Molecular implications in the nanoencapsulation of the anti-tuberculosis drug rifampicin within flower-like polymeric micelles

Tuberculosis (TB) is the second most deadly infectious disease behind the Human Immunodeficiency Virus (HIV). An effective pharmacotherapy has been available for more than 5 decades. However, the length of the treatment and the pill burden result in low patient compliance and adherence to the regimens. Nanotechnologies can overcome these basic technological drawbacks. The present work explored the molecular implications governing the encapsulation and water solubilization of RIF within flower-like micelles of poly(epsilon-caprolactone)-b-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) block copolymers. Ten derivatives of different molecular weight and hydrophobic/hydrophilic caprolactone/ethylene oxide ratio (CL/EO) were synthesized by a fast and high-yield Microwave-Assisted Polymer Synthesis (MAPS) technique; CL/EO values are determined by taking the ratios of the number of repeating units in the PCL and the PEG segments. The aggregation behavior of the copolymers was thoroughly investigated by means of surface tension (critical micellar concentration), dynamic light scattering (size, size distribution and zeta potential) and transmission electron microscopy (morphology). In general, the greater the central PEG segment, the larger the micelles formed. The physical stability was intimately associated with the molecular weight and the composition. Then, the encapsulation of RIF in the different copolymer families was evaluated, and the physical stability of the drug-loaded aggregates characterized. The micellar size appears as the most crucial property, this phenomenon being primarily controlled by the molecular weight of the PEG central block. Having expressed this, sufficiently high CL/EO ratios (and long PCL segments) are also demanded to attain stable micellar systems with cores that are large enough to host the bulky RIF molecule.     

Indium nitride crystals with flower-like structure

Preparation of indium nitride at atmospheric pressure has been examined by means of halide chemical vapour deposition; from the SEM observations of the crystals deposited onto an Si(100) substrate it was found that they showed flower-like structure.     

蒲公英黄酮抗氧化活性的构效关系分析

蒲公英作为传统的中药材,具有抗氧化、抗肿瘤、抗菌、抗炎等多种药用价值。黄酮是蒲公英发挥抗氧化作用的重要活性成分。蒲公英黄酮抗氧化性能的实验研究备受关注,然而从分子水平对蒲公英黄酮结构与抗氧化活性之间的内在关系缺乏系统的研究。本文借助于密度泛函理论,针对蒲公英中5种重要的黄酮化合物(槲皮素、芦丁、木犀草素、芹菜素、香叶木素),通过优化结构参数、捕获DPPH自由基的热力学能量分析,NBO电荷分布、半醌自由基的自旋密度分析等方面深入探讨了蒲公英黄酮化合物抗氧化活性的构效关系及内在规律。结果表明：5种蒲公英黄酮化合物抗氧化活性为芦丁>槲皮素>木犀草素>>香叶木素>芹菜素,酚羟基的位置是影响蒲公英黄酮抗氧化活性差异的主要因素。蒲公英黄酮不同位点抗氧化活性的高低与其酚羟基上H原子的电荷分布、黄酮自由基的稳定性成正比关系,自由基单电子的离域程度和分子内氢键的稳定化作用共同决定了B环4’-OH是蒲公英黄酮的关键活性位点。     

Fabrication of flower-like silver structures through anisotropic growth

Using a simple chemical reaction, a new nanostructure of silver, which we call a "flower-like silver structure", is produced. The flower-like silver structure consists of a silver core and many rod-like tips protruding out in three dimensions. Besides common face-centered-cubic (FCC) phase of silver, there exists hexagonal-close-packed (HCP) phase in these tips. The appearance of HCP silver is the result of rapid growth of silver nuclei when using CH(2)O or C(2)H(4)O as the reducing agent. The formation of the rod-like tips is caused by the anisotropic growth determined by the HCP phase and the directing role of formic acid, which is the oxidation product of CH(2)O. It is also found that the concentration of reactants, the kind of reducing agents and the sequence of adding reactants can influence the morphology and phase constitution of the final products.     

Studies on micelles

Summary It is shown by the absorption intensity that the micellar volume increases continuously from the CMC in wider surfactant concentration range. Considering many experimental results reported, is presented the model of constant particle concentration above the CMC for the aqueous micellar solutions as the first approximation. The qualitative reasons to present this model are mentioned.

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Zusammenfassung Die Absorption weist darauf hin, da? das Mizellvolumen von der CMC in weitem Konzentrationsbereich grenzfl?chenaktiver Substanzen ansteigt. Aus vielen gegebenen Versuchsdaten wird ein Modell konstanter Partikelkonzentration oberhalb der CMC in gleichmizellaren L?sungen als erste N?herung gefolgert. Die qualitativen Gründe für ein solches Modell sind genannt.

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Series IV.Sata, N. andH. Sasaki, Kolloid-Z.153, 41 (1957).

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The author wishes to thank Prof.N. Sata for his encouragement and discussion and Dr.H. Okuyama for general discussion and also the author is indebted to Mr.S. Saito for the purification of octadecyl trimethyl ammonium chloride and to Mr.S. Fukushima for the discussion about stray light.     

Temperature-sensitive dendritic micelles

Syntheses up to three generations have been achieved of biaryl-based amphiphilic dendrons with a charge-neutral pentaethylene glycol as the hydrophilic part and a decyl chain as the hydrophobic part. Studies on the temperature-dependent characteristics revealed that these dendrons exhibit a generation-dependent lower critical solution temperature (LCST). This behavior is attributed to the combination of the amphipathic nature of the hydrophilic pentaethylene glycol side chain and dendritic effect. Interestingly, this biaryl-based scaffold also maintains the ability to form a micelle-like assembly in polar solvents and an inverted micelle-like assembly in apolar solvents. Polarity of the dendritic interior was investigated using dye-based microenvironment studies. The aggregation behavior of these micelles was analyzed by fluorescence spectroscopy and dynamic light scattering. Critical micelle concentrations (CMC) of these assemblies were investigated using fluorescence excitation spectra of the sequestered guest molecule, pyrene.     

双波长分光光度法测定蒲公英中总黄酮

建立了测定蒲公英中总黄酮含量的双波长分光光度法。实验结果表明,以Al(NO3)3为显色剂,在测定波长为510nm,参比波长为590nm的条件下,总黄酮的质量浓度与吸光度差值△A在8.0~40.0μg/mL范围呈良好线性关系,相关系数r=0.9993,回收率为98.75%~102.30%,相对标准偏差(RSD)为1.24%。该方法操作简便,稳定可靠,重现性好。     

pH-switchable wormlike micelles

A novel pH-switchable wormlike micellar system was prepared by mixing N-erucamidopropyl-N,N-dimethylamine and maleic acid with molar ratio of 2 : 1. The viscosity of the micellar solution is switchable via tuning the pH through the addition of minor acid or base. Such a system possesses the characteristics of a facile, rapid, cost-effective reversible process and recyclable cheaper materials.     

The fabrication of flower-like graphene/octadecylamine composites

Three-dimensional flower-like nanomaterials have wide application due to the large specific surface area. In this letter, the morphology of octadecylamine (ODA) from several common solvents is studied and it is found that from the chloroform and acetone solution, ODA assembles into petal-like structure, which further forms the spherical or flower-like architecture. Furthermore, the composite materials incorporated reduced graphene oxide (rGO) and ODA could well keep the flower-shaped structure of ODA. XRD results show that the introduction of graphene has little influence on the structure of ODA and contact angle test indicates good hydrophobic performance of the rGO/ODA material.     

Evolution of multicompartment micelles to mixed corona micelles using solvent mixtures

Miktoarm star triblock copolymers mu-[poly(ethylethylene)][poly(ethylene oxide)][poly(perfluoropropylene oxide)] self-assemble in dilute aqueous solution to give multicompartment micelles with the cores consisting of discrete poly(ethylethylene) and poly(perfluoropropylene oxide) domains. Tetrahydrofuran is a selective solvent for both the poly(ethylethylene) and poly(ethylene oxide) blocks, and thus in tetrahydrofuran mixed corona micelles are favored with poly(perfluoropropylene oxide) cores. The introduction of tetrahydrofuran into water induces an evolution from multicompartment micelles to mixed corona [poly(ethylethylene) + poly(ethylene oxide)] micelles, as verified by dynamic light scattering and nuclear magnetic resonance spectroscopy. A mixed solvent containing 60 wt % tetrahydrofuran corresponds to the transition point, as verified by analysis of a poly(ethylethylene)-poly(ethylene oxide) diblock copolymer in the same solvent mixtures. Furthermore, cryogenic transmission electron microscopy suggests that, as the poly(ethylethylene) block transitions from the core to the corona, the micelle morphologies evolve from disks to oblate ellipsoid micelles (with some vesicles), with worms and spheres evident at intermediate compositions.     

Polyaniline nanobelts, flower-like and rhizoid-like nanostructures by electrospinning

Nanobelts, flower-like and rhizoid-like nanostructures of pure polyaniline （PANI） doped with sulfuric acid or hydrochloric acid were prepared via electrospinning by using a coagulation bath as the collector after optimizing the fabrication parameters. The morphologies of these nanostructures were characterized by scanning electron microscope （SEM）. The possible formation mechanisms were discussed.     

Fabrication of flower-like silver nanoparticles for surface-enhanced Raman scattering

The flower-like silver nanoparticles have been synthesized by reducing silver nitrate (AgNO₃) with ascorbic acid (AA) as the reductant and polyvinyl pyrrolidone (PVP) as the capping agent under vigorous stirring. Such flower-like nanoparticles are aggregates of small nanoplates and nanorods. They were tested as substrates for the surface-enhanced Raman scattering (SERS), showing high sensitivity for detecting Rhodamine 6G (R6G) at a concentration as low as 10^-7 mol/L. It has been found that replacing mechanical stirring with ultrasound sonication would drastically change the particle morphology, from flower-like nanoparticles to well-dispersed smaller nanoparticles. Furthermore, when trace amounts of NaCl were added into the reagents, well-dispersed Ag nanoparticles formed even in vigorous stirring. These phenomena can be explained with the diffusion and reactant supply during nucleation and growth of Ag nanoparticles.     

Polymerized micelles with compartments

Multicompartment micelles with distinct hydrophobic microdomains having different properties have been realized via micellar polymers bearing hydrocarbon and fluorocarbon fragments. In aqueous solution, such polymers can self-organize into coexisting hydrocarbon and fluorocarbon microdomains that selectively solubilize different hydrophobes. The most efficient approach uses block copolymer polysoaps, but simpler designs may be possible.     

Scattering from polymer-like micelles

Polymer-like micelles are analogs to polymer solutions and provide an exciting class of materials for both applications and fundamental understanding of polyelectrolyte systems. Small angle neutron and X-ray scattering have been key to the characterization of these materials from the first observations of linear micelle growth. As new materials are developed, these techniques continue to be utilized and combined with other analytical tools to characterize the length and time scales of polymer-like micelle behavior. Recent reports on the use of small-angle scattering to characterize polymer-like and wormlike micelles are reviewed, with focus on new materials, improvements in analytical approaches and anisotropic structures.     

Surface active inverse micelles

Surface tension of solutions of a commercial non-ionic surfactant, Laureth 4, and two hydrocarbons, decane and hexadecane, with added water, was determined using a de Nouy ring. The results showed a reduction of surface tension with added water, confirming an earlier suggestion of surface activity of inverse micelles. The surface activity is ascribed to the orientation of the hydrocarbon chains in the inverse micelle, giving a preferential location of the low surface free-energy methyl groups at the surface of the micelle. The location of the micelle at the surface was estimated from calculations of the minimum in the free energy when a solid particle was transferred across the liquid–air interface. This energy showed a distinct minimum indicating the location of the particle. However, the conditions for that minimum to occur were such that no balance of surface tension forces along the liquid surface to air could occur. The reason for that apparent discrepancy is discussed.     

Molecule-responsive block copolymer micelles

Ring-opening metathesis polymerization was used to generate an ABC triblock copolymer, containing complementary diamidopyridine (DAP) and thymine (THY) outer blocks, which assembles into spherical aggregates held together by DAP-THY noncovalent interactions. Addition of THY-containing small guest molecules results in complete opening and deaggregation of the block copolymer micelle. This molecular recognition and macroscopic response shows high selectivity to the guest structure, and tolerates only a small amount of conformational mobility in the THY guest. On the other hand, addition of a small DAP-containing guest does not break the aggregates, but instead, results in new micelles which show a different selectivity profile from the parent morphology. We have examined the effect of a number of structural features in the block copolymers, on both the extent and selectivity of their macroscopic response to guests (that is, opening of the micelle). This study has resulted in a set of structural guidelines, which help in the design of effective molecule-responsive micelles for applications in selective drug delivery, sensing, and surface patterning.     

Bactericidal block copolymer micelles

Block copolymer micelles with bactericidal properties were designed to deactivate pathogens such as E. coli bacteria. The micelles of PS‐b‐PAA and PS‐b‐P4VP block copolymers were loaded with biocides TCMTB or TCN up to 20 or 30 wt.‐%, depending on the type of antibacterial agent. Bacteria were exposed to loaded micelles and bacterial deactivation was evaluated. The micelles loaded with TCN are bactericidal; bacteria are killed in less than two minutes of exposure. The most likely interpretation of the data is that the biocide is transferred to the bacteria by repeated micelle/bacteria contacts, and not via the solution.

     

Mobility op polymer micelles

The nanosecond mobility of polymer micelles in aqueous solution of poly(N-propylmethacrylamide) and that of reversed micelles of a surfactant in organic solvents were studied by polarized luminescence. The factors affecting the polymer micelles formation and the effect of polymers solubilized in systems of reversed micelles of a surfactant on their relaxation properties were established.