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Chronic inflammation contributes to the pathogenesis of many diseases, including apparently unrelated conditions such as metabolic disorders, cardiovascular diseases, neurodegenerative diseases, osteoporosis, and tumors, but the use of conventional anti-inflammatory drugs to treat these diseases is generally not very effective given their adverse effects. In addition, some alternative anti-inflammatory medications, such as many natural compounds, have scarce solubility and stability, which are associated with low bioavailability. Therefore, encapsulation within nanoparticles (NPs) may represent an effective strategy to enhance the pharmacological properties of these bioactive molecules, and poly lactic-co-glycolic acid (PLGA) NPs have been widely used because of their high biocompatibility and biodegradability and possibility to finely tune erosion time, hydrophilic/hydrophobic nature, and mechanical properties by acting on the polymer's composition and preparation technique. Many studies have been focused on the use of PLGA-NPs to deliver immunosuppressive treatments for autoimmune and allergic diseases or to elicit protective immune responses, such as in vaccination and cancer immunotherapy. By contrast, this review is focused on the use of PLGA NPs in preclinical in vivo models of other diseases in which a key role is played by chronic inflammation or unbalance between the protective and reparative phases of inflammation, with a particular focus on intestinal bowel disease; cardiovascular, neurodegenerative, osteoarticular, and ocular diseases; and wound healing. [ABSTRACT FROM AUTHOR]

The most important limitations of chemotherapeutic agents are severe side effects and the development of multi-drug resistance. Recently, the clinical successes achieved with immunotherapy have revolutionized the treatment of several advanced-stage malignancies, but most patients do not respond and many of them develop immune-related adverse events. Loading synergistic combinations of different anti-tumor drugs in nanocarriers may enhance their efficacy and reduce life-threatening toxicities. Thereafter, nanomedicines may synergize with pharmacological, immunological, and physical combined treatments, and should be increasingly integrated in multimodal combination therapy regimens. The goal of this manuscript is to provide better understanding and key considerations for developing new combined nanomedicines and nanotheranostics. We will clarify the potential of combined nanomedicine strategies that are designed to target different steps of the cancer growth as well as its microenvironment and immunity interactions. Moreover, we will describe relevant experiments in animal models and discuss issues raised by translation in the human setting. [ABSTRACT FROM AUTHOR]

This work presents a computational model to study the degradation behavior of polyester-based three-dimensional (3D) functionalized scaffolds for bone regeneration. As a case study, we investigated the behavior of a 3D-printed scaffold presenting a functionalized surface with ICOS-Fc, a bioactive protein able to stimulate bone regeneration and healing, inhibiting osteoclast activity. The aim of the model was to optimize the scaffold design to control its degradation and thus the release of grafted protein over time and space. Two different scenarios were considered: (i) a scaffold without macroporosity presenting a functionalized external surface; and (ii) a scaffold presenting an internal functionalized macroporous architecture with open channels to locally deliver the degradation products. [ABSTRACT FROM AUTHOR]

Conventional therapies for immune-mediated diseases, including autoimmune disorders, transplant reactions, and allergies, have undergone a radical evolution in the last few decades; however, they are still not specific enough to avoid widespread immunosuppression. The idea that vaccine usage could be extended beyond its traditional immunogenic function by encompassing the ability of vaccines to induce antigen-specific tolerance may revolutionize preventive and therapeutic strategies in several clinical fields that deal with immune-mediated disorders. This approach has been supported by improved data relating to the several mechanisms involved in controlling unwanted immune responses and allowing peripheral tolerance. Given these premises, several approaches have been developed to induce peripheral tolerance against the antigens that are involved in the pathological immune response, including allergens, autoantigens, and alloantigens. Technological innovations, such as nucleic acid manipulation and the advent of micro- and nanoparticles, have further supported these novel preventive and therapeutic approaches. This review focuses on the main strategies used in the development of tolerogenic vaccines, including the technological issues used in their design and the role of "inverse adjuvants". Even though most studies are still limited to the preclinical field, the enthusiasm generated by their results has prompted some initial clinical trials, and they show great promise for the future management of immune-mediated pathological conditions. [ABSTRACT FROM AUTHOR]