calixarenes and Disease-Models--Animal

Excessive inflammatory reaction aggravates brain injury and hinders the recovery of neural function in nervous system diseases. Microglia, as the major players of neuroinflammation, control the progress of the disease. There is an urgent need for effective non-invasive therapy to treat neuroinflammation mediated by microglia. However, the lack of specificity of anti-inflammatory agents and insufficient drug dose penetrating into the brain lesion area are the main problems. Here, we evaluated a series of calixarenes and found that among them the self-assembling architecture of amphiphilic sulfonatocalix[8]arene (SC8A12C) had the most potent ability to suppress neuroinflammation in vitro and in vivo. Moreover, SC8A12C assemblies were internalized into microglia through macropinocytosis. In addition, after applying the SC8A12C assemblies to the exposed brain tissue, we observed that SC8A12C assemblies penetrated into the brain parenchyma and eliminated the inflammatory factor storm, thereby restoring neurobiological functions in a mouse model of traumatic brain injury.

Topics: Animals; Brain Injuries, Traumatic; Calixarenes; Disease Models, Animal; Inflammation; Mice; Mice, Inbred C57BL; Microglia; Neuroinflammatory Diseases

Primary intracerebral hemorrhage (ICH) is a leading cause of long-term disability and death worldwide. Drug delivery vehicles to treat ICH are less than satisfactory because of their short circulation lives, lack of specific targeting to the hemorrhagic site, and poor control of drug release. To exploit the fact that metal ions such as Fe

Topics: Animals; Benzylisoquinolines; Blood-Brain Barrier; Calixarenes; Cerebral Hemorrhage; Disease Models, Animal; Drug Carriers; Humans; Interleukin-1beta; Ions; Male; Matrix Metalloproteinase 9; Metals; Mice; Mice, Inbred C57BL; Nanostructures; Neurons; Neuroprotective Agents; Organophosphonates; Phenols; Reactive Oxygen Species; Tetrahydroisoquinolines

Curcumin (CUR) has shown remarkable efficacy in the treatment of skin diseases, but its effective transdermal delivery is still a major challenge and stimulates interest in the design of novel systems for CUR dispersion, preservation, and delivery facilitation to the deeper layers of the skin. The present work aimed to investigate the potential of a nanohydrogel, formed by a micellar choline-calix[4]arene amphiphile (CALIX) and CUR, in the treatment of skin diseases through an imiquimod (IMQ)-induced psoriasis model. Psoriasis plaques are associated with aberrant keratinization, abnormal distribution of tight junctions (TJs) proteins, and enhanced expression of inflammatory markers. The nanohydrogel restored the normal distribution of TJs proteins ZO1 and occludin and reduced the expression of TNF-α and inducible nitric oxide synthetase (iNOS) compared to the untreated IMQ group. The novelty lies in the calix[4]arene-based nanohydrogel as a potential new soft material for the topical skin delivery of CUR. The nanohydrogel, due to its physicochemical and mechanical properties, enhances the drug water-solubility, preserves CUR from rapid degradation, and eases the local skin administration and penetration.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Calixarenes; Choline; Curcumin; Disease Models, Animal; Drug Carriers; Hydrogels; Male; Mice; Mice, Inbred BALB C; Phenols; Psoriasis

The inhibition of angiogenesis is a promising avenue for cancer treatment. Although some angiostatic compounds are in the process of development and testing, these often prove ineffective in vivo or have unwanted side effects. We have designed, synthesized, and evaluated a small library of nonpeptidic, calixarene-based protein surface topomimetics that display chemical substituents to approximate the molecular dimensions and amphipathic features (hydrophobic and positively charged residues) of the antiangiogenic peptide anginex, which, like many antiangiogenic proteins, consists primarily of an antiparallel beta-sheet structure as the functional unit. Two of the topomimetics (0118 and 1097) were potent angiogenesis inhibitors in vitro, as determined by endothelial cell proliferation, migration, and chick embryo chorioallantoic membrane assays. Moreover, both compounds were highly effective at inhibiting tumor angiogenesis and growth in two mouse models (MA148 human ovarian carcinoma and B16 murine melanoma). Our results demonstrate the feasibility of designing nonpeptidic protein surface topomimetics as novel pharmaceutical agents for clinical intervention against cancer through angiostatic or other mechanisms.

Topics: Angiogenesis Inhibitors; Animals; Apoptosis; Calixarenes; Disease Models, Animal; Drug Design; Feasibility Studies; Female; Humans; Melanoma, Experimental; Mice; Ovarian Neoplasms; Peptides; Proteins