PEG Molecular Weight Research Articles

Preparation and characterization of biodegradable polyhydroxybutyrate-co-hydroxyvalerate/polyethylene glycol-based microspheres

The in vivo effectiveness of biomolecules may be limited by their rapid diffusion in the body and short half-life time. Encapsulation of these biomolecules allows protecting them against degradation and ensuring a controlled release over time. In this work, the production of polyhydroxybutyrate-co-hydroxyvalerate/polyethylene glycol-based microspheres loaded with heparin by double emulsion-solvent evaporation is investigated. Significant improvements are achieved after blending PHB-HV microspheres with PEG. First of all, an important decrease of the initial burst effect is ensured. Moreover, lower degradation of the microspheres is observed after 30days in the release medium. Finally, the release rate could be controlled using different PEG molecular weights and concentrations. A toxic effect of PHB-HV 30% PEG 1100gmol−1 microspheres is observed whereas PHB-HV and PHB-HV 30% PEG 10,000gmol−1 microspheres are not toxic. These microspheres seem to be most suited for further tissue engineering applications. The effectiveness of direct PEG blending to PHB-HV is proved, limiting the use of chemical reagents for PHB-HV/PEG copolymer synthesis and steps for chemical reagents removal from the copolymer.

Optimization of lipodisk properties by modification of the extent and density of the PEG corona

Lipodisks are nanosized flat, circular, phospholipid bilayers that are edge-stabilized by polyethylene glycol-conjugated lipids (PEG-lipids). Over the last decade, lipodisks stabilized with PEG of molecular weight 2000 or 5000 have been shown to hold high potential as both biomimetic membranes and drug carriers. In this study we investigate the possibilities to optimize the properties of the lipodisks, and widen their applicability, by reducing the PEG molecular weight and/or the density of the PEG corona.Results obtained by cryo-transmission electron microscopy and dynamic light scattering show that stable, well-defined lipodisks can be produced from mixtures of distearoylphosphatidylcholine (DSPC) and distearoylphosphatidylethanolamine conjugated to PEG of molecular weight 1000 (DSPE-PEG1000). Preparations based on the use of DSPE-PEG750 tend, in contrast, to be polydisperse in size and structure. By comparing immobilization of lipodisks stabilized with DSPE-PEG1000, DSPE-PEG2000, and DSPE-PEG5000 to porous and smooth silica surfaces, we show that the amount of surface bound disks can be considerably improved by the use of PEG-lipids with reduced molecular weight. Further, a modified preparation protocol that enables production of lipodisks with very low PEG-lipid content is described. The reduced PEG density, which facilitates the incorporation of externally added ligand-linked PEG-lipids, is shown to be beneficial for the production of targeting lipodisks.

Effect of molecular weight of PEG or PVA as reducing-stabilizing agent in the green synthesis of silver-nanoparticles

Silver nanoparticles (Ag-NPs) have been prepared by a green chemistry method using PEG or PVA, as reducing-stabilizing agent, and characterized using UV–vis, SEM-EDS, AFM and TEM. A comparative study was done to determine the PEG or PVA molecular weight (Mw) effect, on shape, size and dispersity of Ag-NPs. Lower Mw of PEG or PVA results in small Ag-NPs. The synthesized Ag-NPs were spherical with an average size of 2–30nm (PEG measured by TEM), and 2.5–45nm (PVA measured by TEM). Furthermore, photocatalytic degradation of Putnam sky-blue 39 was measured spectrophotometrically using Ag-NPs under sun light illumination, with 97% efficiency.

Choosing the dialyzer type in order to perform optimum hemodialysis in dogs

In order to identify the upper limits of the molecular size of chemicals to cross the chorion of zebrafish, Danio rerio, differently sized, non-toxic and chemically inert polyethylene glycols (PEGs; 2000–12,000 Da) were applied at concentrations (9.76 mM) high enough to provoke osmotic pressure. Whereas small PEGs were expected to be able to cross the chorion, restricted uptake of large PEGs was hypothesized to result in shrinkage of the chorion. Due to a slow, but gradual uptake of PEGs over time, molecular size-dependent equilibration in conjunction with a regain of the spherical chorion shape was observed. Thus, the size of molecules able to cross the chorion could be narrowed down precisely to ≤4000 Da, and the time-dependency of the movement across the chorion could be described. To account for associated alterations in embryonic development, fish embryo toxicity tests (FETs) according to OECD test guideline 236 (OECD, 2013) were performed with special emphasis to changes in chorion shape.FETs revealed clear-cut size-effects: the higher the actual molecular weight (= size) of the PEG, the more effects (both acutely toxic and sublethal) were found. No effects were seen with PEGs of 2000 and 3000 Da. In contrast, PEG 8000 and PEG 12,000 were found to be most toxic with LC50 values of 16.05 and 16.40 g/L, respectively. Likewise, the extent of chorion shrinkage due to increased osmotic pressure strictly depended on PEG molecular weight and duration of exposure. A reflux of water and PEG molecules into the chorion and a resulting re-shaping of the chorion could only be observed for eggs exposed to PEGs ≤4000 Da. Results clearly indicate a barrier function of the zebrafish chorion for molecules larger than 3000 to 4,000 Da.

Tuning the Selectivity of Dendron Micelles Through Variations of the Poly(ethylene glycol) Corona

Engineering controllable cellular interactions into nanoscale drug delivery systems is key to enable their full potential. Here, using folic acid (FA) as a model targeting ligand and dendron micelles (DM) as a nanoparticle (NP) platform, we present a comprehensive experimental and modeling investigation of the structural properties of DMs that govern the formation of controllable, FA-mediated cellular interactions. Our experimental results demonstrate that a high level of control over the specific cell interactions of FA-targeted DMs can be achieved through modulation of the PEG corona length and the FA content. Using various molecular weight PEGs (0.6K, 1K, and 2K g/mol) and contents of dendron-FA conjugate incorporated into DMs (0, 5, 10, 25 wt %), the cell interactions of the targeted DMs could be controlled to exhibit minimal to >25-fold enhancement over nontargeted DMs. Molecular dynamics simulations indicated that structural characteristics, such as solvent accessible surface area of FA, local PEG density near FA, and FA mobility, account in part for the experimental differences in cellular interactions. The molecular structure that allows FA to depart from the surface of DMs to facilitate the initial cell surface binding was revealed to be the most important contributor for determining FA-mediated cellular interactions of DMs. The modular properties of DMs in controlling their specific cell interactions support the potential of DMs as a delivery platform and offer design cues for future development of targeted NPs.

Synthesis and application of poly(ethylene glycol)-co-poly(β-amino ester) copolymers for small cell lung cancer gene therapy

The design of polymeric nanoparticles for gene therapy requires engineering of polymer structure to overcome multiple barriers, including prolonged colloidal stability during formulation and application. Poly(β-amino ester)s (PBAEs) have been shown effective as polymeric vectors for intracellular DNA delivery, but limited studies have focused on polymer modifications to enhance the stability of PBAE/DNA polyplexes. We developed block copolymers consisting of PBAE oligomer center units and poly(ethylene glycol) (PEG) end units. We fabricated a library of PEG-PBAE polyplexes by blending PEGylated PBAEs of different PEG molecular weights and non-PEGylated PBAEs of different structures at various mass ratios of cationic polymer to anionic DNA. Non-PEGylated PBAE polyplexes aggregated following a 24h incubation in acidic and physiological buffers, presenting a challenge for therapeutic use. In contrast, among 36 PEG-PBAE polyplex formulations evaluated, certain polyplexes maintained a small size under these conditions. These selected polyplexes were further evaluated for transfection in human small cell lung cancer cells (H446) in the presence of serum, and the best formulation transfected ∼40% of these hard-to-transfect cells while preventing polymer-mediated cytotoxicity. When PEG-PBAE polyplex delivered Herpes simplex virus thymidine kinase plasmid in combination with the prodrug ganciclovir, the polyplexes killed significantly more H446 cancer cells (35%) compared to healthy human lung fibroblasts (IMR-90) (15%). These findings indicate that PEG-PBAE polyplexes can maintain particle stability without compromising their therapeutic function for intracellular delivery to human small cell lung cancer cells, demonstrate potential cancer specificity, and have potential as safe materials for small cell lung cancer gene therapy. Statement of SignificanceMany natural and synthetic biomaterials have been investigated as non-viral vectors to deliver nucleic acids for cancer therapy. However, there are multiple hurdles to successful transfection including achieving particle stability, efficient delivery to cancer cells, and low cytotoxicity. In particular, engineering the physicochemical surface properties of a nanoparticle to improve stability is often offset by a decrease in the cellular entry and transfection efficiency. We developed stable polymeric nanoparticles that demonstrate high transfection efficiency by modifying synthetic biodegradable cationic polymers and engineering nanoparticle formulations using a combinatorial approach. The results of this study show the potential of biodegradable surface-modified polymeric nanoparticles as clinically translatable, biomaterial-based vehicles for cancer gene therapy.

Characterization of partitioning behaviors of immunoglobulin G in polymer-salt aqueous two-phase systems

The partitioning behavior of immunoglobulin G (IgG) in the aqueous two-phase system (ATPS) composed of poly(ethylene glycol) (PEG) and phosphate was studied. The parameters of ATPS exhibiting the pronounced effects on the partitioning behavior of IgG include phase composition, PEG molecular weight, and the addition of sodium chloride (NaCl). The accumulation of IgG at the interface of the ATPS increased drastically as the tie-line length (TLL) was increased. This trend was correlated with a linear relationship relating the natural logarithm of interfacial partition coefficient (ln G) to the difference of PEG concentration between the top phase and the bottom phase (Δ[PEG]), and a good fit was obtained. An attempt was made to correlate the natural logarithm of partition coefficient (ln K) to the presence of NaCl with the proposed linear relationship, ln K=α″ ln [Cl-]+β″. The proposed relationship, which serves as a better description of the underlying mechanics of the protein partitioning behavior in the polymer-salt ATPS, provides a good fit (r2>0.95) for the data of IgG partitioning. An optimum recovery of 99.97% was achieved in an ATPS (pH 7.5) composed of 14.0% (w/w) PEG 1450, 12.5% (w/w) phosphate and 5.0% (w/w) NaCl.

Nanoparticles coated with high molecular weight PEG penetrate mucus and provide uniform vaginal and colorectal distribution in vivo.

We previously reported that nanoparticles (NPs) coated with 10 kDa PEG were mucoadhesive. Here, we demonstrate that by increasing the surface density, PEG with molecular weight (MW) as high as 40 kDa can be used as a mucoinert NP surface coating. We compared two sets of reaction conditions for coating model polystyrene NPs with 10 kDa PEG and used optimized conditions to coat NPs with PEG as high as 40 kDa in MW. We then characterized NP transport in human cervicovaginal mucus ex vivo. We further administered PEG-coated NPs to the mouse cervicovaginal tract and colorectum to assess mucosal distribution in vivo. We demonstrate here that PEG with MW as high as 40 kDa can be densely grafted to the surface of NP to prevent interactions with mucus. NP coated with 10-40 kDa PEG rapidly diffused through human cervicovaginal mucus ex vivo, and uniformly lined the mouse colorectal and vaginal epithelium in vivo.

The effect of PEG molecular weights on the thermal stability and dissolution behaviors of griseofulvin-PEG crystalline inclusion complexes

Co-crystals formed between small molecular drugs and hydrophilic co-formers have shown great potential to optimize the dissolution profiles of drug substances. So far most of the co-formers used are small molecules. However, linear polymers are also able to form drug-polymer crystalline inclusion complexes (ICs). In contrast to the small molecular co-formers, molecular weight of the polymer co-formers can be easily changed without disrupting the IC crystal structure, and hence represents an interesting approach to tune the IC properties. In this study, we investigated the effect of PEG molecular weights on the thermal stability and dissolution behavior of Gris-PEG ICs. It was found that the thermal stability of Gris-PEG IC crystals first increased with PEG molecular weight, and then reached a plateau value, while an optimized PEG molecular weight existed for the dissolution profile. The experimental results were explained by the formation of two types of crystal defects during the IC growth in PEG melt: the void defects and the grain boundary defects. This is the first study on the pharmaceutical profiles of drug-polymer crystalline inclusion complexes.

Steric Pressure among Membrane-Bound Polymers Opposes Lipid Phase Separation.

Lipid rafts are thought to be key organizers of membrane-protein complexes in cells. Many proteins that interact with rafts have bulky polymeric components such as intrinsically disordered protein domains and polysaccharide chains. Therefore, understanding the interaction between membrane domains and membrane-bound polymers provides insights into the roles rafts play in cells. Multiple studies have demonstrated that high concentrations of membrane-bound polymeric domains create significant lateral steric pressure at membrane surfaces. Furthermore, our recent work has shown that lateral steric pressure at membrane surfaces opposes the assembly of membrane domains. Building on these findings, here we report that membrane-bound polymers are potent suppressors of membrane phase separation, which can destabilize lipid domains with substantially greater efficiency than globular domains such as membrane-bound proteins. Specifically, we created giant vesicles with a ternary lipid composition, which separated into coexisting liquid ordered and disordered phases. Lipids with saturated tails and poly(ethylene glycol) (PEG) chains conjugated to their head groups were included at increasing molar concentrations. When these lipids were sparse on the membrane surface they partitioned to the liquid ordered phase. However, as they became more concentrated, the fraction of GUVs that were phase-separated decreased dramatically, ultimately yielding a population of homogeneous membrane vesicles. Experiments and physical modeling using compositions of increasing PEG molecular weight and lipid miscibility phase transition temperature demonstrate that longer polymers are the most efficient suppressors of membrane phase separation when the energetic barrier to lipid mixing is low. In contrast, as the miscibility transition temperature increases, longer polymers are more readily driven out of domains by the increased steric pressure. Therefore, the concentration of shorter polymers required to suppress phase separation decreases relative to longer polymers. Collectively, our results demonstrate that crowded, membrane-bound polymers are highly efficient suppressors of phase separation and suggest that the ability of lipid domains to resist steric pressure depends on both their lipid composition and the size and concentration of the membrane-bound polymers they incorporate.

Versatile Supramolecular Gene Vector Based on Host–Guest Interaction

It is a great challenge to arrange multiple functional components into one gene vector system to overcome the extra- and intracellular obstacles for gene therapy. In this study, we developed a supramolecular approach for constructing a versatile gene delivery system composed of adamantyl-terminated functional polymers and a β-cyclodextrin based polymer. Adamantyl-functionalized low molecular weight PEIs (PEI-Ad) and PEG (Ad-PEG) as well as poly(β-cyclodextrin) (PCD) were synthesized by one-step chemical reactions. The supramolecular inclusion complex formed from PCD to assemble LMW PEI-Ad4 via host-guest interactions can condense plasmid DNA to form nanopolyplexes by electrostatic interactions. The supramolecular polyplexes can be further PEGylated with Ad-PEG to form inclusion complexes, which showed increased salt and serum stability. In vitro experiments revealed that these supramolecular assembly polyplexes had good cytocompatibility and showed high transfection activity close to that of the commercial ExGen 500 at high dose of DNA. Also, the supramolecular vector system exhibited about 60% silencing efficiency as a siRNA vector. Thus, a versatile effective supramolecular gene vector based on host-guest complexes was fabricated with good cytocompatbility and transfection activity.

Influence of the concentration and molecular weight of polyethylene glycol on the structure and permeability of polysulfone hollow fiber membranes

The influence of the concentration and molecular weight of polyethylene glycol (PEG, 400–40000 g mol–1) on the phase state and viscosity of ternary polysulfone–polyethylene glycol–N,N-dimethylacetamide solutions has been studied. It was shown that an increase in PEG molecular weight (MW) results in a decrease in the region of existence of homogeneous solutions on the phase diagram due to polymer incompatibility, and in an increase in the viscosity of polymer solutions. At a constant PEG concentration (5%) the viscosity depends on PEG MW in a complicated way: in the range of PEG molecular weights 1000–6000 g mol–1 the viscosity is nearly unchanged, but when the PEG MW exceeds 6000 g mol–1 a sharp increase in the viscosity of the polymer solutions is observed. It was shown that changes in the membrane performance are determined by PEG concentration in the dope solution. At a PEG concentration of 5% an increase in PEG MW results in an increase in membrane performance and a decrease in the rejection capability; at an increase in PEG concentration in the dope solution up to 25% the maximum pure water flux was observed for PEG-400. The bubble point test showed that with an increase in PEG molecular weight a fraction of large pores, which can be considered as selective layer defects, increases.

Synthesis and in vitro evaluation of pH-sensitive PEG-I-dC16 block polymer micelles for anticancer drug delivery.

To develop an acid trigger release of antitumour drug delivery carriers, pH-sensitive amphiphilic poly (ethyleneglycol)-imine-benzoic-dipalmitate (PEG-I-dC16 ) polymers were designed and synthesized and the drug-loaded micelles were evaluated in vitro. PEG-I-dC16 synthesized by Schiff base synthetic method and characterized by (1) H-NMR. To determine the drug-loading capacity, doxorubicin (DOX) was encapsulated in the micelles using membrane dialysis method. Zeta potential, particle size, drug-loading capacity, in vitro drug release in different pH conditions and cytotoxicity evaluation of micelles were carried out comparing with non-acid liable PEG-amide-benzoic-dipalmitate (PEG-A-dC16) polymers micelles. The cellular uptake and intracellular distribution of DOX were detected by flow cytometry and confocal laser scanning microscope. Drug-loading capacity and encapsulation efficiency of micelle (PEG molecular weight 2k) were 12.7 ± 1.1% and 49.8 ± 2.2%, respectively. The average particle size was 72.3 ± 2.5 nm. The DOX release rate of PEG-I-dC16 micelles is much higher at pH 6.5 than at pH 7.4. DOX cellular uptake and nuclear accumulation of PEG-I-dC16 micelles were more efficiency than that of PEG-A-dC16 micelles. The pH-sensitive PEG-I-dC16 micelles could be a promising drug delivery system for anticancer drugs.

Alginate/PEG based microcarriers with cleavable crosslinkage for expansion and non-invasive harvest of human umbilical cord blood mesenchymal stem cells

Porous microcarriers are increasingly used to expand and harvest stem cells. Generally, the cells are harvested via proteolytic enzyme treatment, which always leads to damages to stem cells. To address this disadvantage, a series of alginate/PEG (AL/PEG) semi-interpenetrating network microcarriers are prepared in this study. In this AL/PEG system, the chemically cross-linked alginate networks are formed via the reaction between carboxylic acid group of alginate and di-terminated amine groups of cystamine. PEG is introduced to modulate the degradation of microcarriers, which does not participate in this cross-linked reaction, while it interpenetrates in alginate network via physical interactions. In addition, chitosan are coated on the surface of AL/PEG to improve the mechanical strength via the electrostatic interactions. Biocompatible fibronectin are also coated on these microcarriers to modulate the biological behaviors of cells seeded in microcarriers. Results suggest that the size of AL/PEG microcarriers can be modulated via adjusting the contents and molecular weight of PEG. Moreover, the microcarriers are designed to be degraded with cleavage of disulfide crosslinkage. By changing the type and concentration of reductant, the ratio of AL to PEG, and the magnitude of chitosan coating, the degradation ability of AL/PEG microcarriers can be well controlled. In addition, AL/PEG microcarriers can support the attachment and proliferation of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs). More importantly, the expanded hUCB-MSCs can be detached from microcarriers after addition of reductant, which indeed reduce the cell damage caused by proteolytic enzyme treatment. Therefore, it is convinced that AL/PEG based microcarriers will be a promising candidate for large-scale expansion of hUCB-MSCs.

Single-step purification of ovalbumin from egg white using aqueous biphasic systems

The ability of aqueous biphasic systems (ABS) composed of polyethylene glycols of different molecular weights (PEG 400, 600 and 1000) and buffered aqueous solutions of potassium citrate/citric acid (pH 5.0–8.0) to selectively extract ovalbumin from egg white was here investigated. Phase diagrams, tie-lines and tie-line lengths were determined at 25°C and the partitioning of ovalbumin in these systems was then evaluated. Aiming at optimizing the selective extraction of ovalbumin in the studied ABS, factors such as pH, PEG molecular weight and amount of the phase-forming components were initially investigated with pure commercial ovalbumin. In all ABS, it was observed a preferential partitioning of ovalbumin to the polymer-rich phase, with extraction efficiencies higher than 90%. The best ABS were then applied in the purification of ovalbumin from the real egg white matrix. In order to ascertain on the ovalbumin purity and yield, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and size exclusion high performance liquid chromatography (SE-HPLC) analyses were conducted, confirming that the isolation/purification of ovalbumin from egg white was completely achieved in a single-step with a recovery yield of 65%. The results obtained show that polymer-salt-based ABS allow the selective extraction of ovalbumin from egg white with a simpler approach and better performance than previously reported. Finally, it is shown that ovalbumin can be completely recovered from the PEG-rich phase by an induced precipitation using an inexpensive and sustainable separation platform which can be easily applied on an industrial scale.

Effect of Surface Functionalization on the Cellular Uptake and Toxicity of Nanozeolite A.

Extensive use of zeolite nanoparticles in many areas, including medicine, has led to the concern about an impact and possible risk of their use for human health and the environment.In our studies, we investigated an uptake, retention, and cytotoxicity of nanozeolite A (BaA) functionalized with aminopropyl or poly(ethylene glycol) (PEG) of different chain lengths using human cervical carcinoma cell line. For internalization studies, nanozeolite was labeled with 133Ba radionuclide.The results show that in the case of PEG modification, toxicity and uptake depend on the PEG chain length. The highest toxicity has been observed for nanozeolites coated with short-length chain (Ba-silane-PEGm(MW350). Also, amine-modified nanozeolites exhibited high toxicity, while nanozeolites coated with long PEG molecules, BaA-silane-PEGm(MW1000), and BaA-silane-PEGm(MW2000), as well as unmodified nanozeolite, seem to be nontoxic.In conclusion, this study shows that uptake, retention, and toxicity of nanozeolites coated with various length PEG molecules groups depend on the molecular weight of PEG.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-016-1334-8) contains supplementary material, which is available to authorized users.

Influence of polyethylene glycol (PEG) chain length on the thermal behavior of spin-coated thin films of biodegradable poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)/PEG blends

The influence of the polyethylene glycol (PEG, Mn = 400, 1500, and 3400) chain length on the miscibility and thermal properties of spin-coated films of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHx, HHx = 6.9 mol %)/PEG blends was elucidated by using differential scanning calorimetry (DSC) and temperature-dependent infrared (IR) spectroscopy. To extract more detailed information about the spectral variations induced by the temperature, 2D correlation spectroscopy was applied to the temperature-dependent IR spectra of PHBHx/PEG blends. It was found that PEG 400 was completely miscible with PHBHx while PEG 1500 and 3400 were only partially miscible, reflecting that PHBHx/PEG miscibility decreased with the increasing molecular weight of PEG. The amorphous band of carbonyl group of 70/30 PHBHx/PEG 400 blend is resolved into two bands at 1744 and 1754 cm−1 in the asynchronous spectrum, which is not observed in the corresponding asynchronous 2D correlation spectra of PHBHx and its blend with PEG 1500 and 3400. This observation suggests that we captured the possible existence of two different types of amorphous state in 70/30 PHBHx/PEG 400 blend and the band at 1744 cm−1 is related to the amorphous mixture of PHBHx and PEG 400. Furthermore, 2D correlation analysis and the normalized peak height trends demonstrate that PEG 400 disrupts the crystalline structure of PHBHx, indicating low molecular weight PEG 400 has a clear effect on the thermal properties of PHBHx as well as depressing its melting temperature.

Liquid–liquid equilibria, electrical conductivity, and refractive indices of Poly(ethylene glycol) + sodium sulfate + guanidine hydrochloride aqueous two-phase systems: Correlation and thermodynamic modeling

The initial recovery steps for recombinant protein were carried out using aqueous two-phase systems in the presence of guanidine hydrochloride. To investigate the phase behavior of such systems, equilibrium data was obtained for molecular weight fractions of PEG (3000 and 6000) + sodium sulfate (pH 7) + guanidine hydrochloride (5% and 10% mass) + water at 25 °C. Displacement of the binodal toward higher concentrations through an increase in guanidine hydrochloride concentration was clearly observed. A slightly larger two-phase was obtained as the PEG molecular weight increased from PEG 3000 to 6000. The experimental binodal data of the system was successfully correlated with Bleasdale equations (high R2 and low SE). The effects of molecular weight, guanidine hydrochloride concentration, tie-line length, and slope of tie-line on the partition behaviors of guanidine hydrochloride were examined at constant pH. The compositions of each aqueous phase were calculated using two thermodynamic models for the activity coefficient. The calculated results showed that the extended Pitzer and extended UNIQUAC models can predict the data in the quaternary system well. The fitted binary interaction parameters of the models were reported.

Feasibility of poly(ethylene glycol) derivatives as diagnostic drug carriers for tumor imaging

Poly(ethylene glycol) (PEG) is an artificial but biocompatible hydrophilic polymer that has been widely used in clinical products. To evaluate the feasibility of using PEG derivative itself as a tumor imaging carrier via an enhanced permeability and retention (EPR) effect, we prepared indium-111-labeled PEG (111In-DTPA-PEG) and indocyanine green (ICG)-labeled PEG (ICG-PEG) with PEG molecular weights of 5–40kDa and investigated their in vivo biodistribution in colon26 tumor-bearing mice. Thereafter, single-photon emission computed tomography (SPECT) and photoacoustic (PA) imaging studies were performed. The in vivo biodistribution studies demonstrated increased tumor uptake and a prolongation of circulation half-life as the molecular weight of PEG increased. Although the observed differences in in vivo biodistribution were dependent on the labeling method (111In or ICG), the tumor-to-normal tissue ratios were comparable. Because PEG-based probes with a molecular weight of 20kDa (PEG20) showed a preferable biodistribution (highest accumulation among tissues excised and relatively high tumor-to-blood ratios), an imaging study using 111In-DTPA-PEG20 and ICG-PEG20 was performed. Colon26 tumors inoculated in the right shoulder were clearly visualized by SPECT 24h after administration. Furthermore, PA imaging using ICG-PEG20 also detected tumor regions, and the detected PA signals increased in proportion with the injected dose. These results suggest that PEG derivatives (20kDa) serve as robust diagnostic drug carriers for tumor imaging.

Role of Osmolytes on the Thermodynamic and Aggregation Properties of an ELP-Drug Carrier

The intracellular environment is crowded by biomolecules that occupy 40% of cell volume and generates a large excluded volume that perturbs the macromolecular environment. Here we investigate the role of organic osmolytes (TMAO, Betaine, Arginine and PEG) on the stability of a protein-drug carrier ELP, an engineered pentapeptide repeat comprised of [VPG(V5G3A2)G]150. To investigate the impact of steric crowding on ELP aggregation, we are measuring the dependence of ELP and Doxorubicin labeled-ELP solubility on inert solutes, osmolytes and serum proteins. Here we show that the phase change accompanying ELP aggregation is NaCl concentration dependent, and is due to an increased surface tension and decreased ELP solubility. The slope showing a linear decrease of ELP's TT with increasing salt concentration can be fitted to a linear equation T=T0+c[M] (Cho Younhee et al., 2008) with T0 being the TT of ELP in the absence of salt and the slope c showing the dependence of surface tension on salt concentration. We show that TMAO and Betaine preferentially hydrate the ELP out of solution as the ELP's TT linearly decreases with increasing osmolyte concentrations. Thus Betaine and TMAO alter ELP solubility without altering ELP structure (as measured by CD). In contrast, Arginine preferentially interacts with the ELP and suppresses aggregation by increasing its TT and solubility in solution. Finally, using different molecular weights PEG we show that inert additives enhance ELP aggregation consistent with an excluded volume effect. These results show that ELP aggregation is driven by solvent interactions and that changes in the solvent environment upon addition of different osmolytes enhance or diminish the aggregation of ELP. Future experiments will look at serum and serum proteins (BSA, HSA, IgG) to understand the impact of physiological solutions on ELP delivery.