Phosphorylcholine/Heparin Composite Coatings on Artificial Lung Membrane for Enhanced Hemo-compatibility.

As the key component of extracorporeal membrane oxygenation (ECMO), artificial lung membranes have low gas permeability and plasma leakage problems, and the contact between membrane materials and blood can cause coagulation, leading to the blockage of medical equipment and seriously threatening the safety of human life. In our work, poly(4-methyl-1-pentene) hollow fiber membranes (PMP HFMs) were prepared by the thermally induced phase separation (TIPS) method, the redox method was adopted for the surface hydroxylation of PMP HFMs, and then, heparin (Hep) and 2-(methacryloyloxy)ethyl(2-(trimethylammonio)ethyl) phosphate (MPC) were grafted to the surface of PMP HFMs to prepare anticoagulant coatings. The gas permeability and hemo-compatibility of the coatings were investigated by various characterization methods, such as gas flow meter, scanning electron microscope, extracorporeal circulation experiment, etc. The results show that PMP HFMs possess a bicontinuous pore structure with a dense surface layer, which could maintain good gas permeability with an oxygen permeance of 0.8 mL/bar·cm2·min and stable gas selectivity. Furthermore, the whole blood circulation of rabbit indicated that a composite surface of bioactive Hep and biopassive MPC might be used as artificial lung membranes without the formation of thrombosis within 21 days.

Supramolecular Polymerization-Induced Nanoassemblies for Self-Augmented Cascade Chemotherapy and Chemodynamic Therapy of Tumor.

The clinical application of chemodynamic therapy is impeded by the insufficient intracellular H2 O2 level in tumor tissues. Herein, we developed a supramolecular nanoparticle via a simple one-step supramolecular polymerization-induced self-assembly process using platinum (IV) complex-modified ß-cyclodextrin-ferrocene conjugates as supramolecular monomers. The supramolecular nanoparticles could dissociate rapidly upon exposure to endogenous H2 O2 in the tumor and release hydroxyl radicals as well as platinum (IV) prodrugs in situ, which is reduced into cisplatin to significantly promote the generation of H2 O2 in the tumor tissue. Thus, the supramolecular nanomedicine overcomes the limitation of conventional chemodynamic therapy via the self-augmented cascade radical generation and drug release. In addition, dissociated supramolecular nanoparticles could be readily excreted from the body via renal clearance to effectively avoid systemic toxicity and ensure long term biocompatibility of the nanomedicine. This work may provide new insights on the design and development of novel supramolecular nanoassemblies for cascade chemo/chemodynamic therapy.

Preparation, function, and safety evaluation of a novel degradable dermal filler, the cross-linked poly-γ-glutamic acid hydrogel particles.

Poly-γ-glutamic acid (PGA) is a naturally degradable hydrophilic linear microbial polymer with moisturizing, immunogenic, cross-linking, and hydrogel water absorption properties similar to hyaluronic acid, a biomaterial that is commonly used as a dermal filler. To explore the development feasibility of cross-linked PGA as a novel dermal filler, we studied the local skin response to PGA fillers and the effect of various cross-linking preparations on the average longevity of dermal injection. Injection site inflammation and the formation of collagen and elastin were also determined. PGA hydrogel particles prepared using 28% PGA and 10% 1,4-butanediol diglycidyl ether showed optimal filler properties, resistance to moist heat sterilization, and an average filling longevity of 94.7 ± 61.6 days in the dermis of rabbit ears. Local redness and swelling due to filler injection recovered within 14.2 ± 3.6 days. Local tissue necrosis or systemic allergic reactions were not observed, and local collagen formation was promoted. Preliminary results suggested that dermal injection of cross-linked PGA particles appeared safe and effective, suggesting that cross-linked PGA particles could be developed as a new hydrogel dermal filler.

A systematic evaluation of the biocompatibility of cucurbit[7]uril in mice.

As one of the most water-soluble members in the macrocyclic cucurbit[n]uril (CB[n]) family, CB[7] has attracted increasing attention in pharmaceutical and biomedical fields. Despite extensive studies regarding the potential use of CB[7] for biomedical applications, its full safety and toxicity profile in a clinically relevant model is still lacking. Herein we report the full biocompatibility profile of CB[7], administered orally, peritoneally or intravenously in mice, respectively. Body-weight changes showed no significant differences among various groups of mice after they were administered with CB[7] at a single dose of 5 g/kg orally, 500 mg/kg peritoneally and 150 mg/kg intravenously, respectively. Hematology tests, as well as hepatic and renal function biochemical markers tests, of the blood collected from these mice sacrificed 21 days after CB[7] administration all exhibited normal ranges of values that were comparable with those of the control group. Moreover, histopathological analysis on the sections of major organs (including the heart, liver, spleen, lungs and kidneys) and gastrointestinal tissues revealed no detectable injuries and inflammatory cells infiltration. Taken together, these results suggest an excellent biocompatibility profile of CB[7] in mice, which provide important foundations for further investigations and even clinical applications of CB[7] in biomedical areas.

Polymeric Nanomedicine with "Lego" Surface Allowing Modular Functionalization and Drug Encapsulation.

Surface functionalization of nanoparticles (NPs) is of pivotal importance in nanomedicine. However, current strategies often require covalent conjugation that involves laborious design and synthesis. Herein, cucurbit[7]uril (CB[7])-decorated poly(lactic acid) (PLA)/poly(lactic-co-glycolic acid) (PLGA) NPs are developed and exploited for the first time as a novel, biocompatible, and versatile drug delivery platform with a noncovalently tailorable surface. CB[7] on the surface of NPs, acting as a "Lego" base block, allowed facile, modular surface modification with a variety of functional moieties or tags that are linked with amantadine (a complementary "Lego" piece to the base block), including amantadine-conjugated folate, polyethylene glycol, and fluorescein isothiocyanate. In addition, surface CB[7] also provided an opportunity for encapsulation of a secondary drug, such as oxaliplatin, into the cavity of the base block CB[7], in addition to a primary drug (e.g., paclitaxel) loaded into PLA/PLGA NPs, for a possible synergistic chemotherapy. This proof of concept not only provides the first versatile PLA/PLGA nanomedicine platform with "Lego" surface for modular functionalization and improved drug delivery but also offers new insights into the design and development of novel nanomedicine with a modular surface.

Facile Assembly of Cost-Effective and Locally Applicable or Injectable Nanohemostats for Hemorrhage Control.

Currently, there is still unmet demand for effective and safe hemostats to control abnormal bleeding in different conditions. With the aim to develop affordable, safe, effective, easily stored, and low-cost hemostats, we developed a series of positively charged nanoparticles by a facile one-pot assembly approach. In this strategy, nanoparticles were formed by cholic-acid-mediated self-assembly of polyethylenimine (PEI). Regardless of different structures of cholic acids and PEIs, well-defined nanoparticles could be successfully formed. The assembly process was dominated by multiple interactions between cholic acid and PEI, including electrostatic, hydrogen bonding, and hydrophobic forces. In vitro studies showed that assembled nanoparticles effectively induced aggregation and activation of platelets. Local application of aqueous solution containing nanoparticles assembled by different cholic acids and PEIs significantly reduced bleeding times in different rodent models including tail transection in mice as well as liver bleeding and femoral artery bleeding in rats or rabbits. Moreover, intravenous (i.v.) injection of this type of positively charged nanoparticles notably prevented bleeding in the femoral artery in rats by targeting the injured site via opsonization of nanoparticles with fibrinogen. By contrast, a control negatively charged nanoparticle showed no hemostatic activity after i.v. delivery. Also, preliminary evaluations in rats revealed a good safety profile after i.v. administration of assembled nanoparticles at a dose 4-fold higher than that used for hemostasis. These results demonstrated that cholic acid/PEI-assembled positive nanoparticles may function as cost-effective and locally applicable or injectable nanohemostats for hemorrhage control in the civilian setting and on the battlefield.

Biocompatible reactive oxygen species (ROS)-responsive nanoparticles as superior drug delivery vehicles.

A novel reactive oxygen species (ROS)-responsive nanoplatform can be successfully manufactured from a ROS-triggerable ß-cyclodextrin material. Extensive in vitro and in vivo studies validate that this nanoscaled system may serve as a new drug delivery vehicle with well-defined ROS-sensitivity and superior biocompatibility. This nanocarrier can be used for ROS-triggered transport of diverse therapeutics and imaging agents.