Intra-articular administration of anti-inflammatory drugs is a strategy that allows localized action on damaged articular cartilage and reduces the side effects associated with systemic drug administration. The objective of this work is to prepare injectable thermosensitive hydrogels for the long-term application of dexamethasone. The hydrogels were prepared by mixing chitosan (CS) and Pluronic-F127 (PF) physically. In addition, tripolyphosphate (TPP) was used as a crosslinking agent. Chitosan added to the mix increased the gel time compared to the pluronic gel alone. The incorporation of TPP into the material modified the morphology of the hydrogels formed. Subsequently, MTS and Live/Dead^® experiments were performed to investigate the toxicity of hydrogels against human chondrocytes. The in vitro releases of dexamethasone (DMT) from CS-PF and CS-PF-TPP gels had an initial burst and took more time than that from the PF hydrogel. In vivo studies showed that hydrogels retained the fluorescent compound longer in the joint than when administered in PBS alone. These results suggest that the CS-PF and CS-PF-TPP hydrogels loaded with DMT could be a promising drug delivery platform for the treatment of osteoarthritis.

Cancer has become one of the deadliest diseases in our society. Surgery accompanied by subsequent chemotherapy is the treatment most used to prolong or save the patient’s life. Still, it carries secondary risks such as infections and thrombosis and causes cytotoxic effects in healthy tissues. Using nanocarriers such as smart polymer micelles is a promising alternative to avoid or minimize these problems. These nanostructured systems will be able to encapsulate hydrophilic and hydrophobic drugs through modified copolymers with various functional groups such as carboxyls, amines, hydroxyls, etc. The release of the drug occurs due to the structural degradation of these copolymers when they are subjected to endogenous (pH, redox reactions, and enzymatic activity) and exogenous (temperature, ultrasound, light, magnetic and electric field) stimuli. We did a systematic review of the efficacy of smart polymeric micelles as nanocarriers for anticancer drugs (doxorubicin, paclitaxel, docetaxel, lapatinib, cisplatin, adriamycin, and curcumin). For this reason, we evaluate the influence of the synthesis methods and the physicochemical properties of these systems that subsequently allow an effective encapsulation and release of the drug. On the other hand, we demonstrate how computational chemistry will enable us to guide and optimize the design of these micelles to carry out better experimental work.

Nanoparticles (NPs) have a tremendous potential in medicinal applications, and recent studies have pushed the boundaries in nanotherapy, including in osteoarthritis treatments. The aim of this study was to develop new poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) surfaces decorated with hyaluronic acid (HA) to enhance targeted drug specificity to the osteoarthritic knee joint. HA was selected since it binds to specific receptors expressed in many cells, such as the cluster determinant 44 (CD44), a major receptor of chondrocytes, and because of its function in the synovial fluid (SF), such as maintenance of high fluid viscosity. The PLGA polymer was grafted to sodium hyaluronate using dimethoxy-PEG (PLGA-HA) and compared with control PLGA NPs (not grafted). NPs were characterized by 1H-NMR and IR spectroscopy. Then, near-infrared (NIR) dye and gold (20 nm) were encapsulated in the formulated NPs and used to access NPs’ performance in in vitro, in vivo, and ex vivo experiments. To test the NPs’ CD44 receptor specificity, an antibody assay was performed. All NPs presented a size in the range viable for cell-uptake, no cytotoxicity to chondrocytes was registered. Although all the NPs had a high capacity to be absorbed by the cells, PLGA-HA NPs showed significantly higher affinity towards the chondrocytic C28/I2 cell line. In conclusion, PLGA NPs grafted to sodium hyaluronate showed increased binding to cartilage cells and tissue and enhanced accumulation at the target site. Thus, this study presents a safe drug-delivery system with improved receptor specificity, which may represent an advantageous alternative to current nanotherapies.

Hydrogels obtained from combining different polymers are an interesting strategy for developing controlled release system platforms and tissue engineering scaffolds. In this study, the applicability of sodium alginate-g-(QCL-co-HEMA) hydrogels for these biomedical applications was evaluated. Hydrogels were synthesized by free-radical polymerization using a different concentration of the components. The hydrogels were characterized by Fourier transform-infrared spectroscopy, scanning electron microscopy, and a swelling degree. Betamethasone release as well as the in vitro cytocompatibility with chondrocytes and fibroblast cells were also evaluated. Scanning electron microscopy confirmed the porous surface morphology of the hydrogels in all cases. The swelling percent was determined at a different pH and was observed to be pH-sensitive. The controlled release behavior of betamethasone from the matrices was investigated in PBS media (pH = 7.4) and the drug was released in a controlled manner for up to 8 h. Human chondrocytes and fibroblasts were cultured on the hydrogels. The MTS assay showed that almost all hydrogels are cytocompatibles and an increase of proliferation in both cell types after one week of incubation was observed by the Live/Dead^® assay. These results demonstrate that these hydrogels are attractive materials for pharmaceutical and biomedical applications due to their characteristics, their release kinetics, and biocompatibility.

The intra-articular administration of drugs has attracted great interest in recent decades for the treatment of osteoarthritis. The use of modified drugs has also attracted interest in recent years because their intra-articular administration has demonstrated encouraging results. The objective of this work was to prepare injectable-thermosensitive hydrogels for the intra-articular administration of Etanercept (ETA), an inhibitor of tumor necrosis factor-α. Hydrogels were prepared from the physical mixture of chitosan and Pluronic F127 with β-glycerolphosphate (BGP). Adding β-glycerolphosphate to the system reduced the gelation time and also modified the morphology of the resulting material. In vitro studies were carried out to determine the cytocompatibility of the prepared hydrogels for the human chondrocyte line C28/I2. The in vitro release study showed that the incorporation of BGP into the system markedly modified the release of ETA. In the in vivo studies, it was verified that the hydrogels remained inside the implantation site in the joint until the end of the study. Furthermore, ETA was highly concentrated in the blood of the study mice 48 h after the loaded material was injected. Histological investigation of osteoarthritic knees showed that the material promotes cartilage recovery in osteoarthritic mice. The results demonstrate the potential of ETA-loaded injectable hydrogels for the localized treatment of joints.