Shuo Fang

Bienzymatically crosslinked gelatin/hyaluronic acid interpenetrating network hydrogels: preparation and characterization

Hydrogels that mimic the extracellular matrix in both composition and crosslinking chemistry have great potential in the development of tissue engineering scaffolds. Natural polymer hydrogels crosslinked by enzymes have excellent biocompatibility due to their natural origin and the mild reaction conditions, but usually suffer from a lack of mechanical strength. In order to improve the mechanical properties, hydrogels of gelatin/hyaluronic acid with interpenetrating network (IPN) structure were prepared by dual enzymatic crosslinking, using transglutaminase (mTG) to crosslink gelatin, and horseradish peroxidase (HRP) to crosslink hyaluronic acid (HA) grafted with tyramine (HA-Ty), respectively. The gelation processes of the gelatin/HA IPN hydrogels were monitored by rheometer. The data confirmed the formation of dual networks: one gelatin network crosslinked by mTG and the other HA network crosslinked by HRP. Hereafter, the results of mechanical test showed the compressive strength of the gelatin/HA-Ty IPN hydrogels was 10 folds higher than that of pure HA hydrogels. Furthermore, the in vitro enzymatic degradation, equilibrium water content, cytotoxicity and cell adhesion of the IPN hydrogels were evaluated in detail. The preliminary biological evaluation revealed the hydrogels could support cell adhesion and proliferation. Summary, the gelatin/HA IPN hydrogels prepared by bienzymatic crosslinking method possess excellent biocompatibility and mechanical properties, which are expected to be novel biomaterials in the field of tissue engineering and in situ wound repair.

Liposomes Assembled from a Dual Drug-tailed Phospholipid for Cancer Therapy

We report a novel dual drug-tailed phospholipid which can form liposomes as a combination of prodrug and drug carrier. An amphiphilic dual chlorambucil-tailed phospholipid (DCTP) was synthesized by a straightforward esterification. With two chlorambucil molecules as hydrophobic tails and one glycerophosphatidylcholine molecule as a hydrophilic head, the DCTP, a phospholipid prodrug, undergoes assembly to form a liposome without any additives by the thin lipid film technique. The DCTP liposomes, as an effective carrier of chlorambucil, exhibited a very high loading capacity and excellent stability. The liposomes had higher cytotoxic effects to cancer cell lines than free DCTP and chlorambucil. The in vivo antitumor activity assessment indicated that the DCTP liposomes could inhibit the tumor growth effectively. This novel strategy of dual drug-tailed phospholipid liposomes may be also applicable to other hydrophobic anticancer drugs which have great potential in cancer therapy.

Functional vesicles formed by anticancer drug assembly

In this Letter, a new type of nitrogen mustard conjugate vesicles is developed to improve the stability and efficiency of anticancer drug. Benzoic acid nitrogen mustard-peptide (AAAK) conjugate was designed and synthesized, which was found to self-assemble into vesicles in water. The formation of the vesicles was confirmed by dynamic light scattering (DLS), transmission electron microscopy (TEM) and circular dichroism (CD). The degradation data revealed that the benzoic acid nitrogen mustard peptide (AAAK) conjugate vesicles are more stable than the parent drug in aqueous solution. Furthermore, MTT assay revealed that the free drug conjugate has similar antitumor activity against MCF-7, Hela, HepG-2 cell lines compared with the parent drug. The benzoic acid nitrogen mustard-peptide conjugate vesicles may have potential in the treatment of cancers.

Liposome-like nanocapsules of dual drug-tailed betaine for cancer therapy

A novel dual drug-tailed betaine conjugate amphiphile has been firstly synthesized in which the polar headgroup is derived from glycine betaine and the hydrophobic tails are chlorambucil molecules. The newly prepared conjugate undergoes self-assembly to form stable liposome-like nanocapsules as an effective carrier with high drug loading capacity. The nanocapsules showed higher cytotoxic effects to cancer cell lines than those of free chlorambucil in vitro, and inhibited tumor growth effectively in vivo. This strategy that utilizes new dual drug-tailed betaine conjugate amphiphile to construct a self-assembled nanoparticle drug delivery system may have great potential in cancer chemotherapy.

Dimeric camptothecin derived phospholipid assembled liposomes with high drug loading for cancer therapy

In this study, a newly liposomal formulation of camptothecin (CPT) based on the dimeric camptothecin glycerophosphorylcholine (di-CPT-GPC) prodrug was developed. The di-CPT-GPC prodrug was synthesized through the heterogeneous conjugation of camptothecin-20 succinate with glycerophosphorylcholine. It undergoes assembly to form liposomes without any excipient through the thin film hydration method, which, confirmed by dynamic light scattering (DLS), have an average diameter of approximately 165 ± 5 nm. Observations on cryogenic transmission electron microscopy (cryo-TEM) demonstrated that the liposomes possess a typical multilamellar vesicle structure with a bilayer thickness of approximately 4 nm. The liposomes with a CPT loading up to 62 wt% maintained good stability in simulated physiological fluid. This can be attributed to the protection of the liposomes having CPT groups sequestered within the bilayer interior. Moreover, the in vitro release behavior of di-CPT-GPC liposomes was monitored using different media. The results showed that the liposomes could dissociate and sustainably release free active form CPT in a weak acidic environment. In vitro anticancer activity tests indicated that di-CPT-GPC liposomes had comparable cytotoxicity to the parent drug against MCF-7, HeLa and HepG-2 cells. Finally, a preliminary in vivo antitumor evaluation revealed that the liposomes inhibited tumor growth. Taken together, the di-CPT-GPC assembled liposomes with high drug loading could be a promising nanoformulation of CPT.

A novel consequent-pole hybrid excited vernier permanent-magnet machine for EV/HEV applications

Vernier Permanent-magnet machine (VPMM) has been recognized in recent years as a substitute for permanent magnet synchronous machines (PMSM) in direct-drive applications such as wind turbine generators, motorcycles and electric vehicle/hybrid electric vehicle (EV/HEV) [1].

Thermal analysis of consequent-pole hybrid vernier permanent-magnet machine for EV/HEV applications

Since vernier permanent-magnet machine (VPMM) has the merit of low-speed operation with high output torque due to the “magnetic-gearing” effect [1], they have been used in the direct-drive applications such as wind power generator, electric vehicle/hybrid electric vehicle (EV/HEV) [2,3].

Modular dual three-phase fractional-slot overlapping windings for reducing rotor losses of permanent magnet synchronous machines

Due to high torque density, low torque ripple, high efficiency, excellent fault-tolerance capability and convenient manufacturing, fraction-slot concentrated windings (FSCWs) are desirable to be used in high performance permanent magnet (PM) synchronous machines.

Torque characteristics of dual stator permanent magnet vernier machine with different pole/slot combinations

Traditional direct-drive permanent magnet synchronous machine (PMSM) suffers from large bulk and complex topology structure, which extremely limits its industrial applications. As a novel embranchment of PMSM, PM vernier machine (PMVM) incorporates the magnetic gear effects into conventional PMSM producing high torque at a relatively low speed, which is desirable for direct-drive applications. Recently, the specific magnetic field modulation effect and high output torque ability have been subtly incorporated into PMVM, which simultaneously enables the sinusoidal back-EMF waveform, high power density, efficient thermal dissipation. However, the torque characteristics of PMVMs with different pole-slot combinations and gear ratios have not been studied systemically as yet. In this paper, two representative dual stator PMVMs are designed to analyze the torque characteristics in detail with particular emphasis on the dominant influence of pole-slot combinations. In addition, gear ratio selecting is also investigated through the analysis of the electromagnetic characteristics of the designed PMVMs, which provides further unique insights into the design and optimization of PMVMs.