RESUMEN
Elasticity of polymer microcapsules (MCs) filled with a liquid fluorinated core is studied by atomic force microscopy (AFM). Accurately characterized spherical tips are employed to obtain the Young's moduli of MCs having four different shell thicknesses. We show that those moduli are effective ones because the samples are composites. The strong decrease of the effective MC elasticity (from 3.0 to 0.1 GPa) as the shell thickness decreases (from 200 to 10 nm) is analyzed using a novel numerical approach. This model describes the evolution of the elasticity of a coated half-space according to the contact radius, the thickness of the film, and the elastic moduli of bulk materials. This numerical model is consistent with the experimental data and allows simulating the elastic behavior of MCs at high frequencies (5 MHz). While the quasi-static elasticity of the MCs is found to be very dependent on the shell thickness, the high frequency (5 MHz) elastic behavior of the core leads to a stable behavior of the MCs (from 2.5 to 3 GPa according to the shell thickness). Finally, the effect of thermal annealing on the MCs elasticity is investigated. The Young's modulus is found to decrease because of the reduction of the shell thickness due to the loss of the polymer.
RESUMEN
In the context of growing use of nanoparticles, it is important to be able to characterize all their physical properties in order to understand their behavior, to optimize them, and to control their quality. We showed that ultrasonic spectroscopy provides many of the desired properties. To do so, we used as an example nanocapsules made of a polymer shell encaspulating a liquid perfluorocarbon core and designed them for theranostic applications. Frequency-dependent measurements of both ultrasound velocity and attenuation were performed on nanocapsule suspensions. Then the desired properties were extracted by analyzing the experimental data using a recently developed model that relates the speed of sound and attenuation of a suspension to the geometrical and viscoelastic properties of the nanocapsules.
Asunto(s)
Nanopartículas/química , Modelos Teóricos , Nanocápsulas/química , Nanomedicina Teranóstica , UltrasonidoRESUMEN
Most nanoparticles produced for drug delivery purposes are spherical. However, the literature suggests that elongated particles are advantageous, notably in terms of cellular uptake. Thus, we synthesized biocompatible polylactide-b-poly(ethylene glycol) (PLA-PEG) polymers bearing carboxylate moieties, and used them to formulate worm-like nanoparticles by a simple emulsion-evaporation process. Worm-like nanoparticles with variable aspect ratio were obtained by simply adjusting the molar mass of the PLA block: the shorter the molar mass of the PLA block, the more elongated the particles. As PLA molar mass decreased from 80,000 g/mol to 13,000 g/mol, the proportion of worm-like nanoparticles increased from 0 to 46%, in contradiction with the usual behavior of block polymers based on their packing parameter. To explain this unusual phenomenon, we hypothesized the shape arises from a combination of steric and electrostatic repulsions between PEG chains bearing a carboxylate moiety present at the dichloromethane-water interface during the evaporation process. Worm-like particles turned out to be unstable when incubated at 37 °C, above polymer glass transition temperature. Indeed, above Tg, a Plateau-Rayleigh instability occurs, leading to the division of the worm-like particles into spheres. However, this instability was slow enough to assess worm-like particles uptake by murine macrophages. A slight but significant increase of internalization was observed for worm-like particles, compared to their spherical counterparts, confirming the interest of developing biocompatible anisotropic nanoparticles for pharmaceutical applications such as drug delivery.
Asunto(s)
Nanopartículas , Polímeros , Ratones , Animales , Polietilenglicoles , Poliésteres , Sistemas de Liberación de Medicamentos , Tamaño de la PartículaRESUMEN
Targeted delivery of dexamethasone to inflamed tissues using nanoparticles is much-needed to improve its efficacy while reducing side effects. To drastically improve dexamethasone loading and prevent burst release once injected intravenously, a lipophilic prodrug dexamethasone palmitate (DXP) was encapsulated into poly(DL-lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs). DXP-loaded PLGA-PEG NPs (DXP-NPs) of about 150 nm with a drug loading as high as 7.5% exhibited low hemolytic profile and cytotoxicity. DXP-NPs were able to inhibit the LPS-induced release of inflammatory cytokines in macrophages. After an intravenous injection to mice, dexamethasone (DXM) pharmacokinetic profile was also significantly improved. The concentration of DXM in the plasma of healthy mice remained high up to 18 h, much longer than the commercial soluble drug dexamethasone phosphate (DSP). Biodistribution studies showed lower DXM concentrations in the liver, kidneys, and lungs when DXP-NPs were administered as compared with the soluble drug. Histology analysis revealed an improvement in the knee structure and reduction of cell infiltration in animals treated with the encapsulated DXP compared with the soluble DSP or non-treated animals. In summary, the encapsulation of a lipidic prodrug of dexamethasone into PLGA-PEG NPs appears as a promising strategy to improve the pharmacological profile and reduce joint inflammation in a murine model of rheumatoid arthritis.
Asunto(s)
Artritis , Nanopartículas , Profármacos , Animales , Dexametasona , Portadores de Fármacos/química , Ratones , Nanopartículas/química , Tamaño de la Partícula , Polietilenglicoles/química , Distribución TisularRESUMEN
Among cardiovascular diseases, atherosclerosis remains the first cause of death in the United States of America and Europe, as it leads to myocardial infarction or stroke. The high prevalence of heart diseases is due to the difficulty in diagnosing atherosclerosis, since it can develop for decades before symptoms occur, and to the complexity of the treatment since targets are also important components of the host defenses. The antidiabetics thiazolidinediones, among which is rosiglitazone (RSG), have demonstrated anti-atherosclerotic effect in animal models, and are therefore promising candidates for the improvement of atherosclerosis management. Nevertheless, their administration is hindered by the insurgence of severe side effects. To overcome this limitation, rosiglitazone has been encapsulated into polymeric nanoparticles, which permit efficient delivery to its nuclear target, and selective delivery to the site of action, allowing the reduction of unwanted effects. In the present work, we describe nanoparticle formulation using polylactic acid (PLA) coupled to polyethylene glycol (PEG), their characterization, and their behavior on RAW264.7 macrophages, an important target in atherosclerosis treatment. RSG nanocarriers showed no toxicity on cells at all concentrations tested, an anti-inflammatory effect in a dose-dependent manner, up to 5 times more efficient than the free molecule, and an increased RSG uptake which is consistent with the effect shown. These biodegradable nanoparticles represent a valid tool to be further investigated for the treatment of atherosclerosis.