Wen Zhao

Fabrication of functional PLGA-based electrospun scaffolds and their applications in biomedical engineering

Electrospun PLGA-based scaffolds have been applied extensively in biomedical engineering, such as tissue engineering and drug delivery system. Due to lack of the recognition sites on cells, hydropholicity and single-function, the applications of PLGA fibrous scaffolds are limited. In order to tackle these issues, many works have been done to obtain functional PLGA-based scaffolds, including surface modifications, the fabrication of PLGA-based composite scaffolds and drug-loaded scaffolds. The functional PLGA-based scaffolds have significantly improved cell adhesion, attachment and proliferation. Moreover, the current study has summarized the applications of functional PLGA-based scaffolds in wound dressing, vascular and bone tissue engineering area as well as drug delivery system.

Preparation of animal polysaccharides nanofibers by electrospinning and their potential biomedical applications.

Animal polysaccharides belong to a class of biological macromolecules. They are natural biopolymers with numerous advantages for biomedical applications, such as biocompatibility, biodegradability, non-antigenicity and non-toxicity. Electrospinning is a versatile and facile technique which can produce continuous fibers with nanoscale from a wide range of natural and synthetic polymers. The review aims to provide an up-to-date overview of the preparation of animal polysaccharides nanofibers by electrospinning and their potential biomedical applications such as tissue engineering, wound healing, and drug delivery. Various animal polysaccharides including chitin and chitosan (CS), hyaluronic acid (HA), heparin and heparan sulfate (HS), and chondroitin sulfate (ChS), are discussed. The challenges and some useful strategies in electrospinning of animal polysaccharides also are summarized. In addition, future study of animal polysaccharides nanofibers by electrospinning is proposed.

Enhanced bactericidal potency of nanoliposomes by modification of the fusion activity between liposomes and bacterium

Background Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of Pseudomonas to conventional antibiotics made it imperative to develop new liposome formulations to overcome these mechanisms, and investigate the fusion between liposome and bacterium. Methods The rigidity, stability and charge properties of phospholipid vesicles were modified by varying the cholesterol, 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE), and negatively charged lipids 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol sodium salt (DMPG), 1,2-dimyristoyl-sn-glycero-3-phopho-L-serine sodium salt (DMPS), 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA), nature phosphatidylserine sodium salt from brain and nature phosphatidylinositol sodium salt from soybean concentrations in liposomes. Liposomal fusion with intact bacteria was monitored using a lipid-mixing assay. Results It was discovered that the fluid liposomes-bacterium fusion is not dependent on liposomal size and lamellarity. A similar degree of fusion was observed for liposomes with a particle size from 100 to 800 nm. The fluidity of liposomes is an essential pre-request for liposomes fusion with bacteria. Fusion was almost completely inhibited by incorporation of cholesterol into fluid liposomes. The increase in the amount of negative charges in fluid liposomes reduces fluid liposomes-bacteria fusion when tested without calcium cations due to electric repulsion, but addition of calcium cations brings the fusion level of fluid liposomes to similar or higher levels. Among the negative phospholipids examined, DMPA gave the highest degree of fusion, DMPS and DMPG had intermediate fusion levels, and PI resulted in the lowest degree of fusion. Furthermore, the fluid liposomal encapsulated tobramycin was prepared, and the bactericidal effect occurred more quickly when bacteria were cultured with liposomal encapsulated tobramycin. Conclusion The bactericidal potency of fluid liposomes is dramatically enhanced with respect to fusion ability when the fusogenic lipid, DOPE, is included. Regardless of changes in liposome composition, fluid liposomes-bacterium fusion is universally enhanced by calcium ions. The information obtained in this study will increase our understanding of fluid liposomal action mechanisms, and help in optimizing the new generation of fluid liposomal formulations for the treatment of pulmonary bacterial infections.

Preparation of amifostine polylactide-co-glycolide microspheres and its irradiation protective to mouse through oral administration

The objectives of this study were to prepare the amifostine polylactide-co-glycolide (PLGA) microsphere and investigate its irradiation protective to mouse through oral administration. Amifostine-loaded PLGA microsphere was formulated using a modified double emulsion-solvent evaporation technique. The microsphere particle was spherical with a mean diameter of 2.8u2009±u20090.1 µm. Release data of amifostine PLGA microsphere was tested in phosphate-buffered saline at 37°C using a dialysis method and its release profiles was biphasic, showing a relatively large burst effect (50%) over the first 6u2009h, followed by a slower release phase, which sustained with 80% amifostine released in 48u2009h and almost 100% release till 6 days (144u2009h). A diffusion-controlled release model (Higuchi equation, R2u2009=u20090.9725) was obtained for amifostine releasing from PLGA microsphere. The radiation experiment was performed by applied cobalt-60 γ-radiation source. One hour before γ-radiation exposure, the mouse was orally given free amifostine and PLGA microsphere, respectively. The irradiation effects, such as blood cell concentration, superoxidase dismutase (SOD) activity and malondialdehyde (MDA) level were monitored. The results indicated that amifostine PLGA microsphere was more irradiation protective to mouse than that of free amifostine under the same oral administration route.

Ethinylestradiol liposome preparation and its effects on ovariectomized rats’ osteoporosis

Ethinylestradiol liposome (EEL) was prepared by thin film evaporation–extrusion technique and its effects on ovariectomized rat osteoporosis were investigated. The liposomes were characterized with clear homogeneous lamellar vesicles and had the average size of 200u2009±u20091.5u2009nm. The long term stability of liposome formulations were tested over a 28-day period at 4°C and ethinylestradiol retention was approximately 80% up to 28 day. Release data of ethinylestradiol was tested in PBS pH 7.4 at 37°C using a dialysis method and its release profiles were biphasic, showing a relatively large burst effect over the first four hours, followed by a slower release phase. Ovariectomized rat model was used to investigate EEL effects on osteoporosis. After three months post-surgery, the rats were divided into two groups and injected intraperitoneally (IP) with 2 μg per kilogram per day of either free ethinylestradiol (EE) or encapsulated ethinlyestradiol (EEL). At termination of one month IP injection, the rats were killed and the bone mineral density (BMD) and alkaline phosphatase (ALP) were measured. BMD value in free EE group increased by 20.3 %, while it increased by 37.8 % in EEL group. According to ALP value, the two treatment groups increased by 28.6 % and 42.0 %, respectively. These data indicated that ethinlyetradiol liposome had better effect than that of free ethinylestradiol did in treatment of the ovariectomized rats’ osteoporosis. But the metabolites and biodistribution of ethinylestradiol liposome in vivo need to investigate in the further research work.

Enhanced Antimalarial Activity by a Novel Artemether-Lumefantrine Lipid Emulsion for Parenteral Administration

ABSTRACT Artemether and lumefantrine (also known as benflumetol) are difficult to formulate for parenteral administration because of their low aqueous solubility. Cremophor EL as an emulsion excipient has been shown to cause serious side effects. This study reports a method of preparation and the therapeutic efficacies of novel lipid emulsion (LE) delivery systems with artemether, lumefantrine, or artemether in combination with lumefantrine, for parenteral administration. Their physical and chemical stabilities were also evaluated. Furthermore, the in vivo antimalarial activities of the lipid emulsions developed were tested in Plasmodium berghei-infected mice. Artemether, lumefantrine, or artemether in combination with lumefantrine was encapsulated in an oil phase, and the in vivo performance was assessed by comparison with artesunate for injection. It was found that the lumefantrine lipid emulsion (LUM-LE) and artemether-lumefantrine lipid emulsion (ARM-LUM-LE-3) (1:6) began to decrease the parasitemia levels after only 3 days, and the parasitemia inhibition was 90% at doses of 0.32 and 0.27 mg/kg, respectively, with immediate antimalarial effects greater than those of the positive-control group and constant antimalarial effects over 30 days. LUM-LE and ARM-LUM-LE-3 demonstrated the best performance in terms of chemical and physical stabilities and antiplasmodial efficacy, with a mean particle size of 150 nm, and they have many favorable properties for parenteral administration, such as biocompatibility, physical stability, and ease of preparation.

Fusion between fluid liposomes and intact bacteria: study of driving parameters and in vitro bactericidal efficacy

Background Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of bacteria to conventional antibiotics made it imperative to develop new liposome formulations for antibiotics, and investigate the fusion between liposome and bacterium. Methods In this study, the factors involved in fluid liposome interaction with bacteria have been investigated. We also demonstrated a mechanism of fusion between liposomes (1,2-dipa lmitoyl-sn-glycero-3-phosphocholine [DPPC]/dimyristoylphosphatidylglycerol [DMPG] 9:1, mol/mol) in a fluid state, and intact bacterial cells, by lipid mixing assay. Results The observed fusion process is shown to be mainly dependent on several key factors. Perturbation of liposome fluidity by addition of cholesterol dramatically decreased the degree of fusion with P. aeruginosa from 44% to 5%. It was observed that fusion between fluid liposomes and bacteria and also the bactericidal activities were strongly dependent upon the properties of the bacteria themselves. The level of fusion detected when fluid liposomes were mixed with Escherichia coli (66%) or P. aeruginosa (44%) seems to be correlated to their outer membrane phosphatidylethanolamine (PE) phospholipids composition (91% and 71%, respectively). Divalent cations increased the degree of fusion in the sequence Fe2+ > Mg2+ > Ca2+ > Ba2+ whereas temperatures lower than the phase transition temperature of DPPC/DMPG (9:1) vesicles decreased their fusion capacity. Acidic as well as basic pHs conferred higher degrees of fusion (54% and 45%, respectively) when compared to neutral pH (35%). Conclusion Based on the results of this study, a possible mechanism involving cationic bridging between bacterial negatively charged lipopolysaccharide and fluid liposomes DMPG phospholipids was outlined. Furthermore, the fluid liposomal-encapsulated tobramycin was prepared, and the in vitro bactericidal effects were also investigated.

RP-HPLC ANALYSIS OF HYDROPHOBIC ALENDRONATE AMIDATED DERIVATIVES

The reversed phase high performance liquid chromatography (RP-HPLC) was evaluated for its application in the analysis of the quantiation of the alendronate derivatives. The anti-phase Agilent CLC-ODS C18 column was used at the temperature of 50°C. The RP-HPLC trace was monitored with a differential refractive index detector for the lack of ultraviolet (UV) absorbing groups in the derivative molecule. The mobile phase was an aqueous solution mixture of MeOH and H2O at pH 7.2, containing small amounts of dodecoulde tributyl bromide and disodium ethylente diamine tetraacetic acid. The chromatographic conditions, such as the concentration of ion-pairing agent, pH, and methanol content in mobile phase, were studied. This RP-HPLC method provides high separation and specificity to derivative analysis. In quantitative analysis, the method showed satisfactory precision (less than 0.62%) and recovery (higher than 98.3%), good linearity (r2 = 0.9994) with the linear range of 0.5 ∼ 250 μg·mL−1. The limit of quantification (0.5 μg·mL−1) and limit of detection (0.2 μg·mL−1) were also achieved.

Compatibility between Paclitaxel and Polymer Carrier

Several polymer-based drug delivery systems are being developed to enhance the extremely low water-solubility of paclitaxel (PTX). It is believed that there is a positive correlation between the compatibility of polymer-drug and the solubilization. In recent years, solubility parameters for polymer and drug were used to evaluate degree of compatibility between a drug and a polymer, which were measured using various experimental methods or estimated using the group contribution menthod (GCM). In this study, degree of compatibility between PTX and polymers were estimated by molar free energy of mixing (Δ̗mix) that was calculated through computer simulation. It is found that the degree of compatibility is: PTX-PTRP > PTX-PLBG > PTX-PLGA > PTX-PCL > PTX-PLA. It has been demonstrated that the result of this study is in accord with the Similar Dissolve Mutually Theory.

Fabrication and characterization of dual drug-loaded poly (lactic-co-glycolic acid) fiber-microsphere composite scaffolds

ABSTRACT The purpose of this work is to develop dual drug-loaded poly (lactic-co-glycolic acid) (PLGA) fiber-microsphere composite scaffolds with desired morphologies and dual drug loading properties, and to investigate the release kinetics of the dual drugs, both hydrophobic and hydrophilic, from the composite scaffolds. In this study, simvastatin (SIM) and bovine serum albumin (BSA) were used as model drugs, which were incorporated into the composite scaffolds by performing electrospinning and emulsion electrospraying simultaneously. The optimum condition for electrospraying (solution concentration: 0.06u2009g/mL; applied voltage: 15u2009kV; and flow rate: 0.6u2009mL/h) has been obtained to prepare PLGA microspheres. The release rate of SIM and BSA from the composite scaffolds fit the first order kinetics and the Higuchi model, respectively. The results indicated that fiber-microsphere composite scaffolds had the ability to load two types of drug, suggesting the scaffolds have great potential in the field of tissue engineering and combined therapies. GRAPHICAL ABSTRACT