that progressively affects cartilage, synovial membranes, subchondral bone, and periarticular tissues. The risk factors of OA include age, gender, joint biomechanics, genetic factors, and adiposity. Due to the localized nature of the disease, intraarticular (IA) drug injection [4][5][6][7] is an attractive treatment approach. IA administrations may show an improved benefitrisk ratio by increasing the dose efficacy at the site of action and minimizing the risks of systemic adverse effects, drugdrug interactions, and other toxicities, specifically when the drug stays locally at the site of injection. Various formulations of hyaluronic acid and corticosteroids are approved by the Food and Drug Administration [8] and currently commercially available for OA IA treatments; however, they only provide symptomatic pain relief and do not modify disease progression. Recently, kartogenin (KGN), a CBFβ-RUNX1 pathway activator, has been reported as a promising active pharmaceutical ingredient (API) for articular cartilage regeneration and protection. [9,10] This small molecule is a disease-modifying OA drug (DMOAD) that is able to activate the transcription of proteins that lead to the chondrocyte differentiation of primary human mesenchymal stem cells (EC 50 value 100 × 10 −9 m). [9,11] There is a high medical need to develop drug delivery systems specifically suited for the IA environment to avoid the An efficient treatment for osteoarthritis (OA) can benefit from the local release of a high therapeutic dose over an extended period of time. Such a treatment will minimize systemic side effects and avoid the inconvenience of frequent injections. To this aim, nanocrystal-polymer particles (NPPs) are developed by combining the advantages of nanotechnology and microparticles. Nanocrystals are produced by wet milling kartogenin (KGN), which is known to promote chondrogenesis and to foster chondroprotection. A fluorescent biodegradable polymer is synthesized for intravital particle tracking. Polymer microparticles with 320 nm embedded KGN nanocrystals (KGN-NPPs) show a high drug loading of 31.5% (w/w) and an extended drug release of 62% over 3 months. In vitro, these particles do not alter mitochondrial activity in cultured human OA synoviocytes. In vivo, KGN-NPPs demonstrate higher bioactivity than a KGN solution in a murine mechanistic OA model based on histological assessment (Osteoarthritis Research Society International score), epiphyseal thickness (microcomputed tomography), OA biomarkers (e.g., vascular endothelial growth factor, Adamts5), and prolonged intraarticular persistence (fluorescence analysis). This work provides proof-ofconcept of a novel and innovative extended drug delivery system with the potential to treat human OA. Osteoarthritis TherapyThe ORCID identification number(s) for the author(s) of this article can be found under https://doi

Amphiphilic molecules-molecules that have both hydrophobic and hydrophilic properties-can self-assemble in water to form diverse structures such as micelles, vesicles and tubes, and these nanostructures can be used for delivering drugs, stabilizing membrane proteins or as nanoreactors. We have previously shown that lipids can self-organize on the surface of single-walled carbon nanotubes into regular ring-shaped assemblies. Here we show that these lipid assemblies can be polymerized and isolated from the nanotube template by application of an electric field. We also demonstrate that these assemblies are monodispersed, water-soluble, and can dissolve various hydrophobic rylene dyes, fullerenes and membrane proteins. The stability of these constructs and their diverse applications will be useful in the fields of cosmetics, medicine and material sciences.

A B S T R A C TSmall-molecule agonists for the Toll-like receptors (TLR) 7 and 8 are effective for the immunotherapy of skin cancer when used as topical agents. Their systemic use has however been largely unsuccessful due to doselimiting toxicity. We propose a polymer-based nanodelivery system to target resiquimod, a TLR7 ligand, to the lymph node in order to focus the immunostimulatory activity and to prevent a generalized inflammatory response. We demonstrate successful encapsulation of resiquimod in methoxypoly(ethylene glycol)-b-poly(DLlactic acid) (mPEG-PLA) and mixed poly(DL-lactic-co-glycolic acid) (PLGA)/mPEG-PLA nanoparticles. We show that these particles are taken up mainly by dendritic cells and macrophages, which are the prime initiators of anticancer immune responses. Nanoparticles loaded with resiquimod activate these cells, demonstrating the availability of the immune-stimulating cargo. The unloaded particles are non-inflammatory and do not have cytotoxic activity on immune cells. Following subcutaneous injection in mice, mPEG-PLA and PLGA/mPEG-PLA nanoparticles are detected in dendritic cells and macrophages in the draining lymph nodes, demonstrating the targeting potential of these particles. Thus, polymer-based nanoparticles represent a promising delivery system that allows lymph node targeting for small-molecule TLR7 agonists in the context of systemic cancer immunotherapy.