International audienceLipid nanoparticles, based on nanoemulsion templates, are interesting candidates for contrast agent and active ingredient transport and delivery due to their small size, biodegradable nature and high versatility. An optimized nanosystem for drug delivery should present an important encapsulation ratio, as well as controlled release kinetics. In this context, the influence of the lipid nanoparticle core composition on the encapsulation and release behavior of the Nile Red fluorophore, used as a model molecule of intermediate lipophilicity, is explored. For that purpose, the lipid nanoparticle physical state, the encapsulated molecule localization, and the encapsulation/release behavior are studied. Careful characterization of lipid nanoparticles is performed by DSC and 1H NMR analysis. Nile Red localization is evaluated by complementary fluorescence spectroscopy and 1H NMR techniques. The encapsulation of Nile Red is governed and limited by its solubility in the lipids. A double localization of the fluorophore at the membrane and in the particle core is observed, resulting in a two-phase release kinetics: a quick burst release, followed by a slow prolonged release. Adding wax to the formulation increases the lipid nanoparticle internal viscosity while favoring Nile Red localization in the core, which results in slower release kinetics
Pulse radiolysis is used to determine the absorption spectra of
the transient species formed during the decay
of the hydrated electron in an aqueous solution of
AgI
1(NH3)2
+.
The absorption spectrum attributed to
Ag0
1(NH3)2
presents three peaks at 345, 385, and 435 nm. A theoretical
estimation of the redox potential of
the couple
AgI
1(NH3)2
+/Ag0
1(NH3)2
yields the value −2.4 VNHE. This value is consistent
with the fact that
AgI
1(NH3)2
+
is not directly reduced by
(CH3)2ĊO- and shows that
the redox potential of the silver monomer
couple is lowered by ammonia ligands.
The development of drug nanocarriers based on polymeric, lipid and ceramic biomaterials has been paving the way to precision medicine, where the delivery of poorly soluble active compounds and personalized doses are made possible. However, the nano-size character of these carriers has been demonstrated to have the potential to elicit pathways of the host response different from those of the same biomaterials when engineered as larger size implants and of the drugs when administered without a carrier. Therefore, a specific regulatory framework needs to be made available that can offer robust scientific insights and provide safety data by reliable tests of these novel nano-devices. In this context, the present work presents a multistep protocol for the in vitro assessment of the hemocompatibility of nanocarriers of different physicochemical properties. Poly (ethyl butyl cyanoacrylate) nanoparticles and lipid-based (LipImage™ 815) nanoparticles of comparable hydrodynamic diameter were tested through a battery of assays using human peripheral blood samples and recapitulating the main pathways of the host response upon systemic administration; i.e., protein interactions, fibrinogen-platelet binding, cytotoxicity, and inflammatory response. The data showed the sensitivity and reproducibility of the methods adopted that were also demonstrated to determine individual variability as well as to discriminate between activation of pathways of inflammation and unintended release of inflammatory signaling caused by loss of cell integrity. Therefore, this multistep testing is proposed as a reliable protocol for nanoparticle development and emerging regulatory frameworks.
Graphical abstract
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