Influence of size, surface coating and fine chemical composition on the in vitro reactivity and in vivo biodistribution of lipid nanocapsules versus lipid nanoemulsions in cancer models

Hirsjärvi, Samuli; Dufort, Sandrine; Gravier, Julien; Texier, Isabelle; Qiao, Yan; Bibette, Jérôme; Sancey, Lucie; Josserand, Véronique; Passirani, Catherine; Benoit, Jean‐Pierre; Coll, Jean‐Luc

doi:10.1016/j.nano.2012.08.005

Cited by 69 publications

(51 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This obtained in vivo distribution is in line with the stability in human serum against the formation of high molecular weight aggregates. DLS analysis showed that only PS-LUT-NH 2 particles have a radius of < 100 nm in undiluted serum solution, which makes a longer and more efficient body distribution more likely [33]. Moreover, studies in whole blood showed a high uptake of this particle in monocytes as well as in granulocytes, whereas all other particles are only taken up in significant amounts in monocytes.…”

Section: Discussionmentioning

confidence: 99%

Aggregation Behavior of Polystyrene-Nanoparticles in Human Blood Serum and its Impact on the in vivo Distribution in Mice

Mohr

Sommer²,

Baier

et al. 2014

J Nanomed Nanotechnol

View full text Add to dashboard Cite

The interactions between nanoparticles (NPs) and proteins in complex biological application media such as blood serum are capable of inducing aggregate formation which can lead to subsequent changes in biological activity. Here, we correlate surface charge, aggregation-tendency, and surface serum protein adsorption with cellular uptake and biodistribution in mice.Polystyrene-based NPs (80 -170 nm) with different surface functionalizations were synthesized and incubated with human serum. Interaction of NPs with serum proteins and aggregate formation were analyzed by mass spectrometryanalysis and dynamic light-scattering. Influence of surface functionalization on specific cellular uptake and organdistribution was characterized.Localization and organ targeting of intravenously applied NPs preferentially depended on their aggregationbehavior in the presence of serum. Whereas strongly aggregating particles mainly located to liver, non-aggregating particles distributed to all organs. Determination of aggregate formation of NPs in the presence of serum and further analysis of the protein corona allows for pre-selection of NPs for in vivo application. studies were done by dynamic light scattering applying a previously developed pre-in vivo screening method [10]. This enabled us to analyze the effect of surface functionalization on aggregation and protein binding in the presence of human serum under physiologically relevant conditions. To allow analyzing the cellular uptake of NPs in cells of the peripheral blood as well as in professional antigen-presenting cells, the NPs were fluorescently labeled with boron-dipyrromethene (BODIPY) for flow cytometry and immune fluorescence. In addition, the particles were loaded with a near-infrared dye (IR-Dye 780) for in vivo imaging. Using quantitative high performance liquid chromatography coupled with mass spectrometry, we determined the composition of the protein corona. Using these particles, we were able to demonstrate that the pattern of protein binding in the presence of serum correlates with the tendency to form aggregates in vitro and in vivo. In addition, the charge of the particles' surface influenced their uptake in phagocytes and endocytosis as well as their biodistribution after intravenous application in mice.

show abstract

Section: Discussionmentioning

confidence: 99%

Aggregation Behavior of Polystyrene-Nanoparticles in Human Blood Serum and its Impact on the in vivo Distribution in Mice

Mohr

Sommer²,

Baier

et al. 2014

J Nanomed Nanotechnol

View full text Add to dashboard Cite

show abstract

“…administration [17], the clearance and biodistribution of lipid nanocapsules following administration to the lungs has not been reported. Since lipid nanocapsules may be developed as drug carrier systems for the treatment of lung conditions which are likely to be accompanied by inflammation (e.g.…”

Section: Introductionmentioning

confidence: 99%

Lung inflammation does not affect the clearance kinetics of lipid nanocapsules following pulmonary administration

Patel

Woods

Riffo‐Vasquez

et al. 2016

Journal of Controlled Release

View full text Add to dashboard Cite

Lipid nanocapsules (LNCs) are semi-rigid spherical capsules with a triglyceride core that present a promising formulation option for the pulmonary delivery of drugs with poor aqueous solubility. Whilst the biodistribution of LNCs of different size has been studied following intravenous administration, the fate of LNCs following pulmonary delivery has not been reported. We investigated quantitatively whether lung inflammation affects the clearance of 50 nm lipid nanocapsules, or is exacerbated by their pulmonary administration. Studies were conducted in mice with lipopolysaccharide-induced lung inflammation compared to healthy controls. Particle deposition and nanocapsule clearance kinetics were measured by single photon emission computed tomography/computed tomography (SPECT/CT) imaging over 48 h. A significantly lower lung dose of 111 In-LNC50 was achieved in the lipopolysaccharide (LPS)-treated animals compared with healthy controls (p < 0.001). When normalised to the delivered lung dose, the clearance kinetics of 111 In-LNC50 from the lungs fit a first order model with an elimination half-life of 10.5 ± 0.9 h (R 2 = 0.995) and 10.6 ± 0.3 h (R 2 = 1.000) for healthy and inflamed lungs respectively (n = 3). In contrast, 111 In-diethylene triamine pentaacetic acid (DTPA), a small hydrophilic molecule, was cleared rapidly from the lungs with the majority of the dose absorbed within 20 min of administration. Biodistribution to lungs, stomach-intestine, liver, trachea-throat and blood at the end of the imaging period was unaltered by lung inflammation. This study demonstrated that lung clearance and whole body distribution of lipid nanocapsules were unaffected by the presence of acute lung inflammation.

show abstract

“…In the present study, DiD and Dil were used as probes because of their stability in LNCs, as has been previously observed in vivo and in vitro. 43 In the concentration range used, DiI and DiD brought a positive charge to the nanocapsules. It was relevant to use small nanocapsule quantities in mucus to study their stability in worst-case conditions, and thus we had to encapsulate a high amount of dyes, which unfortunately had an effect on the charge.…”

mentioning

confidence: 99%

“…6 The increase of particle size from 25 to 100 nm increased complement activation. 43 However, 25 nm LNCs quickly disappeared from the blood circulation. 46 As a consequence, 55 nm LNCs were chosen for diffusion studies in a function of their concentration.…”

mentioning

confidence: 99%

Fate of paclitaxel lipid nanocapsules in intestinal mucus in view of their oral delivery

Groo¹,

Saulnier²,

Gimel³

et al. 2013

IJN

Self Cite

View full text Add to dashboard Cite

The bioavailability of paclitaxel (Ptx) has previously been improved via its encapsulation in lipid nanocapsules (LNCs). In this work, the interactions between LNCs and intestinal mucus are studied because they are viewed as an important barrier to successful oral delivery. The rheological properties of different batches of pig intestinal mucus were studied under different conditions (the effect of hydration and the presence of LNCs). Fluorescence resonance energy transfer (FRET) was used to study the stability of LNCs in mucus at 37°C for at least 3 hours. Diffusion through 223, 446, and 893 μm mucus layers of 8.4, 16.8, and 42 μg/mL Ptx formulated as Taxol® (Bristol-Myers Squibb, Rueil-Malmaison, France) or encapsulated in LNCs (Ptx-LNCs) were investigated. The effect of the size of the LNCs on their diffusion was also investigated (range, 25–110 nm in diameter). Mucus behaves as a non-Newtonian gel with rheofluidifying properties and a flow threshold. The viscous (G″) and elastic (G′) moduli and flow threshold of the two mucus batches varied with water content, but G′ remained below G″. LNCs had no effect on mucus viscosity and flow threshold. The FRET efficiency remained at 78% after 3 hours. Because the destruction of the LNCs would lead to a FRET efficiency below 25%, these results suggest only a slight modification of LNCs after their contact with mucus. The diffusion of Taxol® and Ptx-LNCs in mucus decreases if the mucus layer is thicker. Interestingly, the apparent permeability across mucus is higher for Ptx-LNCs than for Taxol® for drug concentrations of 16.8 and 42 μg/mL Ptx ( P <0.05). The diffusion of Ptx-LNCs through mucus is not size-dependent. This study shows that LNCs are stable in mucus, do not change mucus rheological properties, and improve Ptx diffusion at low concentrations, thus making these systems good candidates for Ptx oral delivery. The study of the physicochemical interaction between the LNC surface and its diffusion in mucus is now envisioned.

show abstract

Influence of size, surface coating and fine chemical composition on the in vitro reactivity and in vivo biodistribution of lipid nanocapsules versus lipid nanoemulsions in cancer models

Cited by 69 publications

References 42 publications

Aggregation Behavior of Polystyrene-Nanoparticles in Human Blood Serum and its Impact on the in vivo Distribution in Mice

Aggregation Behavior of Polystyrene-Nanoparticles in Human Blood Serum and its Impact on the in vivo Distribution in Mice

Lung inflammation does not affect the clearance kinetics of lipid nanocapsules following pulmonary administration

Fate of paclitaxel lipid nanocapsules in intestinal mucus in view of their oral delivery

Contact Info

Product

Resources

About