PEG Molecular Weight Research Articles

Tumor Microenvironment Stimuli-Responsive Polymeric Prodrug Micelles for Improved Cancer Therapy.

The discovery of nano drug delivery system has rendered a great hope for improving cancer therapy. However, there are some inevitable obstacles that constrain its development, such as the physical and biological barriers, the toxicity of carrier materials and the physiological toxicity of drugs. Here, we report a polymeric prodrug micelle (PPM) with pH/redox dual-sensitivity, which was prepared using methoxy poly (ethylene glycol) (mPEG) with favorable biosafety to improve cancer therapy. The tumor microenvironment stimuli-responsive PPMs were prepared and characterized in vitro and in vivo. Our data displayed that the PPMs with excellent biocompatibility exhibited the stimuli-responsive drug release behavior under the microenvironment of cancer cells, superior cellular internalization and lower cytotoxicity. A new method to control drug release behavior was proposed by comparing the release behavior of PPMs formed by PEG of different molecular weight. Furthermore, the fabricated PPMs exhibited the "oral-like" blood concentration curve, improved biodistribution, reduced tissue toxicity and excellent antitumor efficiency in vivo. Consistently, these results indicated that PPMs improved chemotherapeutic efficiency and reduced side effects of the model drug doxorubicin (DOX). The prepared pH/redox dual-sensitive PPM enhanced the chemotherapy effect on the tumor site while reducing the physiological toxicity of DOX. Graphical Abstract.

Synthesis of PEG-grafted boron doped Si nanocrystals.

Silicon nanocrystals are intriguing materials for biomedical imaging applications because of their unique optical properties and biological compatibility. We report a new surface functionalization route to synthesize biological buffer soluble and colloidally stable silicon nanocrystals, which is enabled by surface boron doping. Harnessing the distinctive Lewis acidic boron surface sites, postsynthetic modifications of plasma synthesized boron doped nanocrystals were carried out with polyethylene glycol (PEG-OH) ligands in dimethyl sulfoxide under photochemical conditions. The influence of PEG concentration, PEG molecular weight, and boron doping percentage on the nanocrystal solubility in a biological buffer has been investigated. The boron doping facilitates the surface functionalization via two probable pathways, by providing excellent initial dispersiblity in polar solvents and providing available acidic boron surface sites for bonding. These boron doped silicon nanocrystals have nearly identical absorption features as intrinsic silicon nanocrystals, indicating that they are promising candidates for biological imaging applications.

Density, Viscosity, Refractive Index and Excess Properties of Binary and Ternary Solutions of Poly (Ethylene Glycol), Sulfate Salts and Water at 298.15 K

The refractive index (n_D ), viscosity(η) and density (ρ) values of the poly (ethylene glycol) (PEG) 300,400 and 600 + water , zinc sulfate, magnesium sulfate and aluminum sulfate + water binary and their ternary solutions have been measured at 298.15 K and atmospheric pressure. In this work, the effect of concentration (0.05-0.3 %w/w), PEG molecular weight and type of cation on the n_D,η and ρ of the mention binary and ternary mixtures have been explored. Furthermore, the experimental measurements were applied to compute the refractive index deviation (Δn_D), viscosity deviation (Δƞ), the apparent specific volume (V_φ), excess molar volume (V^E) and excess Gibbs energy of activation for viscous flow〖ΔG〗^(≠E)) for the analysis of the behavior of the solutions. Δn_D and V^E were fitted to the Cibulka and a third-order Redlich–Kister polynomial models to estimate the interaction parameters. The intermolecular interactions between the mixing components were demonstrated by the obtained data from the calculated functions.

Influence of surfactants and surfactant-coated IONs on the rate of alkaline hydrolysis of procaine in the presence of PEG

The influence of surfactant coated iron oxide nanocomposites (Surf-IONs) and surfactants on the rate of alkaline hydrolysis of procaine hydrochloride (2-diethylaminoethyl-4-aminobenzoic acid) in the presence of poly(ethylene glycol) (PEG) have been investigated under the varying reaction conditions. The nanoparticles were synthesised using the co-precipitation method and were characterised using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Vibrating sample magnetometer (VSM) and Thermogravimetric analysis (TGA). The concentration of NaOH was taken in overabundance over [procaine] for maintaining the reactions under pseudo-first-order conditions. The kinetic effect of poly(ethylene glycol); PEG of molecular weights 1500, 4000, 6000, and 8000 with the cetyltrimethylammonium bromide; CTABr and sodium dodecyl sulphate; SDS (either free or coated on iron oxide nanoparticles) were studied. A fall in the values of the rate constant on increasing the [surfactant] or [Surf-IONs] at fixed [PEG] was observed. The kψ-[PEG-surfactant] profile was treated using the pseudophase model, and pseudophase ion exchange model and the kinetic parameters were determined. The binding constant of procaine with PEG-surfactant aggregates was found to be lower than the respective micelles in the absence of PEG. The increase in the molecular weights of PEG decreased the values of binding constants and equilibrium constants.

Amphiphilic PLGA‐PEG‐PLGA triblock copolymer nanogels varying in gelation temperature and modulus for the extended and controlled release of hyaluronic acid

ABSTRACTDifferent compositional parameters of poly(D,L‐lactic‐co‐glycolic acid)‐b‐poly(ethylene glycol) triblock copolymers (PLGA‐PEG) were varied to analyze their effect on gel formation and mechanical properties. Parameters such as hydrophilic/hydrophobic ratio (PLGA/PEG ratio), lactic acid/glycolic acid ratio (LA/GA ratio), PEG molecular weight (PEG Mw), polymer solution concentration, copolymer molecular weight (Mw), and polydispersity index (PDI) were studied in this work. For copolymers with PEG Mw of 1500 Da, gelation temperature (34–37 °C) was affected by D,L‐LA/GA ratio and Mw; while modulus was affected by LA/GA ratio, Mw, and Mn. Based on the parametric study, an injectable, thermoresponsive hyaluronic acid (HA) delivery platform was designed for ocular applications. PLGA‐PEG copolymers with D,L‐LA/GA ratio of 15/1, PLGA/PEG ratio of 2/1, PEG Mw of 1500 Da, and Mw of about 6 KDa gelled at 35 °C, were optically transparent, had a modulus less than 350 Pa and were used for HA release studies. This work also demonstrates, for the first time, an extended and controlled release of HA, beyond 2 weeks, from injectable hydrogels modified with a noncovalent interacting agent, poly(L‐lysine). Smaller PLL chains slowed down the HA release kinetics, while larger PLL chains produced a release profile similar to the nonmodified hydrogels. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48678.

Optimization, stabilization, and characterization of amphotericin B loaded nanostructured lipid carriers for ocular drug delivery.

The current study sought to formulate, optimize, and stabilize amphotericin B (AmB) loaded PEGylated nanostructured lipid carriers (NLC) and to study its ocular biodistribution following topical instillation. AmB loaded PEGylated NLC (AmB-PEG-NLC) were fabricated by hot-melt emulsification followed by high-pressure homogenization (HPH) technique. 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] (mPEG-2K-DSPE) was used for surface PEGylation. mPEG-DSPE with different PEG molecular weight, 1 K, 2 K, 5 K, 10 K, and 20 K, were screened for formulation stability. Furthermore, the AmB loaded PEGylated (2K) NLC (AmB-PEG2K-NLC) was optimized using Box-Behnken design with respect to the amount of AmB, castor oil, mPEG-2K-DSPE, and number of high-pressure homogenization cycles as the factors; particle size, zeta potential, PDI, entrapment efficiency, and loading efficiency as responses. Stability of the optimized AmB-PEG2K-NLC was assessed over 4 weeks, at 4 °C as well as 25 °C and effect of autoclaving was also evaluated. AmB-PEG2K-NLC were tested for their in vitro antifungal activity against Candida albicans (ATCC 90028), AmB resistant Candida albicans (ATCC 200955) and Aspergillus fumigatus (ATCC 204305). Cytotoxicity of AmB-PEG2K-NLC was studied in human retinal pigmented epithelium cells. In vivo ocular biodistribution of AmB was evaluated in rabbits, following topical application of PEGylated NLCs or marketed AmB preparations. PEGylation with mPEG-2K-DSPE prevented leaching of AmB and increased the drug load significantly. The optimized formulation was prepared with a particle size of 218 ± 5 nm; 0.3 ± 0.02 PDI, 4.6 ± 0.1% w/w drug loading, and 92.7 ± 2.5% w/w entrapment efficiency. The optimized colloidal dispersions were stable for over a month, at both 4 °C and 25 °C. AmB-PEG2K-NLCs showed significantly (p < 0.05) better antifungal activity in both wild-type and AmB resistant Candida strains and, was comparable to, or better than, commercially available parenteral AmB formulations like Fungizone™ and AmBisome®. AmB-PEG2K-NLC did not show any toxicity up to a highest concentration of 1% (v/v) (percent formulation in medium). Following topical instillation, AmB was detected in all the ocular tissues tested and statistically significant (p > 0.05) difference was not observed between the formulations tested. An optimized autoclavable and effective AmB-PEG2K-NLC ophthalmic formulation with at least one-month stability, in the reconstituted state, has been developed.

Spontaneous growth of gold nanoclusters to form gold nanoparticles in the presence of high molecular weight poly(ethylene glycol)

Simple and convenient preparation of metal nanoparticles has been a challenging issue to overcome in nano-technologies. To address this, spontaneous growth of gold nanoclusters to form gold nanoparticles in the presence of high molecular weight poly(ethylene glycol) (PEG) was studied under ambient conditions. Gold nanoclusters with a particle size of ∼2 nm spontaneously grew to form larger gold nanoparticles with a plasmonic absorption band at 520 nm only when in the presence of structurally organized PEG with a molecular weight of at least 2 × 106 g/mol, producing a pinkish colored solution. UV–vis absorption spectra indicate the existence of two steps responsible for gold nanocluster growth to form gold nanoparticles. The first step involves an increase in the absorbance of the spectral band at 520 nm during the first 10 min due to aggregation of gold nanoclusters. The second step is the broadening of this band at the same wavelength as a result of fusion followed by growth of the gold nanoclusters. Redox potentials and transmission electron microscopy (TEM) images reveal that structurally organized high molecular weight PEG induces aggregation of the gold nanoclusters and their subsequent growth to form larger nanoparticles, which exhibit plate-like triangular structures with sharp edges. Our study unveils the role that PEG plays in the growth process from gold nanoclusters to gold nanoparticles.

Mono-PEGylates of exenatide in branched and dimeric structures can improve in vivo stability and hypoglycemic bioactivity

Exenatide, a synthetic version of exendin-4, is a glucagon-like peptide-1 receptor agonist (GLP-1RA) used for treating diabetes, but its relatively short half-life is a major disadvantage. In this study, we attempted residue-specific mono-PEGylation to the middle of the amino acid backbone to extend its in vivo half-life. Exenatide was point-mutated from Lys to Cys at the 12th residue to yield a variant (K12C), and PEG-maleimide of varying molecular weights (MW) (5, 10, 20, 40 kD) was site-specifically conjugated to yield a mono-PEGylate with branched T-shape molecular structure. In another approach, we conjugated a bis-maleimide PEG (10 kD) to the middle of two K12Cs to yield an H-shape homodimer PEGylate In vitro bioactivity assays indicated that: (1) PEGylates conjugated with higher MW PEG lead to stronger receptor binding, (2) the branched form was superior to the linear configuration in the binding, and (3) both T-shape and H-shape mono-PEGylates demonstrated better potency than the native exenatide, evidenced by lower EC50. Db/db mouse experiments to evaluate in vivo hypoglycemic activity indicated that: (1) all mono-PEGylates resulted in improved glucose tolerance compared to the native exenatide, (2) the homodimer PEGylate demonstrated much stronger hypoglycemic activity, especially during the initial period, and (3) the H-shape and T-shape mono-PEGylates (40 kD) maintained hypoglycemia for up to ca. 168 and 140 h, representing approximately 12- and 14-fold increase, respectively, compared with the native exenatide. Our findings suggest that the exenatide mono-PEGylates in unclassical molecular structures can improve in vivo pharmacokinetics properties.

Unusual effect of flow rate on retention in analytical supercritical fluid chromatography exemplified by polyethylene glycol separation

We report a case of a peculiar effect of flow rate on retention in a separation of polyethylene glycol oligomers via supercritical fluid chromatography. During method development, we tested flow rate gradients and notices that for some PEG oligomers retention times at flow rate gradient were lower than at constant flow with the largest flow rate value used in a gradient. For instance, at BEH stationary phase and CO2−MeOH gradient from 10 to 35% at 20 min a PEG oligomer having mass of 1225 Da has a retention time 14 min at 1 mL/min flow rate, 10.3 at 2 mL/min and 9.5 min at 1–2 mL/min flow rate gradient. The effect is not unified for all PEG oligomers, it occurs only starting from a particular PEG molecular weight which depends on the stationary phase type and/or mobile phase conditions. We believe that such an unusual flow rate effects can happen in SFC on various occasions, not exclusively for flow rate gradients, and thus should be taken into account during method development or method transfer.

Maleimide-functionalised PLGA-PEG nanoparticles as mucoadhesive carriers for intravesical drug delivery

Low permeability of the urinary bladder epithelium, poor retention of the chemotherapeutic agents due to dilution and periodic urine voiding as well as intermittent catheterisations are the major limitations of intravesical drug delivery used in the treatment of bladder cancer. In this work, maleimide-functionalised poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG-Mal) nanoparticles were developed. Their physicochemical characteristics, including morphology, architecture and molecular parameters have been investigated by means of dynamic light scattering, transmission electron microscopy and small-angle neutron scattering techniques. It was established that the size of nanoparticles was dependent on the solvent used in their preparation and molecular weight of PEG, for example, 105 ± 1 nm and 68 ± 1 nm particles were formed from PLGA20K-PEG5K in dimethyl sulfoxide and acetone, respectively. PLGA-PEG-Mal nanoparticles were explored as mucoadhesive formulations for drug delivery to the urinary bladder. The retention of fluorescein-loaded nanoparticles on freshly excised lamb bladder mucosa in vitro was evaluated and assessed using a flow-through fluorescence technique and Wash Out50 (WO50) quantitative method. PLGA-PEG-Mal nanoparticles (NPs) exhibited greater retention on urinary bladder mucosa (WO50 = 15 mL) compared to maleimide-free NPs (WO50 = 5 mL). The assessment of the biocompatibility of PEG-Mal using the slug mucosal irritation test revealed that these materials are non-irritant to mucosal surfaces.

PEGylated β-cyclodextrins: Click synthesis and in vitro biological insights

We present three easily rationalized star-shaped PEGylated β-cyclodextrin (βCD) derivatives synthesized via conjugation of different molecular weight PEG chains (5000, 2000, and 550 Da) to the βCD primary face by click chemistry (βCD-PEG5000, βCD-PEG2000, βCD-PEG550 respectively). βCDPEG systems are envisioned to further carry bioactive molecules, therefore, their interactions with biological interfaces must be determined at an early stage of development. Hence, the effect of βCDPEGs chain length on cell viability was investigated. To this aim, three models were selected: Vero cells for their fibroblast-like features; HeLa cells that are commonly used for preliminary viability screening; and human peripheral monocytes which are macrophage precursors. Of the three pegylated derivatives, βCD-PEG550 was the one that significantly affected HeLa cells and human monocytes viability. Despite the popularity of PEGylation approach, our results underscore the importance of careful and systematic PEGylated materials design for their future success in drug delivery systems.

Sustained Release of Vascular Endothelial Growth Factor from Poly(ε-caprolactone-PEG-ε-caprolactone)-b-Poly(l-lactide) Multiblock Copolymer Microspheres.

Vascular endothelial growth factor (VEGF) is the major regulating factor for the formation of new blood vessels, also known as angiogenesis. VEGF is often incorporated in synthetic scaffolds to promote vascularization and to enhance the survival of cells that have been seeded in these devices. Such applications require sustained local delivery of VEGF of around 4 weeks for stable blood vessel formation. Most delivery systems for VEGF only provide short-term release for a couple of days, followed by a release phase with very low VEGF release. We now have developed VEGF-loaded polymeric microspheres that provide sustained release of bioactive VEGF for 4 weeks. Blends of two swellable poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone)-b-poly(l-lactide) ([PCL–PEG–PCL]-b-[PLLA])-based multiblock copolymers with different PEG content and PEG molecular weight were used to prepare the microspheres. Loading of the microspheres was established by a solvent evaporation-based membrane emulsification method. The resulting VEGF-loaded microspheres had average sizes of 40–50 μm and a narrow size distribution. Optimized formulations of a 50:50 blend of the two multiblock copolymers had an average VEGF loading of 0.79 ± 0.09%, representing a high average VEGF loading efficiency of 78 ± 16%. These microspheres released VEGF continuously over 4 weeks in phosphate-buffered saline pH 7.4 at 37 °C. This release profile was preserved after repeated and long-term storage at −20 °C for up to 9 months, thereby demonstrating excellent storage stability. VEGF release was governed by diffusion through the water-filled polymer matrix, depending on PEG molecular weight and PEG content of the polymers. The bioactivity of the released VEGF was retained within the experimental error in the 4-week release window, as demonstrated using a human umbilical vein endothelial cells proliferation assay. Thus, the microspheres prepared in this study are suitable for embedment in polymeric scaffolds with the aim of promoting their functional vascularization.

Plasmin-Cleavable Nanoparticles for On-Demand Release of Morphogens in Vascularized Osteogenesis.

The objective of this work was to engineer self-assembled nanoparticles (NPs) for on-demand release of bone morphogenetic protein-2 (BMP2) and vascular endothelial growth factor (VEGF) in response to enzymes secreted by the migrating human mesenchymal stem cells (hMSCs) and human endothelial colony forming cells (ECFCs) to induce osteogenesis and vasculogenesis. Gene expression profiling experiments revealed that hMSCs and ECFCs, encapsulated in osteogenic/vasculogenic hydrogels, expressed considerable levels of plasminogen, urokinase plasminogen activator and its receptor uPAR, and tissue plasminogen activator. Therefore, the plasmin-cleavable lysine-phenylalanine-lysine-threonine (KFKT) was used to generate enzymatically cleavable NPs. The acetyl-terminated, self-assembling peptide glycine-(phenylalanine)3GFFF-ac and the plasmin-cleavable GGKFKTGG were reacted with the cysteine-terminated CGGK(Fmoc/MTT) peptide through the MTT and Fmoc termini, respectively. The difunctional peptide was conjugated to polyethylene glycol diacrylate (PEGDA) with molecular weights (MW) ranging from 0.5 to 7.5 kDa, and the chain ends of the PEG-peptide conjugate were terminated with succinimide groups. After self-assembly in aqueous solution, BMP2 was grafted to the self-assembled, plasmin-cleavable PEG-based (PxSPCP) NPs for on-demand release. The NPs' stability in aqueous solution and that of the grafted BMP2 were strongly dependent on PEG MW. P2SPCP NPs showed high particle size stability, BMP2 grafting efficiency, grafted protein stability, and high extent of osteogenic differentiation of hMSCs. The localized and on-demand release of BMP2 from PxSPCP NPs coencapsulated with hMSCs in the linear polyethylene glycol-co-lactide acrylate patterned hydrogel with microchannels encapsulating hMSCs + ECFCs and VEGF-conjugated nanogels resulted in the highest extent of osteogenic and vasculogenic differentiation of the encapsulated cells compared to directly added BMP2/VEGF. The on-demand release of BMP2 from PxSPCP NPs not only enhances osteogenesis and vasculogenesis but also potentially reduces many undesired side effects of BMP2 therapy in bone regeneration.

Electrokinetic assessment of RNase A species and innovative PEG-grafted agarose-based resins used in downstream processing of PEGylated proteins

Detailed study of the governing mechanisms of hydrophobic interaction chromatography in protein purification plays a key role in the design of separation systems. In our previous work, an innovative covalently bonded poly(ethylene glycol) (PEG) to Sepharose® 6B resin was developed. It could successfully separate PEGylated ribonuclease A (RNase A) species in a single chromatographic step (Hernández-Martínez and Aguilar, 2014), however, its electrokinetic profile has not been evaluated. The aim of this work was to study electrokinetics of RNase A species, unactivated, activated and activated-PEGylated Sepharose® 6B resins, and 5–40 kDa PEGylated resins. Electric potential, mobility and conductivity of resins was determined in presence of 0.025 M potassium phosphate buffer pH 7.0 supplemented with ammonium sulfate. Scanning electron microscopy and infrared spectroscopy techniques were used to characterize the resins. All protein and resins surfaces were negatively charged at pH 7.0 and ζ potential was dependent on electrolyte ion concentration. Variation in PEG molecular weight caused variation in ζ potential at low electrolyte concentrations. Morphology of resins did not change after resin PEGylation, however, size of particles ranged between 8–55 μm. These results contribute to electrokinetics understanding of RNase A and PEG-grafted resins, providing electric characterization of their surfaces, which is essential in the design, improvement and problem-solving in chromatographic methods for PEGylated species purification.

Structural and Physicochemical Properties and Biocompatibility of Linear and Looped Polymer-Capped Gold Nanoparticles.

Various polymer brushes with linear and looped conformations have gained considerable attention in the application of biomaterials and nanotechnology. In this work, the linear and looped polymer brush shells based on PEG-SH and SH-PEG-SH chains binding to gold nanoparticles (AuNPs) are synthesized. The structure and topology of the PEGylated AuNPs are systematically investigated. The basic physicochemical parameters of these PEGylated AuNPs such as hydrodynamic size, grafting density, hydrophilicity, colloidal stability, and biocompatibility are determined intensively. The looped polymer topology can remarkably alter physicochemical properties of polymer brushes compared with the linear counterparts. When the molecular weight of PEG is low (1 and 5 kDa), the looped polymer shells have smaller hydrodynamic size and lower grafting density than their linear analogues; when the molecular weight of PEG is high (10 kDa), the looped shells are much thicker and denser than the linear ones. Interestingly, the looped PEGs on AuNPs are more stable in a high-salt environment and have better hydrophilicity, which endow excellent biocompatibility, including protein resistance and cell viability. These results provide a simple approach to design polymer brushes with different topologies on AuNPs, improve the biocompatibility of hybrid AuNPs, and acquire the potential application in the biomedical field.

Dual Responsive Polymersomes for Gold Nanorod and Doxorubicin Encapsulation: Nanomaterials with Potential Use as Smart Drug Delivery Systems.

In the present study, poly(ethylene glycol)-b-poly(N,N-diethylaminoethyl methacrylate) (PEG-b-PDEAEM) amphiphilic block copolymers were synthetized by reversible addition-fragmentation chain transfer (RAFT) polymerization using two different macro chain transfer agents containing PEG of 2000 and 5000 g/mol and varying the length of the PDEAEM segment. From the obtained block copolymers, polymersome type nanometric aggregates were obtained by two different techniques. By direct dispersion, particle diameters around 200 nm were obtained, while by solvent exchange using THF and water, the obtained diameters were around 100 nm. These block copolymers were used to encapsulate gold nanorods and doxorubicin (DOX) with good efficiencies to obtain nanomaterials with potential use as dual stimuli-sensitive drug delivery systems for combined anticancer therapies. Drug delivery studies showed that the release rate of DOX was accelerated when the pH was lowered from 7.4 to 5.8 and also when the systems were irradiated with a NIR laser at pH 7.4. The combination of lower pH and near infrared (NIR) irradiation resulted in higher drug release only in the case of polymersomes with lower molecular weight PEG.

A nano-sized blending system comprising identical triblock copolymers with different hydrophobicity for fabrication of an anticancer drug nanovehicle with high stability and solubilizing capacity.

Background: A very common and simple method (known as the blending method) to formulate drug delivery systems with required properties is to physically mix amphiphilic block copolymers with different hydrophobicity. In addition to its simplicity, this blending strategy could help avoid the time and effort involved in the synthesis of block copolymers with the desired structure required for specific drug formulations.Purpose: We used the blending strategy to design a system that could overcome the problem of high hydrophobicity and be a good candidate for drug product development using PEG-PLA-PEG triblock copolymers.Methods: Two types of PEG-PLA-PEG triblock copolymers with similar (long) PLA molecular weights (MWs) and different PEG MWs were synthesized. The micellar formulations were prepared by blending the two block copolymers in various ratios. The size and stability of the blending systems were subsequently investigated to optimize the formulations for further studies. The loading properties of doxorubicin or paclitaxel into the optimized blending system were compared to that in mono systems (systems composed of only a single type of triblock copolymer). In vitro and in vivo anti-cancer effects of the preparations were evaluated to assess the use of the blending system as an optimal nanomedicine platform for insoluble anticancer agents.Results: The blending system (B20 system) with an optimized ratio of the triblock copolymers overcame the drawbacks of mono systems. Drug uptake from the drug-loaded B20 system and its anticancer effects against KB cells were superior compared to those of free drugs (doxorubicin hydrochloride and free paclitaxel). In particular, doxorubicin-loaded B20 resulted in extensive doxorubicin accumulation in tumor tissues and significantly higher in vivo anti-cancer effects compared to free doxorubicin.Conclusion: The blending system reported here could be a potential nanoplatform for drug delivery due to its simplicity and efficiency for pharmaceutical application.

Rapid SARA ATRP of Methyl Acrylate in Polyethylene Glycol Mediated by a Mixed Sulfite/CuBr2 Catalytic System

Supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP) of methyl acrylate was successfully performed in inexpensive, eco-friendly polyethylene glycol solvents and catalyzed by a mixed sulfite/CuBr2 system at room temperature. The presence of polyethylene glycol in the reaction mixtures allowed fast and controlled polymerizations throughout the whole reaction time. Remarkably, a fast polymerization can be achieved with a monomer conversion reaching 90% in only 50 min using PEG 200 as the reaction solvent. The controlled character of the ATRP of methyl acrylate was confirmed by the linear increase in molecular weight with monomer conversion, the narrow molecular weight distributions (Mw/Mn = 1.15) and the results of chain extension experiments. 1H NMR analysis also confirmed the molecular structure and chain-end functionality of the obtained polymers, and the effects of PEG molecular weight and inorganic sulfites on the polymerization behavior were investigated.

Influence of polyethylene glycol molecular weight on the anticancer drug delivery of pH‐sensitive polymeric micelle

ABSTRACTPolyethylene glycol (PEG) and pH‐sensitive polymers have been widely utilized in anticancer drug delivery systems due to their characteristics of prolonging circulation time and tumor‐responsive drug release. However, the effect of PEG molecular weight on the delivery of anticancer drug‐encapsulating pH‐sensitive polymer micelles has been poorly studied. Therefore, a simple method was used to prepare pH‐sensitive doxorubicin (DOX)‐loaded micelles (DOX/POD) based on polyethylene glycol‐2‐(octadecyloxy)‐1, 3‐dioxan‐5‐amine (POD) polymers, and the influence of PEG molecular weights (1 K, 2 K, and 5 K) on in vitro drug release and antitumor effect was further studied. Interestingly, as the molecular weight increased, the release amount of DOX was augmented. While the cytotoxicity and cellular uptake were increased, the molecular weight was decreased. It is reasonable to speculate that the high molecular weight of PEG may promote the dissolution rate of DOX, and their micelles with uncompact structure are being prone to disassembly in an acid environment. However, the low molecular weight of PEG may contribute to the formation of compact POD micelles, which make it easier to be uptaken by tumor cells resulting in the enhanced antitumor effect. Taken together, the results indicate that pH‐sensitive POD micelles with low molecular weight can achieve the efficient delivery of drugs, and PEG molecular weight in pH‐sensitive nanocarriers may influence the antitumor effect. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47854.

Environmental usefulness of PLA/PEG blends for controlled‐release systems of soil‐applied herbicides

ABSTRACTBlends consisting of biodegradable polylactide (PLA) and poly(ethylene glycol) (PEG) were investigated for their usefulness as an environmentally friendly herbicide formulation with prolonged activity. The aim of this study was to evaluate the release rate of selected soil‐applied herbicides from the PLA/PEG blend containing PEG of various molecular weights and to assess the phytotoxicity of the PEGs according to OECD 208 guidelines. The release rate of immobilized herbicides was correlated with degradation of the blends used. The progress of PLA/PEG blend degradation in water, soil, and activated sludge was estimated by sample weight loss, changes in blend composition, and microscopic observations of the blend surfaces during the experiment. The proposed formulation of the immobilized herbicide in a blend consisting of slowly biodegradable PLA and water‐soluble PEG provides the possibility to release the herbicides for a relatively long time, for approximately six months, which is a demand of weed management. The effect of PEGs on plant growth and development was dependent on both their concentration and molecular weight. With a higher concentration in soil and a higher molecular weight of PEG, a more harmful effect on plants was noticed. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47856.