Isamu Akiba

Hydrophobic Molecules Infiltrating into the Poly(ethylene glycol) Domain of the Core/Shell Interface of a Polymeric Micelle: Evidence Obtained with Anomalous Small-Angle X-ray Scattering

Polymeric micelles have been extensively studied as nanoscale drug carriers. Knowing the inner structure of polymeric micelles that encapsulate hydrophobic drugs is important to design effective carriers. In our study, the hydrophobic compound tetrabromocathecol (TBC) was chosen as a drug-equivalent model molecule. The bromine atoms in TBC act as probes in anomalous small-angle X-ray scattering (ASAXS) allowing for its localization in the polymeric micelles whose shape and size were determined by normal small-angle X-ray scattering (SAXS). Light scattering measurements coupled with field flow fractionation were also carried out to determine the aggregation number of micelles. A core-corona spherical model was used to explain the shape of the micelles, while the distribution of bromine atoms was explained with a hard-sphere model. Interestingly, the radius of the spherical region populated with bromine atoms was larger than the one of the sphere corresponding to the hydrophobic core of the micelle. This result suggests that the TBC molecules infiltrate the PEG hydrophilic domain in the vicinity of the core/shell interface. The results of light scattering and SAXS indicate that the PEG chains at the shell region are densely packed, and thus the PEG domain close to the interface has enough hydrophobicity to tolerate the presence of hydrophobic compounds.

Encapsulation of a Hydrophobic Drug into a Polymer-Micelle Core Explored with Synchrotron SAXS

Synchrotron small-angle X-ray scattering (SAXS) at the SPring-8 40B2 and 45XU beamlines was carried out on aqueous solutions of (PEG-P(Asp(Bzl))): partially benzyl-esterified poly(ethylene glycol)-block-poly(aspartic acid) with LE540 loaded up to 8.3 wt %, where LE540 is a very hydrophobic retinoid antagonist drug. The scattering profiles showed characteristic features for core-shell spherical micelles, confirming that P(Asp(Bzl)) forms a hydrophobic core and PEG forms a hydrophilic shell. Before the addition of LE540, a diffraction peak was observed around q = 4 nm(-1), where q is the magnitude of the scattering vector. This peak can be attributed to ordering between alpha-helices made of P(Asp(Bzl)), the so-called nonspecific hexatic arrangement. The P(Asp(Bzl)) helices disappeared as LE540 was added. This result can be interpreted by assuming a uniform distribution of LE540 in the core. By use of a core-shell spherical micelle model, the SAXS data could be well fitted for all of the samples. The analysis indicated that the core radius increases sigmoidally from 5.9 to 6.9 nm upon addition of LE540 whereas the shell radius stayed at 12.5-12.8 nm. The aggregation number that is the average number of PEG-P(Asp(Bzl))s consisting of one micelle slightly increased from 145 to 182.

Phase behavior and pressure sensitive adhesive properties in blends of poly(styrene-b-isoprene-b-styrene) with tackifier resin

Phase behavior of poly(styrene-b-isoprene-b-styrene) (SIS)/tackifier resin blends were investigated by thermal analysis, morphological observation and cloud point measurements. In the heating process, the blends showed lower critical solution temperature phase transition at around 150°C and upper critical solution temperature (UCST) phase transition at around 200°C. However, in the cooling process, only UCST phase transition was observed in the SIS/tackifier resin blends. In addition, it was found that properties of the pressure sensitive adhesive in SIS/tackifier resin blends were changed with annealing temperature corresponding to the phase behavior.

A Stimulus-Responsive Shape-Persistent Micelle Bearing a Calix[4]arene Building Block: Reversible pH-Dependent Transition between Spherical and Cylindrical Forms

A series of cationic calix[4]arene-based lipids with alkyl chains of varying length were newly synthesized, and the ones with propyl and hexyl tails, denoted by CaL[4]C3 and C6, respectively, were found to form spherical micelles at low pH (protonated state of the amine headgroup). Upon deprotonation with increasing pH, CaL[4]C3 showed a sphere-to-cylinder transition, while CaL[4]C6 changed from sphere, to cylinder, to monolayer vesicle. Synchrotron small-angle X-ray scattering (SAXS) patterns from both spherical and cylindrical CaL[4]C3 micelles exhibited a sharp intensity minimum, indicating shape monodispersity. The monodispersity of the CaL[4]C3 spherical micelles was further confirmed by analytical ultracentrifugation (AUC). SAXS, AUC, and static light scattering agreeingly indicated an aggregation number of 6. In contrast, CaL[4]C6 exhibited polydispersity with an average aggregation number of 12. When the number of carbons of the alkyl chain was increased to 9 (CaL[4]C9), cylinder formed at low pH, while at high pH, no clear morphology could be observed. The present results indicate that a very precise combination of tail length, head volume, and rigidity of the building block is required to produce shape-persistent micelles and that the shape-persistence can be maintained upon a structural transition. An attempt to reconstruct a molecular model for the spherical CaL[4]C3 micelle was made with an ab initio shape determining program.

Composition dependence of the micellar architecture made from poly(ethylene glycol)-block-poly(partially benzyl-esterified aspartic acid).

Poly(ethylene glycol)-block-poly(partially benzyl-esterified aspartic acid), denoted by PEG-P(Asp(Bzl)), is one of the most examined blockcopolymers for drug carriers. However, little is known about fundamental physical properties. Nine samples of PEG-P(Asp(Bzl)) with different benzylation fractions (F(Bzl)) and aspartic chain lengths (DP(Asp)) were synthesized, and the aggregation number (N(agg)), core radius (R(C)), and other structural parameters were determined with combination of light scattering and synchrotron X-ray small-angle scattering. The major factor to determine N(agg) and R(C) was found to be F(Bzl), i.e., the hydrophobic nature of the core, even though F(Bzl) was changed in the relatively small composition range from 66 to 89 mol %. When we compared the data for the same F(Bzl), the scaling theory was consistent with the core chain length dependence of both core and micelle sizes. The overcrowding nature of the tethered PEG chains on the micelles was increased about 1.3-2.9 times with increasing N(agg) compared with the unperturbed state in solutions.

Access to different nanostructures via self-assembly of thiourea-containing PEGylated amphiphiles.

Readily water-soluble PEGylated amphiphiles containing bis-thiourea-based molecular recognition units at the interface of hydrophobic and hydrophilic blocks are developed. Self-assembly of these amphiphiles is found to be dependent on the exact chemical composition of the hydrophobic component. Elongated, spherical, and disk-like micelles are formed with the change in hydrophobic group from stearyl (2A), oleyl (2B), and dodecanol (2C), respectively. The length of the rod-like elongated micelles formed by 2A could be tuned by thermal treatment as well. Synthesis and detailed structural characterization of these amphiphiles by TEM, DSC, synchrotron SAXS techniques are reported. Organic solvent-free direct aqueous encapsulation of doxorubicin, an anticancer drug into these nanostructures is demonstrated.

Supramolecular structures of benzyl amine derivate/DNA complexes explored with synchrotron small angle X-ray scattering at SPring-8

Relationship between the transfection efficiency and the supramolecular structure of the lipoplexes consisting of DNA, a benzyl amine derivative (BA), and two neutral co-lipids (DOPE and DLPC) were examined. At a composition of BA:DOPE:DLPC = 1:2:1; where the highest efficiency was attained, SAXS showed that the micelles before adding DNA formed a hexagonally-packed cylinder and addition of DNA improved the packing order. This phenomenon may be interpreted by intercalation of DNA between the preformed micellar cylinders. At a composition of BA: DLPC=1:1, where the lowest efficiency was observed, the micelle adopted a spherical form and addition of DNA induce a structural transition from the sphere to a hexagonally packed cylinder, and then a lamellar form. Fitting with a multilayer model suggested that DNA was included into the hydrophobic layer of the complex. Comparison of these two compositions suggests that difference in the DNA location in the lipoplex is related to the transfection efficiency.

Compatibilizing effects of poly(ethylene-block-methyl methacrylate) on blends of polyethylene and poly(4-vinylphenol)

Compatibilizing effects of polyethylene‐poly(methyl methacrylate) diblock copolymer (P(E-b-MMA)) on immiscible blends of polyethylene (PE) and poly-4-vinylphenol (PVPh) have been investigated by scanning electron microscopy (SEM) and optical microscopy (OM). In OM observation, it was found that there was coalescence of the PVPh particles in the PE/PVPh blends without P(E-b-MMA) at 1808C. On the contrary, the coalescence of the PVPh particles was not observed in the PE/PVPh blends added with P(E-b-MMA) at 1808C. In addition in the SEM observation, when small amount of P(E-b-MMA) are added to the PE/PVPh blends, the size of PVPh particles decreased drastically and their size distribution become narrower with increasing P(E-b-MMA) content. Therefore it has been concluded that P(E-b-MMA) acts as the compatibilizer in the PE/PVPh blends. q 2000 Elsevier Science Ltd. All rights reserved.

Platonic Micelles: Monodisperse Micelles with Discrete Aggregation Numbers Corresponding to Regular Polyhedra

The concept of micelles was first proposed in 1913 by McBain and has rationalized numerous experimental results of the self-aggregation of surfactants. It is generally agreed that the aggregation number (Nagg) for spherical micelles has no exact value and a certain distribution. However, our studies of calix[4]arene surfactants showed that they were monodisperse with a defined Nagg whose values are chosen from 6, 8, 12, 20, and 32. Interestingly, some of these numbers coincide with the face numbers of Platonic solids, thus we named them “Platonic micelles”. The preferred Nagg values were explained in relation to the mathematical Tammes problem: how to obtain the best coverage of a sphere surface with multiple identical circles. The coverage ratio D(N) can be calculated and produces maxima at N = 6, 12, 20, and 32, coinciding with the observed Nagg values. We presume that this “Platonic nature” may hold for any spherical micelles when Nagg is sufficiently small.

Crystallization in Microdomains of a Block Copolymer Comprising Semicrystalline Block Observed by Simultaneous Measurement of SAXS and WAXS with H v‐SALS or DSC

Abstract Semicrystalline block copolymers provide us with a fascinating model for studying the kinetics of crystallization. We performed the simultaneous measurement of small‐ (SAXS) and wide‐angle (WAXS) x‐ray scattering (SWAXS) with differential scanning calorimetry (DSC), or SWAXS with small‐angle light scattering (H v‐SALS). The specimen used was polyethylene‐b‐poly(ethylene propylene) (PE‐b‐PEP) with the molecular weight of 44,200. The PE block has the melting point (T m) at 108°C. We observed the time evolution of crystallization in the lamellar microdomains of PE‐b‐PEP after a temperature drop from 180°C (≫T m) to a variety of temperatures slightly below T m. The exothermic signal was observed by DSC right after the temperature drop, while the four‐leaf‐clover pattern of H v‐SALS and the SAXS peaks due to the lamellar microdomains were observed several minutes after the temperature equilibration. The WAXS peaks of (110) and (200) reflection were almost simultaneously detected with the H v‐SALS and the SAXS peaks at crystallization temperature of 100°C. With the crystallization temperature closer to T m, the WAXS crystalline signals showed up with longer time lag after the H v‐SALS and the SAXS peaks began to appear. Interestingly, these phenomena are interpreted as that long‐range order of density fluctuation up to the order of micrometers was generated prior to the formation of crystals with partially ordered phase rather than the instantaneous crystalline nucleation.