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Sinomenine (SIN), a natural product, has been used to treat rheumatoid arthritis (RA) in China for thousands of years. SIN has been developed for the treatment of RA by way of tablets and injections, but both dosage forms have been associated with severe adverse reactions. Making SIN into liposomes-in-hydrogel biomaterials for external use has a good slow-release effect and can play an important role in avoiding the first-pass effect, gastrointestinal reaction, and increasing the local action time of drugs. SIN-loaded liposomes were formed by the thin-film dispersion method, then SIN-loaded liposomes-in-hydrogels were prepared by combining the SIN-L with hyaluronic acid (HA) hydrogels. In this paper, the basic characteristics, In vitro and Ex vivo release, and antioxidant activity of SIN-loaded liposomes-in-hydrogels were studied. The results showed that SIN-loaded liposomes-in-hydrogels have good sustained-release and antioxidant effects, and the preparation is expected to be a good biomaterial. [ABSTRACT FROM AUTHOR]

Background: Standard chemotherapy with taxanes, such as paclitaxel (PTX), remains the mainstay of systemic treatment of triple-negative breast cancer. Nanotechnology-based formulations have gradually replaced PTX injection and are widely used in China. However, no studies have compared the colloidal stability, antitumor efficacy, and safety of commercial PTX nanoformulations. Additionally, the desire to evaluate preclinical antitumor efficacy in human-derived tumor cells led to the widespread application of immunodeficient mouse models that likely contributed to the neglect of nanomedicines-immune system interactions. The present study investigated the colloidal stability, antitumor efficacy and safety, and nanomedicines-host immune system interactions of PTX nanoformulations. A further comparative analysis was performed to evaluate the clinical potential. Results: Compared with liposome, PTX emulsion and PTX nanoparticle exhibited favorable colloidal stability. PTX emulsion was superior in inducing apoptosis and had a more pronounced inhibitory effect on 4T1-tumor spheroids compared with PTX liposome and PTX nanoparticle. Although PTX emulsion exhibited superior in vitro antitumor effect, no significant differences in the in vivo antitumor efficacy were found among the three types of PTX nanoformulations in an immunocompetent orthotopic 4T1 murine triple-negative breast cancer model. All PTX nanoformulations at maximum tolerated dose (MTD) induced lymphopenia and immunosuppression, as evidenced by the reduction of T cell subpopulations and inhibition of the dendritic cells maturation. Conclusions: The MTD PTX nanomedicines-induced lymphopenia and immunosuppression may weaken the lymphocyte-mediated antitumor cellular immune response and partly account for the lack of differences in the in vivo antitumor outcomes of PTX nanoformulations. Understanding of what impacts PTX nanomedicines has on the immune system may be critical to improve the design and conduct of translational research of PTX nanomedicines in monotherapy or combination therapy with immunotherapy. [ABSTRACT FROM AUTHOR]

AL3810, a molecular dual inhibitor of the vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), has earned the permission of phase II clinical trial for tumor treatment by China FDA. As a reversible ATP-competitive inhibitor, AL3810 targets ATP-binding site on intracellular region of VEGFR and FGFR, whereas, AL3810 lacking interplay with extracellular region of receptors rendered deficient blood–brain tumor barrier (BBTB) recognition, poor brain penetration and unsatisfactory anti-glioma efficacy. Integrin α v β 3 overexpressed on capillary endothelial cells of BBTB as well as glioma cells illuminated ligand-modified liposomes for pinpoint spatial delivery into glioma. The widely accepted peptide c(RGDyK)-modified liposome loading AL3810 of multiple dosing caused hypothermia, activated anti-c(RGDyK)-liposome IgG and IgM antibody and pertinent complements C3b and C5b-9, and experienced complement-dependent opsonization. We newly proposed a pentapeptide mn with superb α v β 3-binding affinity and tailored AL3810-loaded mn-modified liposome that afforded impervious blood circulation, targeting ability, and glioma therapeutic expertise as vastly alleviated immune opsonization on the underpinning of the finite antibodies and complements assembly. Stemming from attenuated immunogenicity, peptide mn strengthened liposome functions as a promising nanocarrier platform for molecular targeting agents. Compared with c(RGDyK)-liposome, α v β 3-targeted mn-liposome abated the opsonic effect as lower anti-liposome IgG and IgM antibody titer, less complements activation and subsequently less phagocytosis by macrophages. Stemming from attenuated immunogenicity, mn-liposome successfully realized AL3810 delivery for glioma-targeted therapy. Image 1 [ABSTRACT FROM AUTHOR]