紫杉醇聚合物纳米囊泡的制备和体外释放研究

Objective To develop paclitaxol (PTX)-loaded polymersomes based on poly (ε-caprolactone)-block-poly (ethylene glycol)-block-poly (ε-caprolactone)(PCL-b-PEG-b-PCL, PCEP) amphiphilic triblock copolymers. Methods A series of PCEP copolymers was synthesized by ring-opening polymerization of ε-caprolactone initiated by PEG. The block copolymers were characterized by FT-IR、1H NMR and GPC. PTX-loaded polymersomes were prepared by thin-film and ultrasonic dispersion method and characterized in terms of morphology,particle size and size distribution, encapsulation efficiency and in vitro release. The effect of different hydrophilic and hydrophobic chain length on the drug-loading content, entrapment efficiency, size and size distribution and in vitro release were also investigated. Results The PTX-loaded polymersomes showed nanometer size and spherical morphology with core and shell. The sizes of PTX-loaded polymersomes increased with the increasing of the molecular weight of PCEP. The PTX-loaded polymersomes showed a continuous and steady release of PTX without initial burst release. The release rate increased with the increasing of hydrophilic PEG chain content and decreased with the increasing of hydrophobic PCL chain content. Conclusion For the first time, a novel PTX-loaded polymersomes was developed based on PCL-b-PEG-b-PCL amphiphilic triblock copolymers. The PTX-loaded polymersomes showed nanometer size, narrow size distribution and high drug encapsulation efficiency.These results indicate that PTX-loaded polymersomes could be a promising novel controlled release dosage form to increase therapeutic effect with decreased toxic and side effect of PTX.     

Preparation and Evaluation in Vitro of BCNU-Loaded PLA Nanoparticles

In this study, using a spontaneous emulsification/solvent extraction method, BCNU-Ioaded PLA nanoparticles (NPs) with small particle size and narrow size distribution have been acquired. The particle size of the NPs ranged from 40-60 nm and 100-200 nm according to different requirements. SEM and TEM showed that the particle size considerably decreases with increasing emulsification concentration and decreasing PLA concentration and ratio of oil to water. The highest drug loading ratio and drug encapsulation efficiency of NPs were 5. 63% and 33.45%. The results demonstrated that decrease of initial BCNU content resuited in a noticeably increased encapsulation yield. A thorough study in vitro showed that the drug could be steadily released from NPs for one week. In addition, drug-loaded NPs had higher antitumor activity, compared with free BCNU,and sustained drug release characteristics as well.     

小粒径磁共振成像超敏感纳米对比剂的研制及初步动物实验

Objective To synthesize a small size and super-sensitive magnetic resonance imaging (MRI) nano-contrast agent for preliminary animal experiment and to explore the feasibility for its use in molecular imaging studies.Methods Polyethylene glycol (PEC) was used for ring-opening polymerization of ε-caprolactone(CL), and amphiphilic PEG-b-PCL block polymer was prepared by self-assembly technique.Single particle superparamagnetic iron oxide (SPIO) was loaded at the hydrophobic core of PEG-b-PCL to develop a nano-contrast agent.The particle diameter and SPIO-loading density were respectively determined by transmission electron microscope and atomic absorption spectroscopy.Echo multiplanar sequence was used for T2 value test, with transverse relaxation rate R2 computed.Meanwhile, magnetic properties were tested.After intravenous injection via caudal vein of Balb/c nude mice, the distributions and circulation time of this nano- particle were analyzed using MRI scanner at before injection and lh, 3h, 6 h, 12 h and 24 h after injection.Results The micelle diameter was around (38+3) nm and the content of Fe3O4 (wt%) was 37.0%.The transverse relaxation rate R2 was 110 Fe(mmol/L)-1 ·s-1.Superparamagnetism was observed in magnetic property test.After intravenous injection, the nano-particles were mainly distributed in the liver with a long circulation time.Signal intensity at 1 h decreased significantly when compared with that of before injection (120±32 vs 4986±0, P＜0.05) , and then decreased to (88±28) at 24 h (P＜0.05).Conclusion The nanometer micelle loaded with single SPIO particle demonstrates its potential as a powerful MRI contrast agent for molecular imaging studies because of its small size and high sensitivity.     

States of Water in Hydrogels Containing with Glyceryl Methacrylate

Hydrogel materials were prepared by thermopolymerization with different content of glyceryl methacrylate and hydroxyethyl methacrylate. The different states of water in swelling hydrogels were described and studied by differential scanning calorimetry （DSC）. It was found that the hydrophilicity of GMA was stronger than HEMA, the water content and bound water of GMA hydrogel are higher than HEMA hydrogel. With the increase of GMA content, the content of free water in hydrogel increased. When GMA content was lower than 50%, the increase of GMA content also increased the content of bound water; but when GMA content was higher than 50%, the increase of GMA content decreased the content of bound water, which was caused by the chain hydrogen bond formed on the GMA chain with hydroxyl group each other.     

Optimization of preparation method of atorvastatin calcium sustained-release microspheres北大核心

BACKGROUND: In recent years, studies have found that statins have significant effects on regulating bone metabolism, repairing bone microstructure, inhibiting inflammation, promoting cell proliferation, repairing vascular endothelium, and regulating signal pathway conduction. OBJECTIVE: To optimize the preparation parameters of atorvastatin calcium sustained-release microspheres, to prepare sustained-release microspheres with large drug loading and regular morphology. METHODS: The bovine serum albumin sustained-release microspheres loaded with atorvastatin calcium were prepared by desolvent method. The main factors affected the preparation of the microspheres were screened out. The four key related factors were bovine serum albumin concentration (40, 70, 100 g/L), pH value (7, 8, 9), dosage of atorvastatin calcium (200, 300, 400 µg), and ethanol addition rate (0.2, 0.5, 1 mL/min). The optimal preparation conditions of large drug loading were screened by orthogonal test. Atorvastatin calcium-loaded bovine serum albumin sustained-release microspheres were prepared under optimal parameters and placed in PBS for sustained-release performance testing. RESULTS AND CONCLUSION: (1) The optimum preparation parameters were as follows. The concentration of bovine serum albumin was 100 g/L; the pH value was 7; the dosage of atorvastatin calcium was 400 µg; the addition rate of ethanol was 0.2 mL/min. (2) The microspheres prepared under this parameter had regular morphology and smooth surface. The particle size was (425.0±13.8) nm and the encapsulation efficiency of drug loaded microspheres was up to 85.70%. The in vitro release time could last for more than 48 hours, and the cumulative release reached 73% which had a relatively good sustained release effect. (3) It is indicated that the stable sustained-release microspheres loaded with atorvastatin calcium were successfully prepared. The sustained-release microspheres with high drug loading and stability can achieve sustained drug release. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Preparation and in vitro evaluation of vancomycin hydrochloride@polylactic acid-glycolic acid copolymer-chitosan-hyaluronic acid composite sustained-release microspheres北大核心

BACKGROUND: Local antibiotic slow-release system can solve the problems of total toxicity caused by systemic antibiotics and short half-life of short-term local antibiotics. OBJECTIVE: To prepare polylactic acid-glycolic acid copolymer-chitosan-hyaluronic acid composite sustained-release microspheres loaded with vancomycin and evaluate its performance. METHODS: Vancomycin-loaded polylactic acid-glycolic acid copolymer-chitosan-hyaluronic acid composite sustained-release microspheres and unloaded polylactic acid-glycolic acid copolymer-chitosan-hyaluronic acid composite microspheres were prepared by emulsion method. Mass concentrations of vancomycin in the drug-loaded microspheres were 25, 50, and 100 g/L. The drug-loading amount, encapsulation efficiency, and in vitro sustained release properties of the drug-loaded microspheres were detected. The three kinds of drug-loaded microspheres were co-cultured with Staphylococcus aureus bacteria separately, and the antibacterial rate was detected within the corresponding time points. The four kinds of microsphere extracts were co-cultured with MC3T3-E1 cells and MG-63 cells, and the cytotoxicity was detected by CCK-8 method after 1, 3, and 7 days of culture. RESULTS AND CONCLUSION: (1) The encapsulation efficiencies of 25, 50, and 100 g/L drug-loaded microspheres were (79.70±5.11)%, (86.41±3.91)%, and (63.18±1.96)%, and the drug loading was (3.98±0.26)%, (8.64±0.39)%, and (12.63±0.39)%. The encapsulation efficiency of 50 g/L drug-loaded microspheres was higher than that of 100 g/L drug-loaded microspheres (P < 0.05). The drug loading of 100 g/L drug-loaded microspheres was higher than that of the other two groups (P < 0.05). (2) Three kinds of drug-loaded microspheres had no obvious burst release within 24 hours, of which the drug release rate of 50 g/L drug-loaded microspheres at different time points was faster than that of the other two groups. The drug release amount of 100 g/L drug-loaded microspheres at different time points was higher than that of the other two groups, and the drug mass concentration of the three groups was higher than minimum antibacterial concentration of vancomycin at 56 days. (3) All three kinds of drug-loaded microspheres could effectively kill Staphylococcus aureus within a certain period of time. From 14 to 28 days, the relative colony rate of the three kinds of microspheres was lower than 3%, indicating that three kinds of drug-loaded microspheres can continuously and effectively kill Staphylococcus aureus. (4) The 25 and 50 g/L drug-loaded microspheres have no obvious cytotoxicity to MC3T3-E1 cells and MG-63 cells, and 100 g/L drug-loaded microspheres have certain cytotoxicity. (5) The results show that the VA@PLGA-CS-HA microspheres have good sustained-release performance, antibacterial ability and biological tissue compatibility. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

聚乙烯亚胺-聚乙二醇-siRNA纳米复合物的制备和理化性质的研究

Objective To investigate the preparation method and characteristics of polyethyleneimine- polyethylene glycal (PEI- PEG) siRNA nanocomplex to improve the cell transfection efficiency of siRNA. Methods PEI-PEG copolymer was synthesized as gene carrier and complexed with siRNA targeting to CD44v6 to form PEI-PEG-siRNA nanoparticle. The size and zeta potential was measured. The morphology of the complex was observed by scanning electron microscopy. The complex abilities of the nanocomplex were validated by gel retardation assay. And the transfection efficiency of nanocomplexes at different N/P ratios was measured by flow cytometry. Results The nanoparticles appeared spherical,uniform in size, and well-dispersed. When N/P ratio was over 10, the size of nanocomplex decreased as N/P value increased. Meanwhile, the zeta potential was positive and increased. At this time, siRNA was completely complexed with PEI-PEG, producing a fluorescence quenching phenomenon. The flow cytometry showed that the transfection efficiency of nanocomplexes was improved as N/P value increasied. When N/P was 30, the transfection efficiency was (75.6±9.2)%. Conclusion PEI-PEG may be a promised gene carrier and can provide evidences for related research of PEI-PEG-siRNA nanoparticles in animals and in vitro experiments.     

Preparation of Chitosan/Poly(L-Lactide) Porous Composite Scaffolds

This research investigates the formation of chitosan/poly(L-lactide) (CS/PLLA) porous composite scaffold using a novel emulsion freeze-drying technique. First, an oil in-water (O/W) emulsification system was used in the presence of surfactant Tween-80, in which CS solution was used as the water phase and PLLA solution was used as the oil phase. The emulsion was observed by inverted microscope (×200). The emulsion droplet was spherical and uniform in size. FT-IR analysis revealed that there were hydrogen bonding interactions between CS and PLLA components. The microstructure and physical properties of the scaffolds were also analyzed. The SEM results showed that composite scaffolds formed well interconnected pore structure and homogenous distribution of CS and PLLA. When the content of PLLA reached 50%, the porosity of CS/PLLA composite scaffolds were between 83%-91% and density in the range of 0.047 to 0.11 g/cm3. The porosity showed a slight decrease and the density increased with the increase of PLLA dose. The compressive strength increased from 0.32 to 0.43 MPa, while the compressive modulus increased from 1.99 to 3.91 MPa as the PLLA contents increased from 10% to 50%.     

Favre-Racouchot syndrome associated with eyelid papilloma:a case report

A 55-year-old Chinese man presented with an asymptomatic pedunculated elevation on his left lower eyelid which had been gradually increasing in size during the past three years.The patient was diagnosed with eyelid papilloma by pathological examination.Concomitantly,the patient developed open comedones with a bilateral linear distribution,along with oblique wrinkle lines in his infraorbital regions.These lesions were noninflammatory and remained unchanged for two years.To the best of our knowledge,this distribution of open comedones,especially in combination with eyelid papilloma,has not been reported previously in Favre-Racouchot syndrome.     

Induction of Thl-Type Immune Response by Chitosan Nanoparticles Containing Plasmid DNA Encoding House Dust Mite Allergen Der p 2 for Oral Vaccination in Mice

This study was to prepare the chitosan-pDer p 2 nanoparticles and to investigate the effect of chitosan-DNA nanoparticles on immune response in mice by oral delivery of chitosan-DNA nanoparticles. The nanoparticles were synthesized by complexing chitosan with plasmid DNA. The DNA was fully complexed into chitosan-DNA nanoparticles, suggesting a 100% encapsulation efficiency. Chitosan-DNA complex renders a significant protection of the plasmid. No effect on cell viability was observed in both cell types and average cell viability over 100% was obtained. Oral gene delivery with chitosan-DNA nanoparticles can generate a higher level expression of gene in vivo. Oral chitosan-pDer p 2 nanoparticles in BALB/c mice can induce IFN-γ in serum and prevent subsequent sensitization of Th2 cell-regulated specific IgE responses. The data indicate that the oral administration of chitosan-pDer p 2 nanoparticles results in the expression of Der p 2 in the epithelial cells of both stomach and small intestine and the induction of Th1-type immune response. Cellular ＆ Molecular Immunology.