Article

Insight on the Formation of Chitosan Nanoparticles through Ionotropic Gelation with Tripolyphosphate.

Laboratory of Molecular Engineering, Department of Physics, University of Patras , Patras GR-26500, Greece.
Molecular Pharmaceutics (Impact Factor: 4.57). 07/2012; 9(10):2856-62. DOI: 10.1021/mp300162j
Source: PubMed

ABSTRACT 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.

2 Bookmarks
 · 
345 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The application of RNA interference (RNAi) for inflammatory bowel disease (IBD) therapy has been limited by the lack of non-cytotoxic, efficient and targetable small interfering RNA (siRNA) carriers. TNF-α is the major pro-inflammatory cytokine mainly secreted by macrophages during IBD. Here, a mannosylated bioreducible cationic polymer (PPM) was synthesized and further spontaneously assembled nanoparticles (NPs) assisted by sodium triphosphate (TPP). The TPP-PPM/siRNA NPs exhibited high uniformity (polydispersity index = 0.004), a small particle size (211-275 nm), excellent bioreducibility, and enhanced cellular uptake. Additionally, the generated NPs had negative cytotoxicity compared to control NPs fabricated by branched polyethylenimine (bPEI, 25 kDa) or Oligofectamine (OF) and siRNA. In vitro gene silencing experiments revealed that TPP-PPM/TNF-α siRNA NPs with a weight ratio of 40:1 showed the most efficient inhibition of the expression and secretion of TNF-α (approximately 69.9%, which was comparable to the 71.4% obtained using OF/siRNA NPs), and its RNAi efficiency was highly inhibited in the presence of mannose (20 mm). Finally, TPP-PPM/siRNA NPs showed potential therapeutic effects on colitis tissues, remarkably reducing TNF-α level. Collectively, these results suggest that non-toxic TPP-PPM/siRNA NPs can be exploited as efficient, macrophage-targeted carriers for IBD therapy.
    Biomaterials 06/2013; · 7.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A new nanoparticulate system for foscarnet delivery was prepared and evaluated. Nanoparticles were obtained by ionotropic gelation of chitosan induced by foscarnet itself, acting as an ionotropic agent in a manner similar to tripolyphosphate anion. A Doehlert design allowed finding the suitable experimental conditions. Nanoparticles were between 200 and 300nm in diameter (around 450nm after redispersion). Nanoparticle size increased after 5h, but no size increase was observed after 48h when nanoparticles were crosslinked with glutaraldehyde. Zeta potential values of noncrosslinked and crosslinked nanoparticles were between 20 and 25mV, while drug loading of noncrosslinked nanoparticles was about 40% w/w (55% w/w for crosslinked nanoparticles). Nanoparticle yield was around 25% w/w. Crosslinked nanoparticles showed a controlled drug release. Foscarnet released from nanoparticles maintained the antiviral activity of the free drug when tested in vitro against lung fibroblasts (HELF) cells infected with HCMV strain AD-169. Moreover, nanoparticles showed no toxicity on non-infected HELF cells. These nanoparticles may represent a delivery system that could improve the therapeutic effect of foscarnet.
    Colloids and surfaces B: Biointerfaces 03/2014; 118C:117-125. · 3.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the effect of polyelectrolytes on the formation and physicochemical properties of chitosan nanoparticles (CS-NPs) used for the delivery of an anticancer drug, doxorubicin (DOX). Three DOX-loaded CS-NPs were formulated with tripolyphosphate (CS-TP/DOX NPs), dextran sulfate (CS-DS/DOX NPs), and hyaluronic acid (CS-HA/DOX NPs) by using ionotropic gelation or complex coacervation. CS-TP/DOX NPs were the smallest, with an average size of ~100 nm and a narrow size distribution, while CS-DS/DOX and CS-HA/DOX NPs were ~200 nm in size. Transmission electron microscopy clearly showed a spherical shape for all the NPs. The strong binding affinity of DOX for the multiple sulfate groups in DS resulted in a sustained release profile from CS-DS/DOX NPs at pH 7.4, while CS-HA/DOX NPs exhibited faster DOX release. This trend was also present under acidic conditions, where release of DOX was significantly augmented because of polymer protonation. Compared to CS-TP/DOX or CS-DS/DOX NPs, CS-HA/DOX NPs showed superior cellular uptake and cytotoxicity in MCF-7 and A-549 cells, because of their ability to undergo CD44-mediated endocytosis. Pharmacokinetic studies clearly showed that all CS-NPs tested significantly improved DOX plasma circulation time and decreased its elimination rate constant. Consistent with the in vitro release data, CS-DS/DOX NPs exhibited a relatively better DOX plasma profile and enhanced blood circulation, compared to CS-HA/DOX or CS-TP/DOX NPs. Overall, these results demonstrated how NP design can influence their function. Taken together, CS-based polyelectrolyte complexes could provide a versatile delivery system with enormous potential in the pharmaceutical and biomedical sectors.
    Pharmaceutical Research 12/2013; · 4.74 Impact Factor

Full-text

View
62 Downloads
Available from
Jun 6, 2014