Amphiphilic Block Copolymer Micelles for Gene Delivery

Gene therapy is a promising method to treat acquired and inherited diseases by introducing exogenous genes into specific recipient cells. Polymeric micelles with different nanoscopic morphologies and properties hold great promise for gene delivery system. Conventional cationic polymers, poly(ethyleneimine)(PEI), poly(L-lysine)(PLL), poly(2-dimethyla-minoethyl methacrylate)(PDMAEMA) and novel cationic polymers poly(2-oxazoline)s(POxs), have been incorporated into block copolymers and decorated with targeting moieties to enhance transfection efficiency. In order to minimize cytotoxicity, nonionic block copolymer micelles are utilized to load gene through hydrophilic and hydrophobic interactions or covalent conjugations, recently. From our perspective, properties(shape, size, and mechanical stiffness, etc.) of block copolymer micelles may significantly affect cytotoxicity, transfection efficiency, circulation time, and load capacity of gene vectors in vivo and in vitro. This review briefly sums up recent efforts in cationic and nonionic amphiphilic polymeric micelles for gene delivery.     

聚乙二醇嵌段树枝状聚赖氨酸共聚物的合成及其基因载体研究

采用液相多肽合成法制备得到窄分子量分布、结构可控的生物相容性聚乙二醇嵌段共聚树枝状聚赖氨酸阳离子功能大分子(PEG-b-Dendritic PLL). 运用¹H NMR核磁共振、凝胶电泳以及荧光淬灭滴定手段对所得阳离子两嵌段大分子的化学结构及其与质粒DNA (pDNA)结合作用与复合行为进行了研究. 结果表明聚乙二醇嵌段树枝状聚赖氨酸与pDNA分子可以在缓冲溶液中形成稳定的胶束, pDNA与阳离子树枝赖氨酸嵌段通过静电相互作用形成胶束核, 其水溶性聚乙二醇嵌段形成水溶性胶束壳, 提高了阳离子大分子/pDNA复合胶束的稳定性. 同时发现随着阳离子嵌段树枝状赖氨酸代数的增加, 阳离子两嵌段大分子与pDNA的结合作用增强, 有利于其作为基因转染生物功能载体的应用.     

Reversible Photoswitching in Poly(2-oxazoline) Nanoreactors

This contribution reports light responsive catalytic nanoreactors based on poly(2-oxazoline) diblock copolymers. The hydrophobic block of the copolymer is a random copolymer consisting of a spiropyran functionalized 2-oxazoline (SPOx) and 2-(but-3-yn-1-yl)-4,5-dihydrooxazole (ButynOx), while the hydrophilic block is based on 2-methyl-2-oxazoline (MeOx). The block copolymer is terminated with tris(2-aminoethyl) amine (TREN) that serves as catalyst in a Knoevenagel condensation. Four block copolymers with different ButynOx/SPOx and hydrophilic/hydrophobic ratios are synthesized and self-assembled through solvent exchange. Micelles and vesicles of various sizes are observed by TEM, which undergo morphological and size changes in response to irradiation with UV light. We hypothesize that these transformations in the nanostructures are caused by increases in the hydrophilicity of the hydrophobic block when spiropyran (SP) isomerizes to merocyanine (MC) in the presence of UV light. The reversible transition from micellar to vesicular nanoreactors resulted in increased reaction kinetics through improved substrate accessibility to the catalytic site, or termination of the catalytic reaction due to polymer precipitation. These nanoreactors present a promising platform towards photoregulating reaction outcomes based on changes in nanostructure morphology.     

Synthesis of poly(styrene-tetrahydrofuran-2-methyl-2-oxazoline) triblock and graft copolymers

Poly[styrene (ST)-tetrahydrofuran (THF)-2-methyl-2-oxazoline(MeOz)] triblock and graft copolymers were prepared by ionic polymerizations. Poly(ST-THF) graft copolymers were synthesized by coupling of ST-4-vinylpyridine (4VP) copolymer with a large excess of PTHF dication. The ion coupling of PST dianion with PTHF dication was accompanied by the side reaction (abstraction of α proton of oxonium ion). After tosylation of terminal hydroxyl groups of PTHF blocks, cationic copolymerizations of MeOz with poly(ST-THF) block and graft copolymers were carried out, and characteristics of produced copolymers were investigated in some detail.     

Size- and Surface- Dual Engineered Small Polyplexes for Efficiently Targeting Delivery of siRNA

Though siRNA-based therapy has achieved great progress, efficient siRNA delivery remains a challenge. Here, we synthesized a copolymer PAsp(-N=C-PEG)-PCys-PAsp(DETA) consisting of a poly(aspartate) block grafted with comb-like PEG side chains via a pH-sensitive imine bond (PAsp(-N=C-PEG) block), a poly(l-cysteine) block with a thiol group (PCys block), and a cationic poly(aspartate) block grafted with diethylenetriamine (PAsp(DETA) block). The cationic polymers efficiently complexed siRNA into polyplexes, showing a sandwich-like structure with a PAsp(-N=C-PEG) out-layer, a crosslinked PCys interlayer, and a complexing core of siRNA and PAsp(DETA). Low pH-triggered breakage of pH-sensitive imine bonds caused PEG shedding. The disulfide bond-crosslinking and pH-triggered PEG shedding synergistically decreased the polyplexes’ size from 75 nm to 26 nm. To neutralize excessive positive charges and introduce the targeting ligand, the polyplexes without a PEG layer were coated with an anionic copolymer modified with the targeting ligand lauric acid. The resulting polyplexes exhibited high transfection efficiency and lysosomal escape capacity. This study provides a promising strategy to engineer the size and surface of polyplexes, allowing long blood circulation and targeted delivery of siRNA.     

Plasmid DNA complexation with phosphorylcholine diblock copolymers and its effect on cell transfection

We examined a series of novel cationic MPC-based (2-methacryloyloxyethyl phosphorylcholine) copolymers as vectors for gene delivery, with emphasis on the assessment of the effects of the charge ratio (administered via pH variation) on the complex (polyplex) formation and the subsequent transfection efficiency. A combination of electrophoresis, dynamic light scattering, and small angle neutron scattering was used to characterize the structure and charge distribution of the polyplexes formed between the copolymer and the luciferase plasmid DNA. Polymers with larger hydrophobic side chains had lower p K a values and tended to aggregate more strongly. For a given copolymer, electrostatic interaction was the main driving force for the formation of the nanopolyplexes. When the cationic copolymers were in excess, the majority of the polyplexes formed was neutral, and only a small faction of them carried net positive charges. Polyplexes formed under excess copolymer protected the DNA from restriction enzyme digestion. As the copolymers were weak polyelectrolytes, the pH had a distinct effect on the structure and charge distribution of the polyplexes formed. Below the p K a, the copolymers were found to bind with the plasmid DNA in the form of unimers, while above the p K a, the copolymers self-aggregated and complexed with DNA in the form of micelles. It was subsequently found that unimer/DNA polyplexes were far more effective in the transfection of HEK293 cells than micellar DNA polyplexes. The results thus revealed that different hydrophobicities of the side chains in the copolymer series led to different nanostructuring and charge characteristics, which had a consequential effect on the transfection efficiency. This study provided useful insight into the molecular processes underlying polyplex formation and demonstrated a strong link between structural and physical properties of polyplexes and cell transfection efficiency.     

New amphiphilic diblock copolymers: surfactant properties and solubilization in their micelles

Several series of amphiphilic diblock copolymers are investigated as macrosurfactants in comparison to reference low-molar-mass and polymeric surfactants. The various copolymers share poly(butyl acrylate) as a common hydrophobic block but are distinguished by six different hydrophilic blocks (one anionic, one cationic, and four nonionic hydrophilic blocks) with various compositions. Dynamic light scattering experiments indicate the presence of micelles over the whole concentration range from 10(-4) to 10 g x L(-1). Accordingly, the critical micellization concentrations are very low. Still, the surface tension of aqueous solutions of block copolymers decreases slowly but continuously with increasing concentration, without exhibiting a plateau. The longer the hydrophobic block, the shorter the hydrophilic block, and the less hydrophilic the monomer of the hydrophilic block is, the lower the surface tension is. However, the effects are small, and the copolymers reduce the surface tension much less than standard low-molar-mass surfactants. Also, the copolymers foam much less and even act as anti-foaming agents in classical foaming systems composed of standard surfactants. The copolymers stabilize O/W emulsions made of methyl palmitate as equally well as standard surfactants but are less efficient for O/W emulsions made of tributyrine. However, the copolymer micelles exhibit a high solubilization power for hydrophobic dyes, probably at their core-corona interface, in dependence on the initial geometry of the micelles and the composition of the block copolymers. Whereas micelles of copolymers with strongly hydrophilic blocks are stable upon solubilization, solubilization-induced micellar growth is observed for copolymers with moderately hydrophilic blocks.     

Preparation and properties of poly(alkyl vinyl ether-2-ethyl-2-oxazoline) diblock copolymers

A method for the synthesis of well-defined poly(alkyl vinyl ether–2-ethyl-2-oxazoline) diblock copolymers with hydrolytically stable block linkages has been developed. Monofunctional poly(alkyl vinyl ether) oligomers with nearly Poisson molecular weight distributions were prepared via a living cationic polymerization method using chloroethyl vinyl ether together with HI/ZnI₂ as the initiating system and lithium borohydride as the termination reagent. Using the resultant chloroethyl ether functional oligomers in combination with sodium iodide as macroinitiators, 2-ethyl-2-oxazoline was polymerized in chlorobenzene/NMP to afford diblock copolymers. A series of poly(methyl vinyl ether–2-ethyl-2-oxazoline) diblock materials were found to have polydispersities of ≈ 1.3–1.4 and are microphase separated as indicated by two T_g's in their DSC thermograms. These copolymers are presently being used as model materials to study fundamental parameters important for steric stabilization of dispersions in polar media. © 1993 John Wiley & Sons, Inc.     

Impact of Cationic Charge Density and PEGylated Poly(Amino Acid) Tercopolymer Architecture on Their Use as Gene Delivery Vehicles. Part 2: DNA Protection,Stability, Cytotoxicity,and Transfection Efficiency

The impact of the molecular architecture on the transfection efficiency of PEGylated poly(amino acid) block copolymers was investigated for PEG‐b‐p(l ‐Lys)_x‐b‐p(l ‐Leu)_y, PEG‐b‐p(l ‐Leu)_x‐b‐p(l ‐Lys)_y, and PEG‐b‐p((l ‐Leu)_x‐co‐(l ‐Lys)_y). The block lengths of p(l ‐Lys) and p(l ‐Leu) were varied between 10, 20, and 40; and 10 and 20, respectively, to study the influence of the ionic/hydrophobic balance. The results show that ABC triblock copolymers form smaller and more stable polyplexes with plasmid DNA than AB diblock copolymers—as verified by long‐term aggregation and ethidium bromide exclusion studies—protect the DNA more effectively against nucleases, and provide better transfection efficiencies, as indicated by total protein as well as luciferase expression. More detailed studies revealed that triblock copolymers with p(l ‐Leu) forming the C‐block were most efficient in DNA complexation with a 2.3 times higher transfection rate. Furthermore, increasing the cationic character by increasing the p(l ‐Lys) chain length led to up to 25% higher transfection but at the same time induced some cytotoxicity. Diblock copolymers, where the amino acid–building blocks exist as a random copolymer, bind more loosely with DNA leading to less compact and less stable aggregates with lower transfection efficiencies.     

Sorption of anionic amphiphilic block copolymers by a network polycation

The interaction of amphiphilic block copolymers comprising an anionic block (polyacrylate or polymethacrylate) and a hydrophobic block (polystyrene, poly(butyl acrylate) or polyisobutylene) with lightly crosslinked poly(N,N-diallyl-N,N-dimethylammonium chloride) is studied for the first time. It is shown that the cationic hydrogel can sorb anionic amphiphilic block copolymers via electrostatic interaction with the corona of block copolymer micelles. The rate of sorption of block copolymer polyelectrolytes is significantly lower than the rate of sorption of linear polyions and is controlled by the lengths of the hydrophilic and hydrophobic blocks and the flexibility of the latter blocks. The sorption of amphiphilic block copolymers is accompanied by their self-assembly in the polycomplex gel and formation of a continuous hydrophobic layer impermeable to water and the low-molecular-mass salt dissolved in it.     

SYNTHESIS AND CHARACTERIZATION OF WATER-SOLUBLE BLOCK COPOLYMERS WITH AN END-TAGGED NAPHTHALENE PROBE

Water-soluble A-B block copolymers of 2-perfluoroethyl-2-oxazoline or 2-pentyl-2-oxazoline as hydrophobic monomers and 2-methyl-2-oxazoline as hydrophilic monomer were prepared by means of the living cationic ring-opening polymerization. The polymerization was initiated with N-methyl-2-(1-naphthyl)-2-oxazolinium trifluoromethanesulfonate as fluorescence label followed by sequential addition of the hydrophobic and the hydrophilic monomer. The polymerization was monitored by ¹H NMR spectroscopy and gel permeation chromatography (GPC) measurements. The results revealed that fluorophilic block copolymers can be prepared by this method while lipohilic block copolymers are not accessible by this monomer sequence. Micelle formation of the fluorophilic block copolymers in aqueous solution was studied by means of steady-state fluorescence spectroscopy which confirmed strong intermolecular excimer formation of the terminal bounded naphthalene moiety. In chloroform as a good solvent for both blocks, only monomer fluorescence could be observed.     

Hollow nanoparticles prepared from pH‐responsive template polymer micelles

Water‐soluble crosslinked hollow nanoparticles were prepared using pH‐responsive anionic polymer micelles as templates. The template micelles were formed from pH‐responsive diblock copolymers (PAMPS‐PAaH) composed of the poly(sodium 2‐(acrylamido)‐2‐methylpropanesulfonate) and poly(6‐(acrylamido)hexanoic acid) blocks in an aqueous acidic solution. The PAMPS and PAaH blocks form a hydrophilic anionic shell and hydrophobic core of the core‐shell polymer micelle, respectively. A cationic diblock copolymer (PEG‐P(APTAC/CEA)) with the poly(ethylene glycol) block and random copolymer block composed of poly((3‐acrylamidopropyl)trimethylammonium chloride) containing a small amount of the 2‐(cinnamoyl)ethylacrylate photo‐crosslinkable unit can be adsorbed to the anionic shell of the template micelle due to electrostatic interaction, which form a core‐shell‐corona three‐layered micelle. The shell of the core‐shell‐corona micelle is formed from a polyion complex with anionic PAMPS and cationic P(APTAC/CEA) chains. The P(APTAC/CEA) chains in the shell of the core‐shell‐corona micelle can be photo‐crosslinked with UV irradiation. The template micelle can be dissociated using NaOH, because the PAaH blocks are ionized. Furthermore, electrostatic interactions between PAMPS and PAPTAC in the shell are screened by adding excess NaCl in water. The template micelles can be completely removed by dialysis against water containing NaOH and NaCl to prepare the crosslinked hollow nanoparticles. Transmission electron microscopy observations confirmed the hollow structure. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis of ABA‐triblock and star‐diblock copolymers with poly(2‐adamantyl vinyl ether) and poly(n‐butyl vinyl ether) segments: New thermoplastic elastomers composed solely of poly(vinyl ether) backbones

ABA‐type triblock copolymers and AB‐type star diblock copolymers with poly(2‐adamantyl vinyl ether) [poly(2‐AdVE)] hard outer segments and poly(n‐butyl vinyl ether) [poly(NBVE)] soft inner segments were synthesized by sequential living cationic copolymerization. Although both the two polymer segments were composed solely of poly(vinyl ether) backbones and hydrocarbon side chains, they were segregated into microphase‐separated structure, so that the block copolymers formed thermoplastic elastomers. Both the ABA‐type triblock copolymers and the AB‐type star diblock copolymers exhibited rubber elasticity over wide temperature range. For example, the ABA‐type triblock copolymers showed rubber elasticity from about ?53 °C to about 165 °C and the AB‐type star diblock copolymer did from about ?47 °C to 183 °C with a similar composition of poly(2‐AdVE) and poly(NBVE) segments in the dynamic mechanical analysis. The AB‐type star diblock copolymers exhibited higher tensile strength and elongation at break than the ABA‐type triblock copolymers. The thermal decomposition temperatures of both the block copolymers were as high as 321–331 °C, indicating their high thermal stability. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Aggregate morphologies of amphiphilic ABC triblock copolymer in dilute solution using self-consistent field theory

The complex microstructures of amphiphilic ABC linear triblock copolymers in which one of the end blocks is relatively short and hydrophilic, and the other two blocks B and C are hydrophobic in a dilute solution, have been investigated by the real-space implementation of self-consistent field theory (SCFT) in two dimensions (2D). In contrast to diblock copolymers in solution, the aggregation of triblock copolymers are more complicated due to the presence of the second hydrophobic blocks and, hence, big ranges of parameter space controlling the morphology. By tailoring the hydrophobic degree and its difference between the blocks B and C, the various shapes of vesicles, circlelike and linelike micelles possibly corresponding to spherelike, and rodlike micelles in 3D, and especially, peanutlike micelles not found in diblock copolymers are observed. The transition from vesicles to circlelike micelles occurs with increasing the hydrophobicity of the blocks B and C, while the transition from circlelike micelles to linelike micelles or from the mixture of micelles and vesicles to the long linelike micelles takes place when the repulsive interaction of the end hydrophobic block C is stronger than that of the middle hydrophobic block B. Furthermore, it is favorable for dispersion of the block copolymer in the solvent into aggregates when the repulsion of the solvent to the end hydrophobic block is larger than that of the solvent to the middle hydrophobic block. Especially when the bulk block copolymers are in a weak segregation regime, the competition between the microphase separation and macrophase separation exists and the large compound micelle-like aggregates are found due to the macrophase separation with increasing the hydrophobic degree of blocks B and C, which is absent in diblock copolymer solution. The simulation results successfully reproduce the existing experimental ones.     

Biocompatible poly(ethylene glycol)‐poly(γ‐cholesterol‐L‐glutamate) copolymers: Synthesis,characterization, and in vitro studies

A novel amphiphilic poly(ethylene glycol)‐block‐poly(γ‐cholesterol‐L ‐glutamate) (mPEG–PCHLG) diblock copolymer has been synthesized. The mPEG–PCHLG copolymer has good biocompatibility and low toxicity. The mPEG–PCHLG copolymers could aggregate into nanoparticles with PCHLG blocks as the hydrophobic core and PEG blocks as the hydrophilic shell through emulsion solvent evaporation method. The copolymers were characterized by nuclear magnetic resonance spectroscopy, mass spectrum, Fourier transform infrared spectroscopy, and gel permeation chromatography. The particle sizes, size distributions, and zeta potentials of nanoparticles can also be determined by dynamic light scattering and transmission electron microscopy. This work provides a new and facile approach to prepare amphiphilic block copolymer nanoparticles with controllable performances. This novel copolymer may have potential applications in drug delivery and bioimaging applications.© 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Preparation and aggregation behavior of mannose-terminated poly(ethylene glycol)-b-poly(L-leucine) in water

Amphiphilic diblock copolymers composed of poly(ethylene glycol) (PEG) and poly(l-leucine) (PLeu) with mannose at the chain end of PEG were synthesized by a combination of ring-opening polymerization (ROP) and click chemistry. First, an α-azido, ω-amino PEG (N(3)-PEG-NH(2)) was synthesized and converted to the corresponding amine hydrochloride (N(3)-PEG-NH(2)·HCl), which was used as a macroinitiator to initiate the ROP of L-leucine-N-carboxyanhydride (Leu-NCA), yielding three amphiphilic block copolymers with different chain lengths of PLeu (N(3)-PEG-b-PLeu). Then, click chemistry of the alkynyl mannose with N(3)-PEG-b-PLeu anchored a mannose moiety to the PEG chain end of the copolymer. The self-assembly behavior of these copolymers in water was investigated using transmission electron microscopy (TEM), laser light scattering (LLS) and circular dichroism (CD). Depending on the copolymer composition and the initial concentration of the copolymer in organic solvent, different morphologies (e.g. spherical micelle, wormlike micelle) were observed. The aggregation behavior was demonstrated to be controlled by secondary structure formation and the hydrophobic interactions of the PLeu segments. With mannose moieties on the surface of the aggregates, these aggregates could bind reversibly the lectin Concanavalin A (Con A).     

Computer simulation of architectural and molecular weight effects on the assembly of amphiphilic linear-dendritic block copolymers in solution

Langevin dynamics simulations are performed on linear-dendritic diblock copolymers containing bead-spring, freely jointed chains composed of hydrophobic linear monomers and hydrophilic dendritic monomers. The critical micelle concentration (CMC), micelle size distribution, and shape are examined as a function of dendron generation and architecture. For diblock copolymers with a linear block of fixed length, it is found that the CMC increases with increasing dendron generation. This trend qualitatively agrees with experiments on linear-dendritic diblock and triblock copolymers with hydrophilic dendritic blocks and hydrophobic linear blocks. The flexibility of the dendritic block is altered by varying the number of spacer monomers between branch points in the dendron. When comparing linear-dendritic diblock copolymers with similar molecular weights, it is shown that increasing the number of spacer monomers in the dendron lowers the CMC due to an increase in flexibility of the dendritic block. Analysis on the micellar structure shows that linear-dendritic diblock copolymers pack more densely than what would be expected for a linear-linear diblock copolymer of the same molecular weight.     

Double-Gyroid Network Morphology in Tapered Diblock Copolymers

We report the formation of a double-gyroid network morphology in normal-tapered poly(isoprene-b-isoprene/styrene-b-styrene) [P(I-IS-S)] and inverse-tapered poly(isoprene-b- styrene/isoprene-b-styrene) [P(I-SI-S)] diblock copolymers. Our tapered diblock copolymers with overall poly(styrene) volume fractions of 0.65 (normal-tapered) and 0.67 (inverse-tapered), and tapered regions comprising 30 volume percent of the total polymer, were shown to self-assemble into the double-gyroid network morphology through a combination of small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM). The block copolymers were synthesized by anionic polymerization, where the tapered region between the pure poly(isoprene) and poly(styrene) blocks was generated using a semi-batch feed with programmed syringe pumps. The overall composition of these tapered copolymers lies within the expected network-forming region for conventional poly(isoprene-b-styrene) [P(I-S)] diblock copolymers. Dynamic mechanical analysis (DMA) clearly demonstrated that the order-disorder transition temperatures (T(ODT)'s) of the network-forming tapered block copolymers were depressed when compared to the T(ODT) of their non-tapered counterpart, with the P(I-SI-S) showing the greater drop in T(ODT). These results indicate that it is possible to manipulate the copolymer composition profile between blocks in a diblock copolymer, allowing significant control over the T(ODT), while maintaining the ability to form complex network structures.     

Synthesis of Poly(Styrene)-block-poly(methacrylate)-block-poly(styrene) via Site Transformation Reaction

Abstract

Triblock copolymers with polystyrene outer blocks and an inner polymethacrylate block were synthesized by a site transformation reaction using anionic and cationic polymerization techniques. In order to obtain such ABA block copolymers, two synthetic routes have been applied. In the first case, different methacrylates (methyl methacrylate, 2-ethylhexyl methacrylate) were polymerized anionically with a bifunctional initiator to get poly(methacrylate) dianions later forming the inner block whereas in the second case poly(styrene)-block-poly(methacrylate) anions were synthesized by monofunctional initiation via sequential monomer addition. In a subsequent step, the living chain ends of the methacrylate dianions on one side, and the diblock copolymer anions on the other side, were functionalized with 1,4-bis(l-bromoethyl)benzene in order to obtain a potential bifunctional or monofunctional macroinitiator for the cationic polymerization of styrene. Then, styrene was polymerized cationically with the macroinitiator in the presence of SnCl₄ as coinitiator and _n Bu₄NBr as a common ion salt in CH₂Cl₂ at -15°C. Block formation was proven by SEC measurements, preparative SEC and NMR characterization.     

Behavior of a Thermosensitive Star-Shaped Polymer with Polyethyloxazoline-<Emphasis Type="Italic">block</Emphasis>-Polyisopropyloxazoline Copolymer Arms

The aqueous solutions of the star-shaped eight-arm polymer in which arms consist of the block copolymer of poly(2-ethyl-2-oxazoline) and poly(2-isopropyl-2-oxazoline) and a more hydrophilic poly(2- ethyl-2-oxazoline) is attached to the calix[8]arene core are studied by light scattering and turbidimetry. For the sake of comparison, the linear block copolymer modeling arms of the star-shaped polymer is examined. The temperature and concentration dependences of light scattering intensity and optical transmission, the hydrodynamic radii of particles occurring in solutions, and their fraction in solution are determined. At room temperature, solutions of the linear copolymer are molecularly dispersed because of a high hydrophilicity of blocks and aggregates are formed in solutions of the star-shaped polymer as a result of interaction between hydrophobic calix[8]arene cores. As the temperature grows, the dehydration of poly(2-isopropyl-2-oxazoline) units initially occurs and entails both the compaction and aggregation of star-shaped molecules. At higher temperatures, the dehydration of poly(2-ethyl-2-oxazoline) leading to phase separation begins. The temperature of phase separation grows upon dilution. A high intramolecular density of the star-shaped polymer is responsible for a marked deceleration of self-organization processes. This effect is especially pronounced in the vicinity of the phase-separation temperature.