Chitosan–DNA complexes: Effect of molecular parameters on the efficiency of delivery

Bordi, F.; Chronopoulou, Laura; Palocci, Cleofe; Bomboi, Francesca; Martino, Antonio Di; Cifani, Noemi; Pompili, Barbara; Ascenzioni, Fiorentina; Sennato, Simona

doi:10.1016/j.colsurfa.2013.12.022

Cited by 32 publications

(23 citation statements)

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“…The possibility to get a fine control of the stability of the complexes by tuning the competition between attractive and repulsive electrostatic interactions justifies the actual enduring attention on polyion-colloid complexation, being key to the technological development of nano-structured materials or nano-devices to be used for example in drug delivery or gene-therapy [9,10].…”

Section: Introductionmentioning

confidence: 99%

Salt-induced reentrant stability of polyion-decorated particles with tunable surface charge density

Sennato

Carlini

Truzzolillo

et al. 2016

Colloids and Surfaces B: Biointerfaces

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The electrostatic complexation between DOTAP/DOPC unilamellar liposomes and an oppositely charged polyelectrolyte (NaPA) has been investigated in a wide range of the liposome surface charge density. We systematically characterized the reentrant condensation and the charge inversion of polyelectrolyte-decorated liposomes by means of dynamic light scattering and electrophoresis. We explored the stability of this model polyelectrolyte/colloid system at different values of the surface charge of the bare liposomes and by changing two independent control parameters of the suspensions: the polyelectrolyte/colloid charge ratio and the ionic strength of the aqueous suspending medium. The progressive addition of neutral DOPC lipid within the liposome membrane gave rise to an interesting phenomenon which has not been observed previously: the stability diagram of the suspensions showed a novel reentrance due to the crossing of the desorption threshold of the polyelectrolyte. Indeed, at fixed charge density of the bare DOTAP/DOPC liposomes and for a wide range of polyion concentrations, we showed that the simple electrolyte addition first (low salt regime) destabilizes the suspensions because of the enhanced screening of the residual repulsion between the complexes, and then (high salt regime) determines the onset of a new stable phase, originated by the absence of polyelectrolyte adsorption on the particle surfaces. We show that the observed phenomenology can be rationalized within the modified Velegol-Thwar model for heterogeneously charged particles and that the polyelectrolyte desorption fits well the predictions of the adsorption theory of Winkler and Cherstvy [1]. Our findings unambiguously support the picture of the reentrant condensation as driven by the correlated adsorption of the polyelectrolyte chains on the particle surface, providing interesting insights into possible mechanisms for tailoring complex colloids via salt-induced effects.

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Section: Introductionmentioning

confidence: 99%

Salt-induced reentrant stability of polyion-decorated particles with tunable surface charge density

Sennato

Carlini

Truzzolillo

et al. 2016

Colloids and Surfaces B: Biointerfaces

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“…These polyplexes were *150 nm in size, and had largely positive f-potential, irrespective of the chitosan molecular weight (Table 2). Overall, as we recently reported (Bordi et al 2014), the chitosan/ pDNA assembly and complex morphology were governed by the N/P ratio, and were instead independent of the chitosan molecular weight and degree of deacetylation (Buschmann et al 2013).…”

Section: Resultsmentioning

confidence: 81%

“…The images in Fig. 1 suggested a closely packed structure that might have originated through a compaction process of intermediate complexes (Bordi et al 2014). These polyplexes were *150 nm in size, and had largely positive f-potential, irrespective of the chitosan molecular weight (Table 2).…”

Section: Resultsmentioning

confidence: 96%

“…In all cases, the polydispersity index (i.e., M w /M n ratio), was close to 1, which indicates low dispersion. Next, we selected the 3.3 and 15 kDa chitosan oligomers, in addition to commercial chitosans of 50 kDa and 150 KDa, to assemble the chitosan/pDNA complexes (Bordi et al 2014). …”

Section: Resultsmentioning

confidence: 99%

“…The pH was adjusted to 7, and the suspension was centrifuged at 2,0009g for 30 min, and the pellet was recovered and freeze-dried. Chitosan was depolymerized according to Bordi et al (2014), with the molecular weights of the oligomers obtained determined by gel permeation chromatography. Here, 1 % (w/v) chitosan samples in 0.1 M acetate buffer (pH 4.0) were run at a flow rate of 0.8 ml/min.…”

Section: Chitosan Depolymerization and Characterizationmentioning

confidence: 99%

See 2 more Smart Citations

Improved stability and efficacy of chitosan/pDNA complexes for gene delivery

et al. 2014

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Among polymeric polycations, chitosan has emerged as a powerful carrier for gene delivery. Only a few studies have focused on the stability of the chitosan/DNA complex under storage, although this is imperative for nanomedicinal applications. Here, we synthesized polyelectrolyte complexes at a charge ratio of 10 using 50 kDa chitosan and plasmid (p)DNA that encodes a GFP reporter. These preparations were stable up to 3 months at 4 °C and showed reproducible transfection efficiencies in vitro in HEK293 cells. In addition, we developed a methodology that increases the in vitro transfection efficiency of chitosan/pDNA complexes by 150% with respect to standard procedures. Notably, intracellular pDNA release and transfected cells peaked 5 days following transection of mitotically active cells. These new developments in formulation technology enhance the potential for polymeric nanoparticle-mediated gene therapy.

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