Surface modification of lipid nanocapsules with polysaccharides: From physicochemical characteristics to in vivo aspects

Abstract

Attaching polysaccharides to the surface of nanoparticles offers the possibility of modifying the physicochemical and biological properties of the core particles. The surface of lipid nanocapsules (LNCs) was modified by post-insertion of amphiphilic lipochitosan (LC) or lipodextran (LD). Modelling of these LNCs by the drop tensiometer technique revealed that the positively charged LC made the LNC surface more rigid, whereas the neutral, higher M(W) LD had no effect on the surface elasticity. Both LNC-LC and LNC-LD activated the complement system more than the blank LNC, thus suggesting increased capture by the mononuclear phagocyte system. In vitro, the positively charged LNC-LC were more efficiently bound by the model HEK293(β3) cells compared to LNC and LNC-LD. Finally, it was observed that neither LC nor LD changed the in vivo biodistribution properties of LNCs in mice. These polysaccharide-coated LNCs, especially LNC-LC, are promising templates for targeting ligands (e.g. peptides, proteins) or therapeutic molecules (e.g. siRNA).

Functionalizing Nanoemulsions with Carboxylates: Impact on the Biodistribution and Pharmacokinetics in Mice

“…The values of p are 3.3% and 2.5% for samples in PBS and MilliQ water, respectively. The colorimetric method appears efficient for evaluating the number of charged species at the interface of nanoparticles, and the number of functions disclosed is compatible with the aimed applications, and as well, largely exceeding the published examples of nanoemulsion functionalization, e.g., below 40 per droplet . However, it is to be noted that several studies regarding the surface functional group quantification, notably carboxylic acid, have some limitation, and only a small but constant fraction of the surface functional groups is accessible to potential covalent surface derivatization, independently of the total number of surface functional groups .…”

“…On the other hand, advantages of nanoemulsions over these nanoparticles are their loading capability, possibilities of co‐encapsulation of different molecules with very high concentrations . Some reports show the modification of droplet surface by post‐insertion of functionalizable lipids like DSPE‐PEG 2000‐maleimide (1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐ N ‐[maleimide (polyethylene glycol)‐2000]), which consists of incubating a micellar solution of this DSPE‐PEG 2000‐maleimide with the suspension of lipid nanodroplets. As a result, a small fraction of the lipid will be inserted at the oil/water interface that allows to display around 40 functionalized sites per droplet .…”

“…Some reports show the modification of droplet surface by post‐insertion of functionalizable lipids like DSPE‐PEG 2000‐maleimide (1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐ N ‐[maleimide (polyethylene glycol)‐2000]), which consists of incubating a micellar solution of this DSPE‐PEG 2000‐maleimide with the suspension of lipid nanodroplets. As a result, a small fraction of the lipid will be inserted at the oil/water interface that allows to display around 40 functionalized sites per droplet . which is rather low compared to the grafting efficiency obtained with polymer or inorganic nanoparticles .…”

Safe lipid nanocapsule-based gel technology to target lymph nodes and combat mediastinal metastases from an orthotopic non-small-cell lung cancer model in SCID-CB17 mice

“…The fluorescent dye DiD was chosen to be encapsulated in the LNCs because (i) it is a near-infrared fluorophore limiting the auto-fluorescence wavelength emitted by animals, [25][26][27] (ii) it is weakly fluorescent in aqueous media, but highly fluorescent in a lipophilic vehicle, 28 and (iii) there is no dye release (strong fluorescence labeling stability of the nanocarrier). 29 The semi-quantitative fluorescence of the organs extracted after 1, 4, 8, 48, 96, and 336 h is reported in Figure 1, C-F and Figure S1 in supplementary information.…”

Passive and specific targeting of lymph nodes: the influence of the administration route

“…For this purpose, DiD was encapsulated in LNCs because the fluorescence and physico-chemical properties of DiD supported the choice of this fluorescence labeling. It is highly fluorescent in lipophilic nanocarriers and weakly fluorescent in aqueous media (19); the auto-fluorescence wavelength emitted by animals is limited because it is a near-infrared fluorophore (20,21), and there is a strong fluorescence labeling stability of the nanocarrier (no DiD release even in favorable media) (16).…”