PEG Block Length Research Articles

PH-Responsive Poly(ethylene glycol)-b-poly(2-vinylpyridine) Micelles for the Triggered Release of Therapeutics

The use of pH-responsive polymeric micelles is a promising approach to afford the targeted, pH-mediated delivery of hydrophobic drugs within the low-pH tumour milieu and intracellular organelles of cancer cells. However, even for a common pH-responsive polymeric micelle system-e.g., those utilising poly(ethylene glycol)-b-poly(2-vinylpyridine) (PEG-b-PVP) diblock copolymers-there is a lack of available data describing the compatibility of hydrophobic drugs, as well as the relationships between copolymer microstructure and drug compatibility. Furthermore, synthesis of the constituent pH-responsive copolymers generally requires complex temperature control or degassing procedures that limit their accessibility. Herein we report the facile synthesis of a series of diblock copolymers via visible-light-mediated photocontrolled reversible addition-fragmentation chain-transfer polymerisation, with a constant PEG block length (90 repeat units (RUs)) and varying PVP block lengths (46-235 RUs). All copolymers exhibited narrow dispersity values (Đ ≤ 1.23) and formed polymeric micelles with low polydispersity index (PDI) values (typically <0.20) at physiological pH (7.4), within a suitable size range for passive tumour targeting (<130 nm). The encapsulation and release of three hydrophobic drugs (cyclin-dependent kinase inhibitor (CDKI)-73, gossypol, and doxorubicin) were investigated in vitro at pH 7.4-4.5 to simulate drug release within the tumour milieu and cancer cell endosome. Marked differences in drug encapsulation and release were observed when the PVP block length was increased from 86 to 235 RUs. With a PVP block length of 235 RUs, the micelles exhibited differing encapsulation and release properties for each drug. Minimal release was observed for doxorubicin (10%, pH 4.5) and CDKI-73 exhibited moderate release (77%, pH 4.5), whereas gossypol exhibited the best combination of encapsulation efficiency (83%) and release (91% pH 4.5) overall. These data demonstrate the drug selectivity of the PVP core, where both the block molecular weight and hydrophobicity of the core (and accordingly the hydrophobicity of the drug) have a significant effect on drug encapsulation and release. These systems remain a promising means of achieving targeted, pH-responsive drug delivery-albeit for select, compatible hydrophobic drugs-which warrants their further investigation to develop and evaluate clinically relevant micelle systems.

Interrogating the relationship between the microstructure of amphiphilic poly(ethylene glycol-b-caprolactone) copolymers and their colloidal assemblies using non-interfering techniques

Understanding the microstructural parameters of amphiphilic copolymers that control the formation and structure of aggregated colloids (e.g., micelles) is essential for the rational design of hierarchically structured systems for applications in nanomedicine, personal care and food formulations. Although many analytical techniques have been employed to study such systems, in this investigation we adopted an integrated approach using non-interfering techniques – diffusion nuclear magnetic resonance (NMR) spectroscopy, dynamic light scattering (DLS) and synchrotron small-angle X-ray scattering (SAXS) – to probe the relationship between the microstructure of poly(ethylene glycol-b-caprolactone) (PEG-b-PCL) copolymers [e.g., block molecular weight (MW) and the mass fraction of PCL (fPCL)] and the structure of their aggregates. Systematic trends in the self-assembly behaviour were determined using a large family of well-defined block copolymers with variable PEG and PCL block lengths (number-average molecular weights (Mn) between 2 and 10 and 0.5–15 kDa, respectively) and narrow dispersity (Ð < 1.12). For all of the copolymers, a clear transition in the aggregate structure was observed when the hydrophobic fPCL was increased at a constant PEG block Mn, although the nature of this transition is also dependent on the PEG block Mn. Copolymers with low Mn PEG blocks (2 kDa) were observed to transition from unimers and loosely associated unimers to metastable aggregates and finally, to cylindrical micelles as the fPCL was increased. In comparison, copolymers with PEG block Mn of between 5 and 10 kDa transitioned from heterogenous metastable aggregates to cylindrical micelles and finally, well-defined ellipsoidal micelles (of decreasing aspect ratios) as the fPCL was increased. In all cases, the diffusion NMR spectroscopy, DLS and synchrotron SAXS results provided complementary information and the grounds for a phase diagram relating copolymer microstructure to aggregation behaviour and structure. Importantly, the absence of commonly depicted spherical micelles has implications for applications where properties may be governed by shape, such as, cellular uptake of nanomedicine formulations.

Size and Shape Control of Ice Crystals by Amphiphilic Block Copolymers and Their Implication in the Cryoprotection of Mesenchymal Stem Cells.

Precise control over the size and shape of ice crystals is a key factor to consider in designing antifreezing and cryoprotecting molecules for cryopreservation of cells. Here, we report that a poly(ethylene glycol)-poly(l-alanine) (PEG-PA) block copolymer exhibits excellent cryoprotecting properties for stem cells and antifreezing properties for water. As the molecular weight of PA increased from 500, 760, and 1750 Da (P1, P2, and P3) at the same PEG molecular weight of 5000 Da, the β-sheet content decreased and α-helix content increased. Comparing P2 (PEG-PA; 5000-760) and P4 (PEG-PA: 1000-750), β-sheets increased as the PEG block length decreased. The critical micelle concentration of the PEG-PA block copolymers was in a range of 0.5-3.0 mg/mL and was proportional to the hydrophobicity of the PEG-PA block copolymers. The P1, P2, and P3 self-assembled into spherical micelles, whereas P4 formed micelles with cylindrical morphology. The difference in the block copolymer structure affected ice recrystallization inhibition (IRI) activity and cryopreservation of cells. IRI activity was assayed via mean largest grain size (MLGS), and interactions between polymers and ice crystal surfaces were studied by dynamic ice-shaping studies. The MLGS decreased to 58 → 53 → 45 → 35 → 23% of that of PBS, as the polymer (PEG-PA 5000-500) concentration increased from 0.0 (PBS; control) → 1.0 → 5.0 → 10 → 30 → 50 mg/mL. The MLGS of PEG 5k solutions (negative control) decreased to 74 → 71 → 64 → 44 → 37% of that of PBS in the same concentration range. P3 and P4 with a longer hydrophobic PA block developed elongated ice crystals at above 30 mg/mL. The dynamic ice-shaping study exhibited that ice crystals became needle-shaped, as the hydrophobicity of the polymer increased as in P2-P4. The cell recovery in the P1 system after cryopreservation at -196 °C for 7 days was 87% of that of the dimethyl sulfoxide (DMSO) 10% system (positive control). The cell recovery was 48% for the P2 system and drastically decreased to less than 30% of that of the DMSO 10% system in the P3, P4, PEG 5k, PEG 1k, PVA 80H, and PVA 100H systems. Current studies suggest that IRI activity, round ice crystal shaping, and membrane stabilization activity of P1 cooperatively provide excellent cell recovery among the candidate systems. Recovered stem cells exhibited excellent proliferation and multilineage differentiation into osteocytes, chondrocytes, and adipocytes. To conclude, the PEG-PA (5000-500) block copolymer is suggested to be a promising antifreezing cryoprotectant for stem cells.

Self-assembly, pH-responsibility and controlled release of doxorubicin of PDEAEMA-PEG-PDEAEMA triblock copolymers: effects of PEG length

Effects of poly(ethylene glycol) (PEG) block length on the self-assembly of a series of pH-sensitive poly(N,N-diethylaminoethyl methacrylate)m-PEGn-poly(N,N-diethylaminoethyl methacrylate)m triblock copolymers (PDEAEMAm-PEGn-PDEAEMAm) have been studied. The synthesized triblock copolymers have an almost fixed PDEAEMA block length (m ≈ 65) and varying PEG block lengths (n = 11, 20, 89 or 134). The acid–base titration results show that the pKa value of the block copolymer shifts from 6.84 to 7.08 when the PEG block length increases from 11 to 134, indicating that the pH-sensitivity of the triblock copolymer can be adjusted through changing the PEG block length. With the increase of the hydrophilic PEG block length, the critical micelle concentration value of the triblock copolymer obtained from fluorescence spectroscopy changes from 5.50 × 10–3 to 13.23 × 10–3 mg mL−1. The block copolymers can self-assemble into the micelles in PBS solution at pH 7.4, and the average size of the self-assembly decreases from 178 nm to 45 nm with the increase of the PEG block length as determined by dynamic light scattering. The block copolymers show great biocompatibility in the cytotoxicity assay. Results from these triblock copolymers in the drug-controlled release indicate that the release rate of doxorubicin-loaded micelles at pH 5.0 is faster than that at pH 7.4, and the cumulative drug release in 48 h at pH 5.0 increases from 70.4% to 89.8% with the decrease of the PEG block length. Accordingly, this PDEAEMA65-PEGn-PDEAEMA65 copolymer is an excellent carrier for controllable drug delivery and release.

The effect of PCL/PEG ABA block lengths on the crystallization of homo/block- based polyurethane/CNW nanocomposites

We report synthesis and characterization of a set of thermoset polyurethane (PU) bionanocomposites based on a polyol blend of poly(e-caprolactone)/ polyethylene glycol (PCL/PEG) ABA block copolymers and their homopolymers (Mw: 2000 D). ABA block copolymers of PCL/PEG, with variable block lengths, were blended with their homopolymers. The relative weight content of Homo: Block (HB) was set 1:1 and the blend was used to synthesize a PU bionanocomposite using HDI and cellulose nanowhisker (CNW). The change in PEG and PCL block lengths resulted in an extensive change in the crystallization of the soft domains. The results of dynamic and thermal analysis revealed an increasing trend in the crystallization of the PCL/PEG segments as their lengths increase in the block copolymer structure. The shape memory analysis of the PU specimens showed high recovery (84-100%) and fixity (93-100%) ratios. Specimens with about one-order of magnitude fall in the storage modulus in the plateau region showed the highest fixity ratios. The relatively stable storage modulus at the elevated temperature indicate lack of flow for the PU nanocomposites and their thermoset nature. The cytotoxity analysis of the specimens showed a great cytocompatibility, indicating their great potential in the field of tissue engineering as a new biomaterial model. HB6 was selected as the optimum sample with SR and SF of 100%, with the highest cell viability.

Bioresorbable hydrogels prepared by photo-initiated crosslinking of diacrylated PTMC-PEG-PTMC triblock copolymers as potential carrier of antitumor drugs

PTMC-PEG-PTMC triblock copolymers were prepared by ring-opening polymerization of trimethylene carbonate (TMC) in the presence of dihydroxylated poly(ethylene glycol) (PEG) with Mn of 6000 and 10,000 as macro-initiator. The copolymers with different PTMC block Lengths and the two PEGs were end functionalized with acryloyl chloride. The resulting diacrylated PEG-PTMC-DA and PEG-DA were characterized by using NMR, GPC and DSC. The degree of substitution of end groups varied from 50.0 to 65.1%. Hydrogels were prepared by photo-crosslinking PEG-PTMC-DA and PEG-DA in aqueous solution using a water soluble photo-initiator under visible light irradiation. The effects of PTMC and PEG block lengths and degree of substitution on the swelling and weight loss of hydrogels were determined. Higher degree of substitution leads to higher crosslinking density, and thus to lower degree of swelling and weight loss. Similarly, higher PTMC block length also leads to lower degree of swelling and weight loss. Freeze dried hydrogels exhibit a highly porous structure with pore sizes from 20 to 100 µm.The biocompatibility of hydrogels was evaluated by MTT assay, hemolysis test, and dynamic clotting time measurements. Results show that the various hydrogels present outstanding cyto- and hemo-compatibility. Doxorubicin was taken as a model drug to evaluate the potential of PEG-PTMC-DA and PEG-DA hydrogels as drug carrier. An initial burst release was observed in all cases, followed by slower release up to more than 90%. The release rate is strongly dependent on the degree of swelling. The higher the degree of swelling, the faster the release rate. Finally, the effect of drug loaded hydrogels on SKBR-3 tumor cells was evaluated in comparison with free drug. Similar cyto-toxicity was obtained for drug loaded hydrogels and free drug at comparable drug concentrations. Therefore, injectable PEG-PTMC-DA hydrogels with outstanding biocompatibility and drug release properties could be most promising as bioresorbable carrier of hydrophilic drugs.

Effects of soft segment characteristics on the properties of biodegradable amphiphilic waterborne polyurethane prepared by a green process

Traditional 3D printing materials are not suitable for tissue engineering due to their toxicity, low degradability and poor biocompatibility. In this study, a new amphiphilic biodegradable waterborne polyurethane (WBPU) was developed by a green and sustainable process without any organic solvents, catalysts or cross-linkers. The soft segments of this kind of WBPU were formed by replacing hydrophobic poly(e-caprolactone) diol with hydrophilic poly(ethylene glycol) (PEG). Different block lengths of PEG were used for this purpose. The combination of ester and ether groups endowed WBPU with amphiphilic characteristics, which is important for regeneration and maintenance of tissue. The effects of composition and content of soft segments on the phase separation, thermal properties, mechanical properties, water absorption, biodegradability and cytotoxicity of WBPU were investigated. The results showed that the desired properties of WBPU could be achieved by tuning the block length of PEG and content of soft segments. The present work provided a new approach to prepare WBPUs with amphiphilic and biodegradable characteristics, which are promising candidates for 3D printing materials for tissue engineering scaffolds.

Effect of drug loading on the properties of temperature‐responsive polyester–poly(ethylene glycol)–polyester hydrogels

AbstractHydrogels that can undergo gelation upon injection in vivo are promising systems for the site‐specific delivery of drugs. In particular, some thermo‐responsive gels require no chemical additives but simply gel in response to a change from a lower temperature to physiological temperature (37 °C). The gelation mechanism does not involve covalent bonds, and it is possible that incorporation of drugs into the hydrogel could disrupt gelation. We investigated the incorporation of drugs into thermo‐responsive hydrogels based on poly(ϵ‐caprolactone‐co‐lactide)‐block‐poly(ethylene glycol)‐block‐poly(ϵ‐caprolactone‐co‐lactide) (PCLA–PEG–PCLA). Significant differences in properties and in the response to incorporation of the anti‐inflammatory drug celecoxib (CXB) were observed as the PEG block length was varied from 1500 to 3000 g mol−1. Linear viscoelastic moduli of a PCLA–PEG–PCLA hydrogel containing a 2000 g mol−1 PEG block were least affected by the incorporation of CXB and this gel also exhibited the slowest release of CXB, so the incorporation of phenylbutazone, methotrexate, ibuprofen, diclofenac and etodolac was also investigated for this hydrogel. Different drugs resulted in varying degrees of syneresis of the hydrogels, suggesting that they interact with the polymer networks in different ways. In addition, the drugs had varying effects on the viscoelastic and compressive moduli of the gels. The results showed that the effects of drug loading on the properties of thermo‐responsive hydrogels can be substantial and depend on the drug. For applications such as intra‐articular drug delivery, in which the mechanical properties of the hydrogel are important, these effects should thus be studied on a case‐by‐case basis. © 2019 Society of Chemical Industry

Thermal and mechanical properties of highly flexible poly(L-lactide)-b-poly(ethylene glycol)-b-poly(L-lactide) bioplastics: Effects of poly(ethylene glycol) block length and chain extender

The brittleness of poly(L-lactide) (PLLA) bioplastic is the main disadvantage for practical applications. Herein, we report the synthesis of high-molecular-weight PLLA- b-poly(ethylene glycol)- b-PLLA (PLLA-PEG-PLLA) block copolymers by ring-opening polymerization of LLA. The highly flexible PLLA-PEG-PLLAs were prepared by reactive melt blending with an epoxy-based chain extender formed as long-chain branched structures. The effects of PEG block length and content of chain extender were investigated. The results showed that the chain extension reaction reduced crystallinities of the PLLA-PEG-PLLAs. All the chain-extended PLLA-PEG-PLLA films had no phase separation. The lower crystallinities of PLLA-PEG-PLLA films obtained with higher contents of chain extender enhanced the film drawability. The longer PEG block length resulted in higher strain at break and lower stress at the break of PLLA-PEG-PLLA films. These chain-extended PLLA-PEG-PLLAs have potential for use as highly flexible bioplastics.

Synthesis and 3D Printing of PEG-Poly(propylene fumarate) Diblock and Triblock Copolymer Hydrogels.

PEG-based hydrogels are used widely in exploratory tissue engineering applications but in general lack chemical and structural diversity. Additive manufacturing offers pathways to otherwise unattainable scaffold morphologies but has been applied sparingly to cross-linked hydrogels. Herein, mono methyl ether poly(ethylene glycol) (PEG) and PEG-diol were used to initiate the ring-opening copolymerization (ROCOP) of maleic anhydride and propylene oxide to yield well defined diblock and triblock copolymers of PEG-poly(propylene maleate) (PPM) and ultimately poly(propylene fumarate) (PPF) with different molecular mass PEG macroinitiators and block length ratios. Using continuous digital light processing (cDLP) hydrogels were photochemically printed from an aqueous solution which resulted in a 10-fold increase in elongation at break compared to traditional diethyl fumarate (DEF) based printing. Furthermore, PPF-PEG-PPF triblock hydrogels were also found to be biocompatible in vitro across a number of engineered MC3T3, NIH3T3, and primary Schwann cells.

Synthesis and self-assembly of stearic acid-poly (ethylene glycol) block copolymer

Stearic acid-poly(ethylene glycol) (STA-PEG) block copolymers with different hydrophilic segment length were successfully synthesized by the mild esterification. And self-assembly behaviour of the STA-PEGwas followed by fluorescence spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM). The results show that the sphere micelles are formed with the STA block as the core and PEG block as the shell in aqueous solution. In addition, with the increase of PEG block length, the diameters of micelles increase from 148nm to 228nm, and the critical micelle concentration (CMC) decreased from 0.0013mg/ml to 0.0004mg/ml. The very low CMC value indicated that the STA-b-PEG can self-assemble into micelles easily and the formed micelles were stable in very dilute solution

Influence of Composition of Amphiphilic Double-Crystalline P3HT-b-PEG Block Copolymers on Structure Formation in Aqueous Solution

A series of poly(3-hexylthiophene)-block-poly(ethylene glycol) (P3HT-b-PEG) with constant P3HT block length block and variable PEG block lengths are presented. Alkyne-functionalized P3HT with high absolute molecular weight of 11.4 kg/mol is combined with azide-functionalized PEGs via copper-catalyzed alkyne–azide cycloaddition (CuAAC). The resulting P3HT-b-PEG block copolymers have PEG weight fractions between 15 and 64 wt %. In bulk materials the crystallinity in the conjugated block is similar to pure P3HT, while the crystallinity of PEG is influenced with decreasing PEG block length. On addition of MeOH as a nonsolvent for the P3HT block, these block copolymers are able to form stable micellar aggregates if the PEG fraction is >31 wt %. In AFM, DLS, and cryo-TEM, P3HT-b-PEG micelles are found to have a spherical or cylindrical shape with diameters of around 25 nm and lengths between 40 nm and some hundred nanometers. It is found that short PEG blocks lead to bigger block copolymer micelles. Thus, a cor...

Synthesis and characterization of biodegradable copoly(ether-ester-urethane)s and their chitin whisker nanocomposites

A series of copoly(ether-ester-urethane)s have been synthesized from poly(3-hydroxybutyrate) (PHB) diol prepolymer, as hard segments, and copoly(e-caprolactone-ethylene glycol-e-caprolactone) (PCL-PEG-PCL) diols with different PEG block lengths, as soft segments, with/without chitin whiskers (ChW) using hexamethylene diisocyanate, as a coupling agent, in one-step polymerization. The PHB content in the resulting copolymers was 0 and 40 %, and the content of ChW was varied from 0 to 5 %. The chemical structure of the resulting copolymers was characterized by FTIR, 1H-NMR and 13C-NMR spectra. The effect of chemical structure and ChW content on the thermal properties was studied by differential scanning calorimetry (DSC) and thermogravimetric analysis (TG). The DSC data revealed that the ΔH m of both PHB and PCL-PEG-PCL slightly increases with increasing the ChW content. The cold and melt crystallization of PHB enhanced with increasing ChW content. The TG data revealed that the thermal stability of copolymers slightly enhanced at high content of ChW. The swelling behavior of the copolymers was also investigated.

Specific Drug Formulation Additives: Revealing the Impact of Architecture and Block Length Ratio.

Combining poly(ethylene glycol) (PEG) with sequence-defined peptides in PEG-peptide conjugates offers opportunities to realize next-generation drug formulation additives for overcoming undesired pharmacological profiles of difficult small molecule drugs. The tailored peptide segments provide sequence-specific, noncovalent drug binding, and the hydrophilic PEG block renders the complexes water soluble. On the basis of a peptide sequence known to bind the photosensitizer m-tetra(hydroxyphenyl)chlorin (m-THPC) for photodynamic cancer therapy, a set of different conjugate architectures is synthesized and studied. Variations in PEG block length and amplification of the peptidic binding domain of PEG-peptide conjugates are used to fine tune critical parameters for hosting m-THPC, such as drug payload capacities, aggregation sizes, and drug release and activation kinetics.

Posters

Self-healing functional polymer surfaces, designed with an intrinsic and spontaneous mechanism which replenishes the damaged surfaces with the original chemical functionalities, are of great interest to maintain a high performance of the functionality and extend the life-time of materials.We report self-replenishing UV-cured hydrophobic polymer films prepared through the incorporation of methacrylate-terminated perfluorinated-dangling chains into poly(ethylene glycol diacrylate) (PEGDA)-based networks. The films are able to spontaneously and fully self-replenish the surface hydrophobicity, multiple times, upon consecutive intentional damages. The rate of recovery was found to be dependent on the glass transition temperature (Tg) of the networks, which directly correlates to the PEG block length in the PEGDA oligomer used. This study demonstrates that an intrinsic self-replenishing mechanism can be implemented in new network architectures, created rapidly and efficiently by free radical UV-polymerization, which allows preparing self-healing functional polymer films in a faster and eco-friendlier way.

UV-cured self-replenishing hydrophobic polymer films

Self-healing functional polymer surfaces, designed with an intrinsic and spontaneous mechanism which replenishes the damaged surfaces with the original chemical functionalities, are of great interest to maintain a high performance of the functionality and extend the life-time of materials.We report self-replenishing UV-cured hydrophobic polymer films prepared through the incorporation of methacrylate-terminated perfluorinated-dangling chains into poly(ethylene glycol diacrylate) (PEGDA)-based networks. The films are able to spontaneously and fully self-replenish the surface hydrophobicity, multiple times, upon consecutive intentional damages. The rate of recovery was found to be dependent on the glass transition temperature (Tg) of the networks, which directly correlates to the PEG block length in the PEGDA oligomer used. This study demonstrates that an intrinsic self-replenishing mechanism can be implemented in new network architectures, created rapidly and efficiently by free radical UV-polymerization, which allows preparing self-healing functional polymer films in a faster and eco-friendlier way.

FT-IR characterization and hydrolysis of PLA-PEG-PLA based copolyester hydrogels with short PLA segments and a cytocompatibility study

A series of the biodegradable copolyester hydrogels was prepared using a redox-initiated polymerization with a constant 1:9 mole ratio of the Boltorn-based acrylate and diacrylate triblock comacromonomers. The Boltorn (R) macromonomer was derived from the hyperbranched polyester Boltorn H20, which was functionalized at each terminus with poly(ethylene glycol) acrylate, and the diacrylate triblock macromonomer was poly (lactide-b-ethylene glycol-b-lactide) diacrylate. The hydrolysis of the copolyesters at pH 7.4 in a phosphate buffered saline solution at 37 degrees C was studied using ATR-FTIR spectroscopy. It was found that the presence of the Boltorn, the PEG, and lactide block lengths both play vital roles in determining the structure-property relationships in these materials. The ATR-FTIR studies showed that with increasing lactide segment length, the rate of ester hydrolysis increased due to the increased concentration of the hydrolytically sensitive poly(lactic acid) (PLA) ester groups in the network. However, incorporation of Boltorn into the PLA-PEG-PLA copolymer did not significantly change the kinetic rate constant for hydrolysis of the PLA segments. The cytocompatibility of a typical one of these materials in the presence of its degradation by-products was assessed using cultured osteoblasts from the rat. The hydrogel was degraded for 28 days and found to be cytocompatible with osteoblasts over days 23 to 28 of the hydrolysis period. (c) 2013 Wiley Periodicals, Inc.

Click cyclization of linear triblock copolymers at block junctions under high concentration due to end-block shielding

Linear triblock copolymers of poly(N-isopropylacrylamide) (PNIPAM) and poly(ethylene glycol) (PEG) with two azide groups at both block junctions (PNIPAM-N3-PEG-N3-PNIPAM) are click reacted with dipropargyl oxalylate under high polymer concentration (250 g/L). Benefiting from rapid feature of alkyne-azide click reaction and spatial shielding of PNIPAM end blocks, PEG center block of PNIPAM-N3-PEG-N3-PNIPAM remains separated although PNIPAM end blocks keep in contact under this high concentration. Therefore, PNIPAM-N3-PEG-N3-PNIPAM undergoes self-cyclization at block junctions to form tadpole-shaped architecture while N3-PEG-N3 without PNIPAM end blocks inter-connects linearly. The influence of block lengths of PEG and PNIPAM on the unusual cyclization under high polymer concentration is studied.

Multicompartmental Hollow Micelles Formed by Linear ABC Triblock Copolymers in Aqueous Medium

Self-assembly behavior of an ABC triblock copolymer, poly(ethylene glycol)-b-polystyrene-b-poly(ε-caprolactone) (PEG-b-PS-b-PCL), in aqueous media is presented. The formed micelle structures were analyzed by using transmission electron microscopy, scanning electron microscopy, and laser light scattering. Various fascinating multicompartmental aggregates, including multilamellar vesicles, cylinder-containing vesicles, entrapped vesicles, and porous large compound micelles, were prepared from four copolymers with various block lengths of PEG and PS. The phase separation of hydrophobic PS and PCL blocks, as well as the hydrophilic/hydrophobic balance, plays a crucial role on the self-assembly behaviors. The mechanism regarding the formation of these fascinating aggregates is also suggested.

Controlled Thermoresponsive Hydrogels by Stereocomplexed PLA-PEG-PLA Prepared via Hybrid Micelles of Pre-Mixed Copolymers with Different PEG Lengths

The stereocomplexed hydrogels derived from the micelle mixture of two enantiomeric triblock copolymers, PLLA-PEG-PLLA and PDLA-PEG-PDLA, reported in 2001 exhibited sol-to-gel transition at approximately body temperature upon heating. However, the showed poor storage modulus (ca. 1000 Pa) determined their insufficiency as injectable implant biomaterials for many applications. In this study, the mechanical property of these hydrogels was significantly improved by the modifications of molecular weights and micelle structure. Co-micelles composed of block copolymers with two sizes of PEG block length were shown to possess unique and dissimilar properties from the micelles composed of single-sized block copolymers. The stereomixture of PLA-PEG-PLA comicelles showed a controllable sol-to-gel transition at a wide temperature range of 4 and 80 °C. The sol-gel phase diagram displays a linear relationship of temperature versus copolymer composition; hence, a transition at body temperature can be readily achieved by adjusting the mixed copolymer ratio. The resulting thermoresponsive hydrogels exhibit a storage modulus notably higher (ca. 6000 Pa) than that of previously reported hydrogels. As a physical network solely governed by self-reorganization of micelles, followed by stereocomplexation, this unique system offers practical, safe, and simple implantable biomaterials.