RESUMO
This work pledge to extend the therapeutic windows of hybrid nanoparticulate systems by engineering mannose-decorated hybrid nanoparticles based on poly lactic-co-glycolic acid (PLGA) and vegetable oil for efficient delivery of two lipophilic anti-inflammatory therapeutics (Celecoxib-CL and Indomethacin-IMC) to macrophages. The mannose surface modification of nanoparticles is achieved via O-palmitoyl-mannose spacer during the emulsification and nanoparticles assembly process. The impact of targeting motif on the hydrodynamic features (RH, PdI), stability (ζ-potential), drug encapsulation efficiency (DEE) is thoroughly investigated. Besides, the in vitro biocompatibility (MTT, LDH) and susceptibility of mannose-decorated formulations to macrophage as well their immunomodulatory activity (ELISA) are also evaluated. The monomodal distributed mannose-decorated nanoparticles are in the range of nanometric size (RH < 115 nm) with PdI < 0.20 and good encapsulation efficiency (DEE = 46.15% for CL and 76.20% for IMC). The quantitative investigation of macrophage uptake shows a 2-fold increase in fluorescence (RFU) of cells treated with mannose-decorated formulations as compared to non-decorated ones (p < 0.001) suggesting an enhanced cell uptake respectively improved macrophage targeting while the results of ELISA experiments suggest the potential immunomodulatory properties of the designed mannose-decorated hybrid formulations.
Assuntos
Manose , Nanopartículas , Anti-Inflamatórios/farmacologia , Portadores de Fármacos , Glicóis , Macrófagos , Tamanho da Partícula , Óleos de PlantasRESUMO
The present study investigated the possibility of obtaining 3D printed composite constructs using biomaterial-based nanocomposite inks. The biopolymeric matrix consisted of methacrylated gelatin (GelMA). Several types of nanoclay were added as the inorganic component. Our aim was to investigate the influence of clay type on the rheological behavior of ink formulations and to determine the morphological and structural properties of the resulting crosslinked hydrogel-based nanomaterials. Moreover, through the inclusion of nanoclays, our goal was to improve the printability and shape fidelity of nanocomposite scaffolds. The viscosity of all ink formulations was greater in the presence of inorganic nanoparticles as shear thinning occurred with increased shear rate. Hydrogel nanocomposites presented predominantly elastic rather than viscous behavior as the materials were crosslinked which led to improved mechanical properties. The inclusion of nanoclays in the biopolymeric matrix limited hydrogel swelling due the physical barrier effect but also because of the supplementary crosslinks induced by the clay layers. The distribution of inorganic filler within the GelMA-based hydrogels led to higher porosities as a consequence of their interaction with the biopolymeric ink. The present study could be useful for the development of soft nanomaterials foreseen for the additive manufacturing of customized implants for tissue engineering.
RESUMO
The assessment of several ink formulations for 3D printing based on two natural macromolecular compounds is presented. In the current research we have exploited the fast crosslinking potential of pectin and the remarkable shear-thinning properties of carboxylated cellulose nanofibrils, which is known to induce a desired viscoelastic behavior. Prior to 3D printing, the viscoelastic properties of the polysaccharide inks were evaluated by rheological measurements and injectability tests. The reliance of the printing parameters on the ink composition was established through one-dimensional lines printing, the base units of 3D-structures. The performance of the 3D-printed structures after ionic cross-linking was evaluated in terms of mechanical properties and rehydration behavior. MicroCT was also used to evaluate the morphology of the 3D-printed objects regarding the effect of pectin/nanocellulose ratio on the geometrical features of scaffolds. The proportionality between the two polymers proved to be the determining factor for the firmness and strength of the printed objects.
Assuntos
Celulose/análogos & derivados , Tinta , Nanofibras/química , Pectinas/química , Impressão Tridimensional , Materiais Biocompatíveis/química , Hidrogéis/química , Reologia , Engenharia Tecidual , Alicerces Teciduais/químicaRESUMO
The aim of this study was to address one of the major challenges of the actual era of nanomedicine namely, the bioavailability of poorly water soluble drugs such as Silymarin. We developed new, biodegradable, and biocompatible nanosized shuttles for Silymarin targeted delivery in colon-cancer cells. The design of these 100 nm sized carrier nanoparticles was based on natural polymers and their biological properties such as cellular uptake potential, cytotoxicity and 3D penetrability were tested using a colon cancer cell line (HT-29) as the in vitro culture model. Comparative scanning electron microscopy (SEM) and atomic force microscopy (AFM) measurements demonstrated that the Silymarin loaded Poly(3-HydroxyButyrate-co-3-HydroxyValerate) (PHBHV) nanocarriers significantly decreased HT-29 cells viability after 6 and 24 h of treatment. Moreover, in vivo-like toxicity studies on multicellular tumor spheroids showed that the Silymarin loaded PHBHV nanocarriers are able to penetrate 3D micro tumors and significantly reduce their size.