PEG Triblock Copolymers Research Articles

Blood Protein Exclusion from Polymer Brushes.

We report interactions between adsorbed copolymers of poly(ethylene glycol) (PEG) in the presence of two abundant blood proteins, serum albumin and an immunoglobulin G, up to physiological blood concentrations. We directly and nonintrusively measure interactions between PEG triblock copolymers (PEG-PPO-PEG) adsorbed to hydrophobic colloids and surfaces using Total Internal Reflection Microscopy, which provides kT- and nanometer-scale resolution of interaction potentials (energy vs separation). In the absence of protein, adsorbed PEG copolymer repulsion is consistent with dimensions and architectures of PEG brushes on both colloids and surfaces. In the presence of proteins, we observe concentration dependent depletion attraction and no change to brush repulsion, indicating protein exclusion from PEG brushes. Because positive and negative protein adsorption are mutually exclusive, our observations of concentration dependent depletion attraction with no change to brush repulsion unambiguously indicate the absence of protein coronas at physiological protein concentrations. These findings demonstrate a direct sensitive approach to determine interactions between proteins and particle/surface coatings important to diverse biotechnology applications.

Conformation-dominated surface antifouling and aqueous lubrication

Antifouling and aqueous lubrication are important properties for biomaterials, especially for those with implantation purposes. In order to better understand the polymer conformation dependence of the surface antifouling and lubrication properties, poly(ethylene glycol) (PEG) polymers with mono-functional and difunctional catechol anchors were designed and anchored on surface to adopt tail and loop conformations. Diblock and triblock copolymers with poly(dopamine methacrylamide) (PDMA) block as anchors and PEG block as the main body were synthesized and anchored on silicon surfaces by a "grafting to" strategy. The chemical composition, film thickness, and surface roughness of both coatings were controlled to be similar to give a direct comparison of looped brushes and tailed analogues. Then, the antifouling and surface friction behaviors were detected to verify the topological conformation effect of PEG polymer brushes. Results showed that PEG triblock copolymer modified surface exhibited an obviously better antifouling property and a lower friction coefficient of ∼0.011 than that of PEG diblock copolymer modified surface. Additionally, calculation and simulation results demonstrated that triblock copolymer had higher adsorption energy and anchored on surface with looped conformation. It is indicated that the strongly anchored PEG loops are effective for excellent antifouling and lubricating properties due to its strong hydration and steric hindrance. The conformation-dominated enhanced antifouling and reduced interfacial friction is an effective method for the development of excellent antifouling surfaces.

ROS‐Sensitive Degradable PEG–PCL–PEG Micellar Thermogel

A reactive oxygen species (ROS)-sensitive degradable polymer would be a promising material in designing a disease-responsive system or accelerating degradation of polymers with slow hydrolysis kinetics. Here, a thermogelling poly(ethylene glycol)-polycaprolactone-poly(ethylene glycol) (PEG-PCL-PEG or EG12 -CL20 -EG12 ) triblock copolymer with an oxalate group at the middle of the polymer is reported. The polymers form micelles with an average size of 100 nm in water. Thermogelation is observed in a concentration range of 8.0-37.0 wt%. In particular, the aqueous PEG-PCL-PEG triblock copolymer solutions are in a gel state at 37 °C in a concentration range of 25.0-37.0 wt%, whereas the aqueous PEG-PCL diblock copolymer solutions are in a sol state in the same concentration range at 37 °C. Thus, the gel depot could dissolve out once degradation of the triblock copolymers occurs at the oxalate group as confirmed by the in vitro experiment. In vivo gel formation is confirmed by injecting an aqueous PEG-PCL-PEG solution (36.0 wt%) into the subcutaneous layer of rats. The gel completely disappears in 21 d. A model polypeptide drug (cyclosporine A) is released over 21 d from the in situ formed gel. The micelle-based thermogel of PEG-PCL-PEG with ROS-triggering degradability is a promising injectable material for biomedical applications.

Verteporfin-Loaded Poly(ethylene glycol)-Poly(beta-amino ester)-Poly(ethylene glycol) Triblock Micelles for Cancer Therapy.

Amphiphilic polymers can be used to form micelles to deliver water-insoluble drugs. A biodegradable poly(ethylene glycol) (PEG)-poly(beta-amino ester) (PBAE)-PEG triblock copolymer was developed that is useful for drug delivery. It was shown to successfully encapsulate and pH-dependently release a water-insoluble, small molecule anticancer drug, verteporfin. PEG-PBAE-PEG micelle morphology was also controlled through variations to the hydrophobicity of the central PBAE block of the copolymer in order to evade macrophage uptake. Spherical micelles were 50 nm in diameter, while filamentous micelles were 31 nm in width with an average aspect ratio of 20. When delivered to RAW 264.7 mouse macrophages, filamentous micelles exhibited a 89% drop in cellular uptake percentage and a 5.6-fold drop in normalized geometric mean cellular uptake compared to spherical micelles. This demonstrates the potential of high-aspect-ratio, anisotropically shaped PEG-PBAE-PEG micelles to evade macrophage-mediated clearance. Both spherical and filamentous micelles also showed therapeutic efficacy in human triple-negative breast cancer and small cell lung cancer cells without requiring photodynamic therapy to achieve an anticancer effect. Both spherical and filamentous micelles were more effective in killing lung cancer cells than breast cancer cells at equivalent verteporfin concentrations, while spherical micelles were shown to be more effective than filamentous micelles against both cancer cells. Spherical and filamentous micelles at 5 and 10 μM respective verteporfin concentration resulted in 100% cell killing of lung cancer cells, but both micelles required a higher verteporfin concentration of 20 μM to kill breast cancer cells at the levels of 80% and 50% respectively. This work demonstrates the potential of PEG-PBAE-PEG as a biodegradable, anisotropic drug delivery system as well as the in vitro use of verteporfin-loaded micelles for cancer therapy.

Facile preparation of pH-responsive polyurethane nanocarrier for oral delivery

This study reports a novel one pot synthesis of pH-responsive nanocarrier for oral delivery of hydrophobic drug under gastrointestinal tract. Triblock copolymer MPEG-HTPB-MPEG was synthesized coupling of MPEG and HTPB using hexamethylene diisocyanate(HDI) and pH-responsive carboxylic acid group was attached to polybuthadiene backbone by thiol-ene click reaction in a facile and convenient procedure. The MPEG-HTPB (g-COOH)-MPEG block copolymers were self-organized into micelle assemblies in the water. The size and shape of the micelle assemblies were confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The nanocarriers have high drug loading ability for poorly water-soluble drug. The pH-responsive profile was demonstrated by pH-dependent swelling and in vitro drug release. <10.0% IBU was released under artificial gastric fluid after 2h, whereas an immediate release was observed under artificial intestinal fluid. The XTT assay indicated that the micelle obtained from PEG-HTPB (g-COOH)-PEG triblock copolymer are safe in a wide range of concentrations. The results show that pH-responsive PEG-HTPB (g-COOH)-PEG triblock copolymers are promising nanocarriers for the oral administration of hydrophobic drugs.

2-Mercaptopyridine as a new leveler for bottom-up filling of micro-vias in copper electroplating

In order to achieve a perfect bottom-up electroplated Cu filling with a minimal surface thickness, 2-mercaptopyridine (2-MP) was investigated as a new leveler for replacing Janus Green B (JGB) for bottom-up copper filling. Electrochemical impedence results indicate that 2-MP has a stronger suppression for Cu deposition than JGB. With the addition of 2-MP, the filling capability of the electroplating solution is improved significantly with the Cu thickness on surface decreasing from ∼16μm to ∼10μm. The interaction mechanisms of 2-MP, bis(3-sulfopropyl) disulfide (SPS), Cl− and tri-block copolymer of PEG and PPG with ethylene oxide terminal blocks (EPE) in the plating solution are studied by galvanostatic measurements (GMs). The acceleration effect of SPS and the inhibition effect of 2-MP on copper deposition occur in the presence of EPE, and the convection-dependent adsorption (CDA) behavior of additives usually occurs with the injection of four additives at optional concentrations. Further, it was found that when 1.0ppm 2-MP, 1.0ppm SPS and 200ppm EPE were injected into the basic electrolyte, the potential difference (Δh) value of the electrolyte became positive, and the bottom-up electroplated copper filling was obtained in the electrolyte in absence of Cl−. The interaction mechanisms of three additives for bottom-up filling have been investigated by GMs.

Structural insights into the effect of cholinium-based ionic liquids on the critical micellization temperature of aqueous triblock copolymers

Symmetrical poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEG-PPG-PEG) triblock copolymer with 82.5% PEG as the hydrophilic end blocks, and PPG as the hydrophobic middle block, was chosen to study the effect of ionic liquids (ILs) on the critical micellization temperature (CMT) of block copolymers in aqueous solution. In the present work, cholinium-based ILs were chosen to explore the effect of the anions on the copolymer CMT using fluorescence spectroscopy, dynamic light scattering (DLS), viscosity (η), FT-IR spectroscopy, nuclear magnetic resonance (NMR), and direct visualization of the various self-assembled nanostructures by scanning electron microscopy (SEM). The result suggests that ILs have the ability to decrease the CMT of the aqueous copolymer solution which is dependent on the nature of the anions of the ILs. The present study reveals that the hydrophobic part PPG of the copolymer has more influence on this behavior than the PEG hydrophilic part.

Metal-free oxygen reduction electrodes based on thin PEDOT films with high electrocatalytic activity

Oxygen reduction reaction (ORR) electrodes play an important role in the development of new battery and fuel cell technologies. However most of the presented electrode materials cannot provide the efficiency required for these applications, and/or they are based on economically unfavourable noble metals. In this article, multi-layer electrodes of high conductivity PEDOT prepared by vacuum vapour phase polymerization in the presence of a PEG–PPG–PEG triblock copolymer are used to fabricate a metal-free oxygen reduction electrode. After optimizing the main production parameters, measuring ORR performance of the metal-free PEDOT based electrodes confirms that they have the ability to deliver a stable electrocatalytic activity. A chemical treatment is also used for further enhancing the electrocatalytic activity of these electrodes. Depending on pH, the electrocatalytic activity of these treated electrodes reaches a higher or the same level as platinum based electrodes.

Reduction-degradable PEG-b–PAA-b–PEG triblock copolymer micelles incorporated with MTX for cancer chemotherapy

Reduction-breakable core–shell type polymeric micelles from reduction-degradable amphiphilic polyethylene glycol-b–polyamide amine-b–polyethylene glycol triblock copolymers (PEG-b–PAA-b–PEG) were prepared as new drug carriers of methotrexate (MTX) for cancer chemotherapy. The PEG-b–PAA-b–PEG copolymers were synthesized in a simple one-step process under mild condition through Michael addition. Spherical micelles with diameters ranging from 65 to 123nm were successfully fabricated from the copolymers. These micelles could effectively encapsulate the anti-cancer drug MTX in the core with drug loading content around 13%. The incorporation of MTX resulted in a little size increase but did not influence the morphology of micelles. The drug was hardly released from the micelles in normal condition without DDT as the reductant, but fast released up to 100% within 24h when the structure of micelle core was broken in the presence of DTT, thus provided a potential tool for tumor targeting delivery of MTX using the higher concentration of reductant in tumor tissues. The proliferation inhibition experiments demonstrate that MTX-encapsulated micelles show significant cytotoxicity to KB, HepG2 and 4T1 tumor cells, especiallythe 4T1 cells.

Synthesis, Characterization, and Evaluation of Pluronic-Based β-Cyclodextrin Polyrotaxanes for Mobilization of Accumulated Cholesterol from Niemann-Pick Type C Fibroblasts

Several lines of evidence suggest that β-cyclodextrin (β-CD) derivatives initiate the efflux of accumulated, unesterified cholesterol from the late endosomal/lysosomal compartment in Niemann Pick C (NPC) disease models. Unfortunately, repeated injections or continuous infusions of current β-CD therapies are required to sustain suppression of symptoms and prolong life. In an effort to make CD treatment a more viable option by boosting efficacy and improving pharmacokinetics, a library of Pluronic surfactant-based β-CD polyrotaxanes has been developed using biocompatible poly(ethylene glycol) (PEG)-polypropylene glycol (PPG)-PEG triblock copolymers. These compounds carry multiple copies of β-CD as shown by (1)H NMR, 2D nuclear Overhouser effect spectroscopy, gel permeation chromatography/multiangle light scattering, analytical ultracentrifugation analysis, matrix assisted laser desorption/ionization mass spectrometry, and diffusion-ordered spectroscopy. Analyses of free β-cyclodextrin contamination in the compounds were made by reverse phase high pressure liquid chromatography and hydrophilic interaction liquid chromatography. Dethreading kinetics were studied by reverse phase high pressure liquid chromatography, UV/vis, and (1)H NMR analysis. Filipin staining studies using npc2(-/-) fibroblasts show significant reversal of cholesterol accumulation after treatment with polyrotaxane compounds. The rate and efficacy of reversal is similar to that achieved by equivalent amounts of monomeric β-CD alone.

Modeling and self-assembly behavior of PEG–PLA–PEG triblock copolymers in aqueous solution

A series of poly(ethylene glycol)-polylactide-poly(ethylene glycol) (PEG-PLA-PEG) triblock copolymers with symmetric or asymmetric chain structures were synthesized by combination of ring-opening polymerization and copper-catalyzed click chemistry. The resulting copolymers were used to prepare self-assembled aggregates by dialysis. Various architectures such as nanotubes, polymersomes and spherical micelles were observed from transmission electron microscopy (TEM), cryo-TEM and atomic force microscopy (AFM) measurements. The formation of diverse aggregates is explained by modeling from the angle of both geometry and thermodynamics. From the angle of geometry, a "blob" model based on the Daoud-Cotton model for star polymers is proposed to describe the aggregate structures and structural changes with copolymer composition and molar mass. In fact, the copolymer chains extend in aqueous medium to form single layer polymersomes to minimize the system's free energy if one of the two PEG blocks is short enough. The curvature of polymersomes is dependent on the chain structure of copolymers, especially on the length of PLA blocks. A constant branch number of aggregates (f) is thus required to preserve the morphology of polymersomes. Meanwhile, the aggregation number (N(agg)) determined from the thermodynamics of self-assembly is roughly proportional to the total length of polymer chains. Comparing f to N(agg), the aggregates take the form of polymersomes if N(agg) ≈ f, and change to nanotubes if N(agg) > f to conform to the limits from both curvature and aggregation number. The length of nanotubes is mainly determined by the difference between N(agg) and f. However, the hollow structure becomes unstable when both PEG segments are too long, and the aggregates eventually collapse to yield spherical micelles. Therefore, this work gives new insights into the self-assembly behavior of PEG-PLA-PEG triblock copolymers in aqueous solution which present great interest for biomedical and pharmaceutical applications.

Dose-dependent sustained local release of dexamethasone from biodegradable thermosensitive hydrogel of PEG–PLGA–PEG triblock copolymers in the possible prevention of TMJ re-ankylosis (Arakeri’s TMJ release technique)

Temporomandibular joint (TMJ) ankylosis is a devastating anatomico-pathological condition which severely affects the quality of human health. Over the last 70years various treatments have been described to treat this distressing condition. But no single method has uniformly produced successful results. Although various surgical techniques have been improved periodically, the treatment results remain inefficient due to its recurrence as TMJ re-adhesion. Since recurrence remains as a problem in many cases, the TMJ ankylosis presents a major therapeutic challenge in head and neck surgery. The re-ankylosis is a unique phenomenon that so far has defied a full and logical explanation, based upon biological and mechanical factors that are linked together in a coherent fashion. Many factors have been implicated in the development of re-adhesion following TMJ surgery. But still the mechanism by which the TMJ re-adhesion develops is unclear. Hence, TMJ ankylosis demands an alternative effective treatment modality to prevent its recurrence as re-ankylosis. This paper postulates some critical biological factors responsible for re-ankylosis based on which a novel treatment modality is also proposed.

Plasticization of polylactide with block copolymers of ethylene glycol and propylene glycol

AbstractIn this study, plasticization of polylactide (PLA) with PEG–PPG–PEG triblock copolymers was examined. Two different copolymers were utilized, with molecular weight of 1100 and 1900 g mol−1, and with PEG contents of 10 and 50 wt %, respectively. A PPG plasticizer with molecular weight of 1000 g mol−1, close to that of PPG block in the copolymers, was also used for comparison. Melt blends containing 10 and 15 wt % of the plasticizers were prepared. Thermal properties, mechanical properties, and structure of quenched and annealed films of the blends were studied. The crystallization driven phase separation occurred in all the annealed blends but led to different structures depending on the plasticizer used. Distinct inclusions of the plasticizer were visible under the scanning electron microscope only in PLA with PPG but not in the blends of PLA with the copolymers. The drawability of the plasticized systems was improved when compared with neat PLA. In the quenched and annealed blends, elongations at break at the level of 5 and 0.7, respectively, were reached. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Preparation and in vitro evaluation of doxorubicin-loaded Fe3O4 magnetic nanoparticles modified with biocompatible copolymers

BackgroundSuperparamagnetic iron oxide nanoparticles are attractive materials that have been widely used in medicine for drug delivery, diagnostic imaging, and therapeutic applications. In our study, superparamagnetic iron oxide nanoparticles and the anticancer drug, doxorubicin hydrochloride, were encapsulated into poly (D, L-lactic-co-glycolic acid) poly (ethylene glycol) (PLGA-PEG) nanoparticles for local treatment. The magnetic properties conferred by superparamagnetic iron oxide nanoparticles could help to maintain the nanoparticles in the joint with an external magnet.MethodsA series of PLGA:PEG triblock copolymers were synthesized by ring-opening polymerization of D, L-lactide and glycolide with different molecular weights of polyethylene glycol (PEG2000, PEG3000, and PEG4000) as an initiator. The bulk properties of these copolymers were characterized using 1H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy, and differential scanning calorimetry. In addition, the resulting particles were characterized by x-ray powder diffraction, scanning electron microscopy, and vibrating sample magnetometry.ResultsThe doxorubicin encapsulation amount was reduced for PLGA:PEG2000 and PLGA:PEG3000 triblock copolymers, but increased to a great extent for PLGA:PEG4000 triblock copolymer. This is due to the increased water uptake capacity of the blended triblock copolymer, which encapsulated more doxorubicin molecules into a swollen copolymer matrix. The drug encapsulation efficiency achieved for Fe3O4 magnetic nanoparticles modified with PLGA:PEG2000, PLGA:PEG3000, and PLGA:PEG4000 copolymers was 69.5%, 73%, and 78%, respectively, and the release kinetics were controlled. The in vitro cytotoxicity test showed that the Fe3O4-PLGA:PEG4000 magnetic nanoparticles had no cytotoxicity and were biocompatible.ConclusionThere is potential for use of these nanoparticles for biomedical application. Future work includes in vivo investigation of the targeting capability and effectiveness of these nanoparticles in the treatment of lung cancer.

Controlled thermal gelation of poly(ε-caprolactone)/poly(ethylene glycol) block copolymers by modifying cyclic ether pendant groups on poly(ε-caprolactone)

The control of the thermal gelation behavior of amphiphilic copolymers based on PEGylated hydrophobic polymers is important for applications in drug administration and controlled release. This paper studied a new method to control the thermal gelation behavior of the amphiphilic copolymers by structure modification of hydrophobic segments. A kind of triblock copolymer of PEG and modified poly(e-caprolactone) (PCL) with cyclic ether pendant groups, i.e. poly(e-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone)-poly(ethylene glycol)-poly(e-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) triblock copolymers (PECT) were synthesized through the ring-opening copolymerization of e-caprolactone and 1,4,8-trioxa[4.6]spiro-9-undecanone (TOSUO) in the presence of poly(ethylene glycol). The structure and thermal gelation behavior of PECT were characterized by 1H NMR, FT-IR, GPC, XRD, DSC and DLS, etc. The study results indicated that the introduction of cyclic ether pendant groups on the PCL backbone not only reduced the crystallinity of PCL but also increased the hydrophilicity of the hydrophobic phase, which provides perfect dispersity of PECT in water and allows a more excellently controlled thermal gelation behavior than the PCL-PEG-PCL block copolymer. PECT powder can directly disperse in water to form a stable nanoparticle aqueous dispersion even with a high content of hydrophobic block (the weight ratio of PCL to PEG is nearly 3). Further, the PECT nanoparticle aqueous dispersion at higher concentration performed sol–gel–sol transition behavior with the temperature increasing from ambient or lower temperature, and the transition temperature and gelation behavior could be adjusted by the content of the cyclic ether pendant groups on the PCL segments. Significantly, avoiding the pre-quenching treatment that is needed for PCL-PEG-PCL gelation, the PECT nanoparticle aqueous dispersions, which are injectable fluids at ambient temperature and form a gel at 37 °C quickly, provide an injectable in situ gel system for clinical applications with the advantages of convenient dosage, administration, storage, and prescription. Therefore, the PECT thermal hydrogel system is expected to have potential applications in drug delivery and tissue engineering.

Biophysical Effects of a Novel Biodegradable Copolymer on the Repair of Damaged Neural Membranes

The pathophysiology of Spinal cord injury (SCI) is involved primary mechanical injury followed by secondary delayed injury. Neural membrane is the most susceptible part of the cell and most of the time mechanical injury results in axolemma disruption and failure to function as an electrical and ionic barrier. This leads to blockage of nerve impulse conduction, deregulation of ionic gradients; free radical associated lipid peroxidation of membrane and increased influx of calcium ions that activates calpain and caspase-dependent cell death cascades. Thus immediate membrane repair can prevent various destructive processes, restoring of the physicochemical balance of the cytoplasm and ultimate functional recovery in neurons. Several degradable polymers and surfactants including PEG, Poloxamer 188, and poloxamine 1107 have shown to be effective in sealing and halting progressive permeabilization. Here, we applied ultrasound wave as mechanical insult to make transient breaches in membrane to simulate membrane damage in SCI and used a novel triblock copolymer of PEG-(fumaric-sebacic acids)-PEG to seal membrane breaches. Cell survival and membrane integrity were checked by MTT assay and Trypan blue exclusion test respectively. The results showed that this copolymer can be a promising candidate for membrane sealing. Now we are assessing the effects of this polymer on in vivo spinal cord evoked potential (SCEP).

Novel pH-sensitive polyacetal-based block copolymers for controlled drug delivery

The principal aim of this study was to synthesize and characterize pH-sensitive biodegradable triblock copolymers containing a hydrophobic polyacetal segment for controlled drug delivery. Poly(ethylene glycol)–poly(ethyl glyoxylate)–poly(ethylene glycol) (PEG–PEtG–PEG) triblock copolymers with PEG molecular weights 500 (PEtG–PEG 500) and 750 (PEtG–PEG 750) were synthesized by PEtG end-capping with methoxy PEG via a carbamate linkage. Synthesized amphiphilic PEG–PEtG–PEG was characterized by 1H NMR spectroscopy. Molecular weights of PEtG–PEG 500 and PEtG–PEG 750 were determined to be 2823 and 3387, respectively, by gel permeation chromatography. The polymers with a biodegradable polyacetal block underwent pH-dependent degradation via an acid-catalyzed hydrolysis. Paclitaxel (PTX)-loaded polymeric micelles were prepared by a dialysis method and the amount of PTX incorporated into the polymeric micelle formulations was 45,000 times greater than the water solubility of PTX at room temperature. The polymeric micelles prepared from the amphiphilic PEG–PEtG–PEG triblock copolymers have released the loaded PTX in a pH-dependent manner. The novel PEtG-based amphiphilic block copolymers can find applications for targeted and controlled drug delivery to the acidic environments found in tumors and intracellular compartments.

Synthesis and characterization of PEG–PCL–PEG triblock copolymers as carriers of doxorubicin for the treatment of breast cancer

AbstractTriblock copolymers of monomethoxy poly(ethylene glycol) (mPEG) and ε‐caprolactone (CL) were prepared with varying lengths of poly(ε‐caprolactone) (PCL) compositions and a fixed length of mPEG segment. The molecular characteristics of triblock copolymers were characterized by 1H NMR, gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FT‐IR), X‐ray diffraction (XRD), and differential scanning calorimetry (DSC). These amphiphilic linear copolymers based on PCL hydrophobic chain and hydrophilic mPEG ending, which can self‐assemble into nanoscopic micelles with their hydrophobic cores, encapsulated doxorubicin (DOX) in an aqueous solution. The particle size of prepared micelles was around 40–92 nm. The DOX loading content and DOX loading efficiency were from 3.7–7.4% to 26–49%, respectively. DOX‐released profile was pH‐dependent and faster at pH 5.4 than pH 7.4. Additionally, the cytotoxicity of DOX‐loaded micelles was found to be similar with free DOX in drug‐resistant cells (MCF‐7/adr). The great amounts of DOX and fast uptake accumulated into the MCF‐7/adr cells from DOX‐loaded micelles suggest a potential application in cancer chemotherapy. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

Biodegradable Thermogelling Poly[(R)-3-hydroxybutyrate]-Based Block Copolymers: Micellization, Gelation, and Cytotoxicity and Cell Culture Studies

A series of biodegradable multiblock poly(ester urethane)s having poly[(R)-3-hydroxybutyrate] (PHB), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) segments was prepared. The critical micellization concentration (CMCs) of these water-soluble poly(ester urethane)s were determined at different temperatures in order to calculate the thermodynamic parameters for the process of micelle formation. The process for micelle formation was found to be entropy-driven. The thermogelling behavior of the aqueous polymer solution was studied by (1)H and (13)C NMR spectroscopy at different temperatures. We obtained valuable molecular level information regarding the state of the copolymer in solution based on the variation of the peak widths. Cytotoxicity studies performed on the extracts of the copolymer gel indicate good cell compatibility. Cells attach on the surface of the gel much better than on the commercially available PEG-PPG-PEG triblock copolymer. These studies indicate a potential for the copolymer gel to be used for tissue engineering applications.

Preparation of intermediary layer crosslinked micelles from a photocrosslinkable amphiphilic ABC triblock copolymer

To prepare intermediary layer crosslinked micelles, a photocrosslinkable amphiphilic ABC triblock copolymer, poly(ethylene glycol)- b-poly(2-cinnamoyloxyethyl methacrylate)- b-poly(methyl methacrylate) (PEG–PCEMA–PMMA), was synthesized and its micellar characteristics were investigated. The triblock copolymer of PEG- b-poly(2-hydroxyethyl methacrylate)- b-PMMA (PEG–PHEMA–PMMA) ( M n = 9800 g/mol, M w/ M n = 1.33) was first polymerized by activators generated by electron transfer (AGET) atom transfer radical polymerization (ATRP) using a PEG macroinitiator in a mixed solvent of anisole/2-isopropanol (3/1 v/v). The middle block of the copolymer was then functionalized with cinnamoyl chloride. The degrees of polymerization of the PEG, PHEMA, and PMMA blocks were 113, 18 and 21, respectively. The critical micelle concentration (CMC) of the PEG–PCEMA–PMMA was 0.011 mg/mL. The PEG–PCEMA–PMMA micelles were spherically shaped with an average diameter of 43 nm. The intermediary layer of the PEG–PCEMA–PMMA micelles was crosslinked by UV irradiation. Not all of the cinnamate groups underwent photocrosslinking probably due to a lack of other cinnamate groups in their immediate vicinity. However, the degree of photocrosslinking of the intermediary layer of the PEG–PCEMA–PMMA micelles was sufficient to give excellent colloidal stability, even in different external environments.