Thermosensitive In Situ Gelling Poloxamers/Hyaluronic Acid Gels for Hydrocortisone Ocular Delivery.

This study endeavored to overcome the physiological barriers hindering optimal bioavailability in ophthalmic therapeutics by devising drug delivery platforms that allow therapeutically effective drug concentrations in ocular tissues for prolonged times. Thermosensitive drug delivery platforms were formulated by blending poloxamers (F68 and F127) with low-molecular-weight hyaluronic acid (HA) in various concentrations and loaded with hydrocortisone (HC). Among the formulations examined, only three were deemed suitable based on their desirable gelling properties at a temperature close to the eye's surface conditions while also ensuring minimal gelation time for swift ocular application. Rheological analyses unveiled the ability of the formulations to develop gels at suitable temperatures, elucidating the gel-like characteristics around the physiological temperature essential for sustained drug release. The differential scanning calorimetry findings elucidated intricate hydrogel-water interactions, indicating that HA affects the water-polymer interactions within the gel by increasing the platform hydrophilicity. Also, in vitro drug release studies demonstrated significant hydrocortisone release within 8 h, governed by an anomalous transport mechanism, prompting further investigation for optimized release kinetics. The produced platforms offer promising prospects for efficacious ocular drug delivery, addressing pivotal challenges in ocular therapeutics and heralding future advancements in the domain.

Investigating the Effect of Surface Hydrophilicity on the Destiny of PLGA-Poloxamer Nanoparticles in an In Vivo Animal Model.

This study aimed to examine the impact of different surface properties of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (P NPs) and PLGA-Poloxamer nanoparticles (PP NPs) on their in vivo biodistribution. For this purpose, NPs were formulated via nanoprecipitation and loaded with diphenylhexatriene (DPH), a fluorescent dye. The obtained NPs underwent comprehensive characterization, encompassing their morphology, technological attributes, DPH release rate, and thermodynamic properties. The produced NPs were then administered to wild-type mice via intraperitoneal injection, and, at scheduled time intervals, the animals were euthanized. Blood samples, as well as the liver, lungs, and kidneys, were extracted for histological examination and biodistribution analysis. The findings of this investigation revealed that the presence of poloxamers led to smaller NP sizes and induced partial crystallinity in the NPs. The biodistribution and histological results from in vivo experiments evidenced that both, P and PP NPs, exhibited comparable concentrations in the bloodstream, while P NPs could not be detected in the other organs examined. Conversely, PP NPs were primarily sequestered by the lungs and, to a lesser extent, by the kidneys. Future research endeavors will focus on investigating the behavior of drug-loaded NPs in pathological animal models.

Fluorescent nanodiamonds as innovative delivery systems for MiR-34a replacement in breast cancer.

Nanodiamonds are innovative nanocrystalline carbon particles able to deliver chemically conjugated miRNAs. In oncology, the use of miRNA-based therapies may represent an advantage, based on their ability to simultaneously target multiple intracellular oncogenic targets. Here, nanodiamonds were tested and optimized to deliver miR-34a, a miRNA playing a key role in inhibiting tumor development and progression in many cancers. The physical-chemical properties of nanodiamonds were investigated suggesting electrical stability and uniformity of structure and size. Moreover, we evaluated nanodiamond cytotoxicity on two breast cancer cell models and confirmed their excellent biocompatibility. Subsequently, nanodiamonds were conjugated with miR-34a, using the chemical crosslinker polyethyleneimine; real-time PCR analysis revealed a higher level of miR-34a in cancer cells treated with the different formulations of nanodiamonds than with commercial transfectant. A significant and early nanodiamond-miR-34a uptake was recorded by FACS and fluorescence microscopy analysis in MCF7 and MDA-MB-231 cells. Moreover, nanodiamond-miR-34a significantly inhibited both cell proliferation and migration. Finally, a remarkable anti-tumor effect of miR-34a-conjugated nanodiamonds was observed in both heterotopic and orthotopic murine xenograft models. In conclusion, this study provides a rationale for the development of new therapeutic strategies based on use of miR-34a delivered by nanodiamonds to improve the clinical treatment of neoplasms.

Cerium-Doped Self-Assembling Nanoparticles as a Novel Anti-Oxidant Delivery System Preserving Mitochondrial Function in Cortical Neurons Exposed to Ischemia-like Conditions.

Neurodegenerative diseases are characterized by mitochondrial dysfunction leading to abnormal levels of reactive oxygen species (ROS), making the use of ROS-scavenging nanomaterials a promising therapeutic approach. Here, we combined the unique ROS-scavenging properties of cerium-based nanomaterials with the lipid self-assembling nanoparticles (SANP) technology. We optimized the preparation of cerium-doped SANP (Ce-SANP) and characterized the formulations in terms of both physiochemical and biological properties. Ce-SANP exhibited good colloidal properties and were able to mimic the activity of two ROS-scavenging enzymes, namely peroxidase and super oxide dismutase. Under ischemia-like conditions, Ce-SANP could rescue neuronal cells from mitochondrial suffering by reducing ROS production and preventing ATP level reduction. Furthermore, Ce-SANP prevented mitochondrial Ca2+ homeostasis dysfunction, partially restoring mitochondrial Ca2+ handling. Taken together, these results highlight the potential of the anti-oxidant Ce-SANP platform technology to manage ROS levels and mitochondrial function for the treatment of neurodegenerative diseases.

Structural concretes with waste-based lightweight aggregates: from landfill to engineered materials.

This research provides possible opportunities in the reuse of waste and particularly muds, coming from both ornamental stone (granite sludges from sawing and polishing operations) and ceramic production (porcelain stoneware tile polishing sludge), for the manufacture of lightweight aggregates. Lab simulation of the manufacturing cycle was performed by pelletizing and firing the waste mixes in a rotative furnace up to 1300 degrees C, and determining composition and physicomechanical properties of lightweight aggregates. The best formulation was used to produce and test lightweight structural concretes according to standard procedures. Both granite and porcelain stoneware polishing sludges exhibit a suitable firing behavior due to the occurrence of SiC (an abrasive component) which, by decomposing at high temperature with gas release, acts as a bloating promoter, resulting in aggregates with particle density < 1 Mg/m3. However, slight variations of mixture composition produce aggregates with rather different properties, going from values close to those of typical commercial expanded clays (particle density 0.68 Mg/m3; strength of particle 1.2 MPa) to products with high mechanical features (particle density 1.25 Mg/m3; strength of particle 6.9 MPa). The best formulation (50 wt.% porcelain stoneware polishing sludge +50 wt.% granite sawing sludge) was used to successfully manufacture lightweight structural concretes with suitable properties (compressive strength 28 days > 20 MPa, bulk density 1.4-2.0 Mg/m3).