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This study aimed to explore the link between block copolymers' interfacial properties and nanoscale carrier formation and found out the influence of length ratio on these characters to optimize drug delivery system. A library of diblock copolymers of PEG-PCL and triblock copolymers with additional PEI (PEG-PCL-PEI) were synthesized. Subsequently, a systematic isothermal investigation was performed to explore molecular arrangements of copolymers at air/water interface. Then, structural properties and drug encapsulation in self-assembly were investigated with DLS, SLS and TEM. We found the additional hydrogen bond in the PEG-PCL-PEI contributes to film stability upon the hydrophobic interaction compared with PEG-PCL. PEG-PCL-PEI assemble into smaller micelle-like (such as PEG-PCL4006-PEI) or particle-like structure (such as PEG-PCL8636-PEI) determined by their hydrophilic and hydrophobic block ratio. The distinct structural architectures of copolymer are consistent between interface and self-assembly. Despite the disparity of constituent ratio, we discovered the arrangement of both chains guarantees balanced hydrophilic-hydrophobic ratio in self-assembly to form stable construction. Meanwhile, the structural differences were found to have significant influence on model drugs incorporation including docetaxel and siRNA. Taken together, these findings indicate the correlation between molecular arrangement and self-assembly and inspire us to tune block compositions to achieve desired nanostructure and drug loading.
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Dbait is a small double-stranded DNA molecule that has been utilized as a radiosensitizer to enhance the sensitivity of glioma to radiotherapy (RT). However, there is no effective drug delivery system to effectively overcome the blood-brain barrier (BBB). The aim of this study was to develop a gene delivery system by using the BBB and glioma dual-targeting and microenvironment-responsive micelles (ch-K(s-s)R8-An) to deliver Dbait into glioma for RT. Angiopep-2 can target the low-density lipoprotein receptor-related protein-1 (LRP1) that is overexpressed on brain capillary endothelial cells (BCECs) and glioma cells. In particular, due to upregulated matrix metalloproteinase 2 (MMP-2) in the tumor microenvironment, we utilized MMP-2-responsive peptides as the enzymatically degradable linkers to conjugate angiopep-2. The results showed that ch-K(s-s)R8-An micelles maintained a reasonable size (80-160 nm) with a moderate distribution and a decreased mean diameter from the cross-linking as well as exhibited low critical micelle concentration (CMC) with positive surface charge, ranging from 15 to 40 mV. The ch-K5(s-s)R8-An/pEGFP showed high gene transfection efficiency , improved uptake in glioma cells and good biocompatibility and . In addition, the combination of ch-K5(s-s)R8-An/Dbait with RT significantly inhibited the growth of U251 cells . Thus, ch-K5(s-s)R8-An/Dbait may prove to be a promising gene delivery system to target glioma and enhance the efficacy of RT on U251 cells.
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Objective To prepare baicalin-polyethylene glycol-poly (lactic-co-glycolic acid) copolymer (PEG-PLGA)-loaded nanomicelles, and study its in vitro drug release properties and tissue distributed in rats with acute myocardial ischemia. Methods The preparation process of baicalin PEG-PLGA nanomicelles was optimized by orthogonal test. The optimized baicalin PEG-PLGA nanomicelles were characterized by particle size, Zeta potential, and TEM electron microscopy. The in vitro release assay and tissue distribution of the acute myocardial ischemia rat model were used to evaluate this drug delivery system. Results The preferred preparation conditions for baicalin PEG-PLGA nanomicelles were a mass ratio of baicalin to PEG-PLGA at 1:10 with a rotary evaporator rotation rate of 80 r/min and a hydration temperature of 40 ℃. The optimized baicalin PEG-PLGA nanomicelle particle size was (18.5 ± 0.5) nm, the zeta potential was (-10.9 ± 0.7) mV, the drug loading was (7.9 ± 0.3)%, and the encapsulation efficiency was (86.2 ± 2.5)%. The critical micelle concentration of PEG-PLGA nanomicelles was 3.8 μg/mL by oxime assay. TEM showed that baicalin PEG-PLGA nanomicelles presented a spherical shape with uniform particle size, In vitro release test showed that baicalin PEG-PLGA nanomicelles had obvious sustained release characteristics; Tissue distribution test showed that the order of distribution of baicalin PEG-PLGA nanomicelles in normal rat organs was liver > spleen > heart > kidney > lung > brain, while the distribution of baicalin PEG-PLGA nanomicelles in acute myocardial ischemia model was liver > heart > spleen > kidney > brain. Compared with normal rats, the drug concentration in the heart of rats with acute myocardial ischemia showed a significant increase trend in all time periods, and the highest drug concentration at 120 min could reach (2 897 ± 135) ng/mL, the highest drug concentration of the heart in the normal rats was (2 411 ± 89) ng/mL, which indicated that the baicalin PEG-PLGA nanomicelles had good targeting in the acute myocardial ischemia zone. Conclusion Baicalin PEG-PLGA nanomicelles have good drug-loading properties, slow release in vitro, and can accumulate drugs in the ischemic myocardium, which has good cardiac targeting.
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Objective:To investigate the effect of surfactants on contact angle of pharmaceutical excipients and further study the effect of surfactants at different concentrations on the wettability of excipients and the effect of of surfactants and excipients at different proportions on the wettability of tablets. Methods:Different kinds of excipients were selected for tabletting,and surfactant solutions at different concentrations were prepared. The contact angle of the solutions on the surface of the tablets was measured by a contact angle tester. Results:The contact angle between the surfactants below the critical micelle concentrations and the tablets was the smallest and the wettability was the best. The change of the contact angle on the tablets with hydrophilic materials was less than that with hydropho-bic ones for most of the surfactants at the same concentration. Conclusion:After the addition of surfactants,the contact angle of excip-ient tablets significantly decreases, however, the contact angle will be stable after the amount of surfactants reaches a certain ratio, which shows significant reference value for tablet formula design.
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Objective: To design and synthesize a different molecular mass block copolymer of poly(L-phenylalanine)-b-poly(L-aspartic acid)(PPA-PAA). Methods: The L-phenylalanine and L-aspartic acid were used as raw materials to synthesize L-phenylalanine N-carboxy-α-amino acid anhydride and L-aspartic acid-β-benzylester N-carboxy-α-amino acid anhydride. The target compounds of amphiphilic block copolymer of PPA-PAA were synthesized by ring-opening polymerization. The critical micelle concentration of the amphiphilic polymer was determined by pyrene fluorescence probe method. Results: The copolymers of hydrophobic chain segment 500, 2000, and 4000 were synthesized and the structures were confirmed by hydrogen nuclear magnetic resonance and Fourier transformed infrared. The critical micelle concentration of polymers changed with adjusting the feed ratio of PPA to PAA. Conclusion: The results show that the longer the hydrophobic chain segment of PPA is, the smaller the critical micelle concentration of polymers. The results lay the groundwork for further studying the stabilizing effect of the drug polymer nanoparticles with different properties.
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Objective To design and synthesize a different molecular mass block copolymer of poly(L-phenylalanine)-b-poly (L-aspartic acid)(PPA-PAA). Methods The L-phenylalanine and L-aspartic acid were used as raw materials to synthesize L-phenyl?alanine N-carboxy-ɑ-amino acid anhydride and L-aspartic acid-β-benzylester N-carboxy-ɑ-amino acid anhydride. The target com?pounds of amphiphilic block copolymer of PPA-PAA were synthesized by ring-opening polymerization. The critical micelle concentra?tion of the amphiphilic polymer was determined by pyrene fluorescence probe method. Results The copolymers of hydrophobic chain segment 500,2000,and 4000 were synthesized and the structures were confirmed by hydrogen nuclear magnetic resonance and Fouri?er transformed infrared. The critical micelle concentration of polymers changed with adjusting the feed ratio of PPA to PAA. Conclu?sion The results show that the longer the hydrophobic chain segment of PPA is,the smaller the critical micelle concentration of poly?mers. The results lay the groundwork for further studying the stabilizing effect of the drug polymer nanoparticles with different proper?ties.
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The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells, which is usually caused by abnormal gene expression. RNA interference mediated by siRNA and miRNA can selectively knock down the carcinogenic genes by targeting specific mRNAs. Therefore, combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy. Due to poor stability and solubility associated with gene agents and drugs, suitable protective carriers are needed and have been widely researched for the co-delivery. In this review, we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents, as well as the advances in co-delivery systems.
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A resonance light scattering(RLS) method for the determination of critical micelle concentration(CMC) of sodium dodecyl benzene sulfonate(SDBS) was proposed. Under room temperature, the RLS intensity of the SDBS system increased with increasing SDBS concentration. And when the concentration of SDBS approached CMC, the RLS intensity had increased sharply. The RLS peaks were appeared at 330 nm and 396 nm, respectively. The plot of the RLS intensity at 396 nm versus SDBS concentration was S-Curve. The concentration of SDBS at the intersection point of two tangents to S-curve was considered as SBDS CMC. This result was consistent with the results of the pyrene probe fluorescence spectrometry and electrical conductivity method. The influences of the concentration of Ca2+ on the aggregation behave of SDBS and SDBS-emulsion OP(OP) systems were studied by the RLS method. The results indicated that the mixed
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Understanding the membrane solubilization process and finding effective solubilizing agents are crucial challenges in biochemical research. Here we report results on the interaction of the novel linear alkylamido propyl dimethyl amino propanosulfonate detergents, ASB-14 and ASB-16, with human erythrocyte membranes. An estimation of the critical micelle concentration of these zwitterionic detergents (ASB-14 = 100 µM and ASB-16 = 10 µM) was obtained using electron paramagnetic resonance. The amount of proteins and cholesterol solubilized from erythrocytes by these detergents was then determined. The hemolytic activities of the ASB detergents were assayed and the detergent/lipid molar ratios for the onset of hemolysis (Re sat) and total lysis (Re sol) were calculated, allowing the determination of the membrane binding constants (Kb). ASB-14 presented lower membrane affinity (Kb = 7050 M-1) than ASB-16 (Kb = 15610 M-1). The amount of proteins and cholesterol solubilized by both ASB detergents was higher while Re sat values (0.22 and 0.08 detergent/lipid for ASB-14 and ASB-16, respectively) were smaller than those observed with the classic detergents CHAPS and Triton X-100. These results reveal that, besides their well-known use as membrane protein solubilizers to enhance the resolution of two dimensional electrophoresis/mass spectrometry, ASB-14 and ASB-16 are strong hemolytic agents. We propose that the physicochemical properties of ASB detergents determine their membrane disruption efficiency and can help to explain the improvement in the solubilization of membrane proteins, as reported in the literature.