Zhigao Wang

Preparation and rapid degradation of nontoxic biodegradable polyurethanes based on poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) and L-lysine diisocyanate

To obtain rapid biodegradable biomaterials, a biodegradable triblock oligomer poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) was designed and synthesized as a soft segment of polyurethane. Then new nontoxic biodegradable polyurethanes were prepared using the same stoichiometric ratio of PLA-PEG-PLA, L-lysine ethyl ester diisocyanate (LDI), and 1,4-butanediol (BDO). The molecular weights of polyurethanes were controlled by adjusting the polymerization temperature. The resulting polyurethanes were characterized by gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Furthermore, the biodegradability of the synthesized polyurethanes was evaluated at 37 °C in phosphate buffer solutions (PBS) under different pH values and enzymatic solution at pH 7.4. The results showed that these polyurethanes could be rapidly degraded in PBS and enzymatic solution, as demonstrated by weight loss measurements and scanning electron microscope (SEM) observations. The degradation rates of these polyurethanes were mainly regulated by microphase separation degree, and could be restrained in lower pH value PBS. Moreover, the degradation products did not significantly decrease the pH value of incubation media, which would be useful to improve biocompatibilities of these polyurethanes in vivo. The current work provides a more promising approach to prepare nontoxic biodegradable polyurethanes with rapid degradation rates. These new materials may find potential use for drug delivery systems and magnetic resonance imaging (MRI) contrast agents.

Cellular uptake of polyurethane nanocarriers mediated by gemini quaternary ammonium.

The effective passage of drug formulations into tumor cells is a key factor in the development of nanoscale delivery systems. However, rapid cellular uptake with reduced toxicity remains a great challenge for efficient and safe delivery. In this study, we first use gemini quaternary ammonium (GQA) as a cell internalization promoter to enhance the cellular uptake of drug nanocarriers. It is found that a twenty times faster cell internalization could be achieved by introducing GQA into biodegradable multiblock polyurethane nanomicelles, as confirmed by flow cytometry and confocal laser scanning microscopy (CLSM) studies. Meanwhile, an added methoxyl-poly(ethylene glycol) (mPEG) outer corona could protect these cationic micelles from cytotoxicity at high concentrations, as verified by methyl tetrazolium (MTT) assay. Moreover, GQA not only acts as an enhancer for rapid cellular entry, but also plays an important role in controlled self-assembly and high drug loading capacity. Our work offers a new understanding on the role of cationic surfactants; and provides a facile and economical approach for the design of versatile drug nanocarriers to achieve efficient delivery and good biocompatibility.

Fabrication and characterization of waterborne biodegradable polyurethanes 3-dimensional porous scaffolds for vascular tissue engineering.

In this study, a series of 3-D interconnected porous scaffolds with various pore diameters and porosities was fabricated by freeze-drying with non-toxic biodegradable waterborne polyurethane (WBPU) emulsions of different concentration. The structures of these porous scaffolds were characterized by scanning electron microscopy (SEM), and the pore diameters were calculated using CIAS 3.0 software. The pores obtained were 3-D interconnected in the scaffolds. The scaffolds obtained at different pre-freeze temperatures showed a pore diameter ranging from 2.8 to 99.9 μm with a pre-freezing temperature of −60°C and from 13.1 to 229.1 μm with a pre-freezing temperature of −25°C. The scaffolds fabricated with WBPU emulsions of different concentration at the same pre-freezing temperature (−25°C) had pores with mean pore diameter between 90.8 and 39.6 μm and porosity between 92.0 and 80.0%, depending on the emulsion concentration. The effect of porous structure of the scaffolds on adhesion and proliferation of human umbilical vein endothelial cells (HUVECs) cultured in vitro was evaluated using the MTT assay and environmental scanning electron microscopy (ESEM). It was found that the better adhesion and proliferation of HUVECs on 3-D scaffolds of WBPU with relative smaller pore diameter and lower porosity than those on scaffolds with larger pore and higher porosity and film. Our work suggests that fabricating a scaffold with controllable pore diameter and porosity could be a good method to be used in tissue-engineering applications to obtain carriers for cell culture in vitro.

Simulation of self-assembly behaviour of fluorinated phospholipid molecules in aqueous solution by dissipative particle dynamics method

In order to prepare novel biomaterials, it is essential to investigate the self-assembly behaviour of molecules containing both hydrophobic and hydrophilic groups, and to understand their structural change and morphological development. In this paper, we studied the self-assembly behaviour of fluorinated double-chain phospholipid molecules in aqueous solution at various simulation steps, concentrations, temperatures and pH values via the dissipative particle dynamics simulation method. The self-assembly behaviours of hydrogenated analogues and fluorinated single-chain phospholipids at various concentrations were also investigated for comparison. It was found that all molecules could form microsphere at low concentration, and aggregated to form various shapes with the increase of concentration. Fluorinated double-chain phospholipids were apt to form bilayer membrane more easily than hydrogenated/fluorinated single-chain phospholipids. Besides concentration, temperature and pH value of the aqueous solution also influence the self-assembly behaviour of the investigated molecules. A stable bilayer membrane could be achieved for the fluorinated double-chain phospholipids at a relatively high concentration when pH value and temperature of aqueous solution were close to physiological conditions, i.e., pH 7 and T = 37°C. This work provides a direct ‘observation’ of self-assembly behaviour in the molecular level, which is important for the development of novel biomaterials, where surface structure is required to be well controlled.

Synthesis and self-assembly of an amino-functionalized hybrid hydrocarbon/fluorocarbon double-chain phospholipid.

In this article, we designed and synthesized an amino-functionalized hybrid hydrocarbon/fluorocarbon double-chain phospholipid (ACFPC) containing one chain with the hydrophobic fluorocarbon chain and terminal amino, amide, and ether linkages and one chain with the hydrocarbon chain. The novel reactive phospholipid was fully characterized with Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), and mass spectrometry (MS). Then the self-assembly behaviors of the hybrid double-chain phospholipid in aqueous and acidic media were investigated with transmission electron microscopy (TEM), the critical micelle concentration (cmc), dynamic light scattering (DLS), and the hydrocarbon double-chain phospholipid (ACCPC) for comparison. Moreover, their self-assembled structures in aqueous and acidic media were simulated using the dissipative particle dynamics (DPD) method. These results suggest that the fluorocarbon/hydrocarbon hybrid-chain phospholipid can self-assemble into a more stable microstructure compared to the double hydrocarbon chain phospholipid, which will have the potential ability to self-assemble into a more stable minicking biomembrane structure onto material surfaces to inhibit protein adsorption under complicated physiological conditions.