order to use of calcium phosphate (CaP) in delivering nucleotides into the living cells. Surface functionalization of CaP nanoparticles (CaP NPs) with N-(2-aminoethyl)-3-aminopropyltrimethoxysilane was shown recently to achieve dispersed NPs with a positive surface charge, capable of transfection (Chemistry of Materials 2013, 25 (18):3667). In this study, different crystal structures of amino-modified CaP NPs (brushite and hydroxyapatite) were investigated for their interaction in cell culture systems in more detail. Qualitative (confocal laser scanning microscopy) and quantitative (flow cytometry) transfection experiments with two cell lines showed the higher transfection efficacy of brushite versus hydroxyapatite. The transfection also revealed a cell type dependency. HEK293 cells were easier to transfect compared to A549 cells. This result was supported by the cytotoxicity results. A549 cells showed a higher degree of tolerance towards the CaP NPs. Further, the impact of the surface modification on the interaction with macrophages and complement as two important components of the innate immune system were considered. The amine surface functionalization had an effect of decreasing the release of proinflammatory cytokines. The complement interaction investigated by a C3a complement activation assay did show no significant differences between CaP NPs without or with amine modification and overall weak interaction. Finally, the degradation of CaP NPs in biological media was studied with respect to the two crystal structures and at acidic and neutral pH. Both amino modified CaP NPs disintegrate within days at neutral pH, with a notable faster disintegration of brushite NPs at acidic pH. In summary, the fair transfection capability of this amino functionalized CaP NPs together with the excellent biocompatibility, biodegradability and low immunogenicity make them interesting candidates for further evaluation.
    ACS Applied Materials & Interfaces 02/2015; DOI:10.1021/am507193a · 5.90 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A series of cyclodextrin-based star polymers were synthesized using β-cyclodextrin (CD) as hydrophilic core, methyl methacrylate (MMA) and tert-butyl acrylate (tBA) as hydrophobic arms. Star polymers, either homopolymers or random/block copolymers, showed narrow molecular weight distributions. Grafting hydrophobic arms created CD-based nanoparticles (CD-NPs) in the size range (130-200nm) with narrow PdI <0.15 and slightly negative ζ-potential. Particle surface could be modified with chitosan to impart a positive surface charge. Colloidal stability of CD-NPs was a function of pH as revealed by the pH-titration curves. CD-NPs were used as carrier for the chemotherapeutic drug idarubicin (encapsulation efficiency, EE ∼40%) ensuring prolonged release profile (∼80% after 48h). For cell-based studies, coumarin-6 was encapsulated as a fluorescent marker (EE ∼75%). Uptake studies carried out on A549 and Caco-2 cell lines proved the uptake of coumarin-loaded NPs as a function of time and preferential localization in the cytoplasm. Uptake kinetics revealed no saturation or plateau over 6h. Chitosan-modified NPs showed significantly improved, concentration-dependent cellular uptake. Meanwhile, CD-NPs were non-cytotoxic on both cell lines over the concentration range (0.25-3mg/ml) as studied by MTT and LDH assays. In conclusion, CD star polymers can be considered a versatile platform for a new class of biocompatible nanochemotherapy. Copyright © 2015 Elsevier B.V. All rights reserved.
    Colloids and surfaces B: Biointerfaces 03/2015; 129. DOI:10.1016/j.colsurfb.2015.03.014 · 4.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Blend microspheres of chitosan and polyurethane (PU) have been prepared by water-in-oil emulsion cross-linking method and used to encapsulate two water-soluble and having widely different plasma half-life cardiovascular drugs, viz., isoxsuprine hydrochloride and calcium dobesilate. The blend miscibility of the polymers was confirmed by differential scanning calorimetry at >60 wt% of PU. The microspheres were characterized by scanning electron microscopy to understand the morphology of the drug-loaded microspheres. Chemical interactions between drug molecules and the carrier polymers have been investigated by Fourier transform spectroscopy. XRD measurements on placebo matrices, drug-loaded formulations and nascent drugs indicated their uniform dispersion in the polymer matrix. In vitro release experiments performed in both acidic pH of 1.2 and alkaline pH of 7.4 increased the release time of both the drugs in the media employed. Kinetics of drug release was analyzed by empirical equation, suggesting the deviation from Fickian transport to non-Fickian trend.
    Polymer Bulletin 02/2014; 72(2):265-280. DOI:10.1007/s00289-014-1271-6 · 1.49 Impact Factor