Heparin is a potent anticoagulant agent that interacts strongly with antithrombin III to prevent the formation of fibrin clots. In the present work, poly(dimethylsiloxane)(PDMS)/graphite oxide–benzalkonium chloride–heparin (PDMS/modified graphite oxide) nanocomposite films were obtained by the solution intercalation technique as a possible drug delivery system. The heparin–benzalkonium chloride (BAC–HEP) was intercalated into graphite oxide (GO) layers to form GO–BAC–HEP (modified graphite oxide). Nanocomposite films were characterized by XRD, SEM, TEM, ATR-FTIR and TGA. The modified graphite oxide was observed to be homogeneously dispersed throughout the PDMS matrix. The effect of modified graphite oxide on the mechanical properties of the nanocomposite film was investigated. When the modified graphite oxide content was lower than 0.2 wt%, the nanocomposites showed excellent mechanical properties. Furthermore, nanocomposite films become delivery systems that release heparin slowly to make the nanocomposite films blood compatible. The in vitro studies included hemocompatibility testing for effects on platelet adhesion, platelet activation, plasma recalcification profiles, and hemolysis. Results from these studies showed that the anticoagulation properties of PDMS/GO–BCA–HEP nanocomposite films were greatly superior to those for no treated PDMS. Cell culture assay indicated that PDMS/GO–BCA–HEP nanocomposite films showed enhanced cell adhesion.
GO-COO-β-CD/CA inclusion (carboxylated graphene-β-cyclodextrin/chlorhexidine acetate) was fabricated with a graphene-based drug carrier. The reaction time and ratio of carrier to drug were optimized by X-ray diffraction spectra to ensure the complete wrapping of CA. Hemolysis test and recalcification test demonstrated that the inclusion possessed good blood compatibility due to the inherent biocompatibility of β-CD molecules in the carrier. The inclusion displayed excellent inhibition effect on both gram negative bacteria of Escherichia coli and gram positive bacteria of Staphylococcus Aureus, while showing no cytotoxicity. More importantly, the drug efficiency was greatly improved with CA dosage as less as one-third of the pure drug due to the synergistic effect of the drug and carrier. Dynamic simulation implies that the delivery profile of CA from the inclusion is in accordance with the first-order dynamic equation, i.e. ln(1-Mt/M) = −kt.
Chemotherapy is an effective method for treating cancer, clinically. However, side effects of drug and multidrug resistance restrict its application. In recent years, the combined treatment of chemotherapy and photothermal therapy (PTT) is becoming a promising method for treating cancer. PTT utilizes nanomaterials absorbing near-infrared light and producing heat to acquire advanced hyperthermia strategy for cancer treatment. Carbon nanomaterials with good biocompatibility, high surface area, and excellent photothermal properties are an excellent nanoplatform for drug delivery and PTT. Herein, porous carbon-coated magnetite nanoparticles (PCCMNs) were successfully synthesized by a one-pot solvothermal method. Magnetite, a contrast agent, can be used for magnetic resonance imaging. Hyaluronic acid was used to modify the PCCMNs to achieve targeted therapy. The obtained nanohybrid with a good photothermal effect can realize combined PTT/chemotherapy and will be a promising nanoplatform for high efficacy theranostics.
Abstract Oxidative stress and local overactive inflammation have been considered major obstacles in diabetic wound treatment. Although antiphlogistic tactics have been reported widely, they are also challenged by pathogen contamination and compromised angiogenesis. Herein, a versatile integrated nanoagent based on 2D reductive covalent organic frameworks coated with antibacterial immuno‐engineered exosome (PCOF@E‐Exo) is reported to achieve efficient and comprehensive combination therapy for diabetic wounds. The E‐Exo is collected from TNF‐α‐treated mesenchymal stem cells (MSCs) under hypoxia and encapsulated cationic antimicrobial carbon dots (CDs). This integrated nanoagent not only significantly scavenges reactive oxygen species and induces anti‐inflammatory M2 macrophage polarization, but also stabilizes hypoxia‐inducible factor‐1α (HIF‐1α). More importantly, the PCOF@E‐Exo exhibits intriguing bactericide capabilities toward Gram‐negative, Gram‐positive, and drug‐resistant bacteria, showing favorable intracellular bacterial destruction and biofilm permeation. In vivo results demonstrate that the synergetic impact of suppressing oxidative injury and tissue inflammation, promoting angiogenesis and eradicating bacterial infection, could significantly accelerate the infected diabetic fester wound healing with better therapeutic benefits than monotherapy or individual antibiotics. The proposed strategy can inspire further research to design more delicate platforms using the combination of immunotherapy with other therapeutic methods for more efficient ulcerated diabetic wounds treatments.
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