Hydrophilic Poly Ethylene Glycol Research Articles

A biotin-modified and H2O2-activatable theranostic nanoplatform for enhanced photothermal and chemical combination cancer therapy

Although synergistic effects of photothermal therapy (PTT) and chemotherapy for cancer have been extensively investigated in previous studies, more potential strategies need to be exploited to alleviate severe adverse effects. In this study, a biotin-modified and activatable nanotheranostic system is developed. This system (BPSP/DOX-CyBA) composed of H2O2-sensitive thioketal (TK) linker, hydrophilic biotin-decorated polyethylene glycol (PEG) segment, hydrophobic polycaprolactone (PCL) segment, could self-assemble into (99 ± 1.3) nm nanoparticles and co-deliver H2O2-triggered photosensitizer CyBA and cytotoxic drugs DOX to tumor site. In vitro, DOX and CyBA could release rapidly from nanoparticles, CyBA accumulation in the mitochondria causes mitochondrial damage, leading to mitochondrial dysfunctions,while rising the level of ROS in B16F10 cells, and further to promote the micells to trigger release. CyBA could be activated into CyOH and the photothermal therapy was turn “off” into “on”. In BPSP/DOX-CyBA group, the local temperature within tumor reached 50 °C and cell apoptosis rate reached 68.6% under Laser irradiation (650 nm, 1 W/cm2). Fluorescence microscopy and flow cytometry analysis further demonstrated the better uptake efficiency on B16F10 cells with biotin decoration. In a mice B16F10 tumor model, the group with co-delivery CyBA and DOX had the best tumor retention effect, the maximal local temperature increasement and the minimum tumor growth with negligible side effects, suggesting the potential of BPSP/DOX-CyBA nanopalteform that synergistic photothermal therapy and chemotherapy and mitochondria damage as an effective melanoma treatment strategy.

Fabrication of a Modified Polyethersulfone Membrane with Anti-Fouling and Self-Cleaning Properties from SiO2-g-PHEMA NPs for Application in Oil/Water Separation

To prepare anti-fouling and self-cleaning membrane material, a physical blending modification combined with surface grafting modification has been carried out; first, poly (2-hydroxyethyl methacrylate) grafted silica nanoparticles (SiO2-g-PHEMA NPs) were synthesized using surface-initiated activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and used as a blending modifier to fabricate a polyethersulfone (PES)/SiO2-g-PHEMA organic–inorganic membrane by the phase-inversion method. During the membrane formation process, hydrophobic PES segments coagulated immediately to form a membrane matrix, and the hydrophilic SiO2-g-PHEMA NPs migrated spontaneously to the membrane surface in order to reduce interfacial energy, which enhanced the hydrophilicity and anti-fouling properties of the PES/SiO2-g-PHEMA membrane. Importantly, the membrane surface contained abundant PHEMA segments, which provided active sites for further surface functionalization. Subsequently, the carboxyl-terminated fluorocarbon surfactant (fPEG-COOH) composed of hydrophilic polyethyleneglycol segments and low-surface-energy perfluorinated alkyl segments was synthesized via the esterification of fPEG with succinic anhydride. Lastly, the PES/SiO2-g-PHEMA/fPEG membrane was prepared by grafting fPEG-COOH onto surface of the PES/SiO2-g-PHEMA. Thus, a versatile membrane surface with both fouling-resistant and fouling-release properties was acquired. The PES/SiO2-g-PHEMA/fPEG membrane has a large oil–water flux (239.93 L·m−2·h−1), almost 21 times that of PES blank membrane and 2.8 times of the PES/SiO2-g-PHEMA membrane. Compared with the unmodified PES membrane, the flux recovery ratio increased from 45.75% to 90.52%, while the total flux decline ratio decreased drastically from 82.70% to 13.79%, exhibiting outstanding anti-fouling and self-cleaning properties. Moreover, the grafted fPEG segments on the membrane surface show excellent stability due to the presence of stable chemical bonds. The grafted segments remain at the surface of the membrane even after a long shaking treatment. This suggests that this PES/SiO2-g-PHEMA/fPEG membrane material has potential for application in oil/water separation.

Extent of Internal Hydration influence the Activation of GPCR Rhodopsin

Rhodopsin is an archetypical GPCR responsible for dim‐light vision, which adopts a dynamic equilibrium between two metastable intermediates, metarhodopsin‐I (MI) and metarhodopsin‐II (MII), upon absorption of light. MI is an inactive conformational state of this GPCR, while MII is a fully active conformational state. We hypothesized that the MI to MII transition following isomerization of the retinal ligand involves a flood of bulk water into the protein core. To observe this change in the hydration level of the receptor during activation that is typically invisible to structural techniques such as X‐ray crystallography or cryo‐EM, we carried out a set of experiments using an osmotic stress approach. In this approach, the hydration level of rhodopsin was changed by placing the protein in native disk membranes in solutions with varying levels of osmotic pressure. Inert hydrophilic polyethylene glycol (PEG) solutes with different molecular weights and concentrations were used as the osmolytes. The effect of osmotic pressure on conformational dynamics was then quantified by measuring the reversible shifting of the metarhodopsin equilibrium using UV‐Visible spectroscopy. Results from these experiments show an influx of 80–100 water molecules into the rhodopsin interior, forming a partially disordered, solvent‐swollen active MII conformational state during photoactivation, a result supported by atomistic molecular dynamics simulations work [1, 2]. Additionally, we observed that the size of the polymer osmolyte played an important role in the modulation of rhodopsin’s activation: large osmolytes (PEG > 600) back shift the equilibrium to inactive MI state, while small osmolytes (PEG < 600) forward‐shift the equilibrium to MII state. We attribute this size dependence to the degree of osmolyte penetration into the rhodopsin core. Large polymers behave similarly to ideal osmolytes and dehydrate rhodopsin, while smaller polymers wriggle into the rhodopsin interior and stabilize the open MII conformation. These results necessitate a new understanding of GPCR activation in which the hydration level of protein is paramount in governing conformational energy landscapes. [1] U. Chawla et al. (2021) Angew. Chem. Int. Ed. 60, 2288–2295. [2] N. Leioatts et al. (2014) Biochemistry 53, 376−385.

Nanoparticles with dense poly(ethylene glycol) coatings with near neutral charge are maximally transported across lymphatics and to the lymph nodes

Lymphatic vessels have recently been shown to effectively deliver immune modulatory therapies to the lymph nodes, which enhances their therapeutic efficacy. Prior work has shown that lymphatics transport 10–250 nm nanoparticles from peripheral tissues to the lymph node. However, the surface chemistry required to maximize this transport is poorly understood. Here, we determined the effect of surface poly(ethylene glycol) (PEG) density and size on nanoparticle transport across lymphatic endothelial cells (LECs) by differentially PEGylated model polystyrene nanoparticles. Using an established in-vitro lymphatic transport model, we found PEGylation improved the transport of 100 and 40 nm nanoparticles across LECs 50-fold compared to the unmodified nanoparticles and that transport is maximized when the PEG is in a dense brush conformation or high grafting density (Rf/D = 4.9). We also determined that these trends are not size-dependent. PEGylating 40 nm nanoparticles improved transport efficiency across LECs 68-fold compared to unmodified nanoparticles. We also found that PEGylated 100 nm and 40 nm nanoparticles accumulate in lymph nodes within 4 h after intradermal injection, while unmodified nanoparticles accumulated minimally. Densely PEGylated nanoparticles traveled the furthest distance from the injection site and densely PEGylated 40 nm nanoparticles had maximum accumulation in the lymph nodes compared to low density PEGylated and unmodified nanoparticles. Finally, we determined that nanoparticles are transported via both paracellular and transcellular mechanisms, and that PEG conformation modulates the cellular transport mechanisms. Our results suggest that PEG conformation is crucial to maximize nanoparticle transport across LECs and into lymphatic vessels, making PEG density a crucial design. Optimizing PEG density on nanoparticle formulations has the potential to enhance immunotherapeutic and vaccine outcomes. Statement of significanceLymphatic vessels are an emerging target for drug delivery both in the context of modulating immune responses and enhancing bioavailability by avoiding first pass hepatic metabolism after oral delivery. Lymphatic vessels are the natural conduits from peripheral tissues to the lymph nodes, where the adaptive immune response is shaped, and eventually to systemic circulation via the thoracic duct. Lymphatics can be targeted via nanoparticles, but the surface chemistry required to maximize nanoparticle transport by lymphatics vessels remains poorly understood. Here, we demonstrate that coating nanoparticles with hydrophilic polyethylene glycol (PEG) effectively enhances their transport across lymphatic endothelial cells in vitro and in vivo and that both paracellular and micropinocytosis mechanisms underly this transport. We found that dense PEG coatings maximize lymphatic transport of nanoparticles, thus providing new material design criteria for lymphatic targeted drug delivery.

Stealth Liposomes (PEGylated) Containing an Anticancer Drug Camptothecin: In Vitro Characterization and In Vivo Pharmacokinetic and Tissue Distribution Study.

Numerous attempts to overcome the poor water solubility of cam ptothecin (CPT) by various nano drug delivery systems are described in various sources in the literature. However, the results of these approaches may be hampered by the incomplete separation of free CPT from the formulations, and this issue has not been investigated in detail. This study aimed to promote the solubility and continuous delivery of CPT by developing long-lasting liposomes using various weights (M.W. 2000 and 5000 Daltons) of the hydrophilic polymer polyethylene glycol (PEG). Conventional and PEGylated liposomes containing CPT were formulated via the lipid film hydration method (solvent evaporation) using a rotary flash evaporator after optimising various formulation parameters. The following physicochemical characteristics were investigated: surface morphology, particle size, encapsulation efficiency, in vitro release, and formulation stability. Different molecular weights of PEG were used to improve the encapsulation efficiency and particle size. The stealth liposomes prepared with PEG5000 were discrete in shape and with a higher encapsulation efficiency (83 ± 0.4%) and a prolonged rate of drug release (32.2% in 9 h) compared with conventional liposomes (64.8 ± 0.8% and 52.4%, respectively) and stealth liposomes containing PEG2000 (79.00 ± 0.4% and 45.3%, respectively). Furthermore, the stealth liposomes prepared with PEG5000 were highly stable at refrigeration temperature. Significant changes were observed using various pharmacokinetic parameters (mean residence time (MRT), half-life, elimination rate, volume of distribution, clearance, and area under the curve) of stealth liposomes containing PEG2000 and PEG5000 compared with conventional liposomes. The stealth liposomes prepared with PEG5000 showed promising results with a slow rate of release over a long period compared with conventional liposomes and liposomes prepared with PEG2000, with altered tissue distribution and pharmacokinetic parameters.

PH-redox responsive polymer-doxorubicin prodrug micelles studied by molecular dynamics, dissipative particle dynamics simulations and experiments

In this study, the ideal polymer materials were selected by molecular dynamics (MD) and dissipative particle dynamics (DPD) simulation methods, and pH and redox-sensitive micelles were prepared according to the simulation results. Through experiments, we successfully prepared hydrophilic block polyethylene glycol monomethyl ether (mPEG) connected hydrophobic block polylactic acid-glycolic acid (PLGA) amphiphilic polymer, and connected with redox fragment containing disulfide bond, and then connected with amide bond doxorubicin (DOX) to form mPEG-PLGA-SS-DOX prodrug, and further physical embedded free DOX. Finally, we obtained a particle size of 47.04 ± 0.103 nm, the potential of −23.8 ± 0.189 mV, Polymer dispersity index (PDI) of 0.231 ± 0.001, transmission electron microscopy (TEM) showed that it was spherical mPEG-PLGA-SS-DOX/DOX nanoparticles, its entrapment efficiency (EE) was 68.2%, loading content was 16.72%. The cumulative release of mPEG-PLGA-SS-DOX/DOX was 87.39% in a pH 5.0 and 10 mM Glutathione (GSH) tumor simulation environment. It was less toxic to normal cell HEK293 and more cytotoxic to HepG2 tumor cells. It showed that it was an excellent anti-tumor nano-drug. In addition, the application of computer simulation in the design of nanomedicine also provided a new research idea for the research of nanomedicine.

Significantly improved cell affinity of polydimethylsiloxane enabled by a surface-modified strategy with chemical coupling

Polydimethylsiloxane (PDMS) is a commonly used insulation/packaging material for implantable neural electrodes. Nevertheless, the PDMS-initiated tissue response would lead to the deterioration of the electrode performances post-implantation, owing to its intrinsic hydrophobic and cell-repellent surface. The conventional physical coatings by hydrophilic hydrogels or bioactive molecules are unable to maintain during the long-term implantation due to their low stability by physical adhesion. In this work, we first anchor both hydrophilic polyethylene glycol (PEG) and bioactive molecule poly-L-lysine (PLL) on the PDMS surface by chemical coupling to change the PDMS surface from hydrophobic and cell-repellent to hydrophilic and cell-adhesive. XPS tests indicate the chemically coupled modification layers are stable on the PDMS surface after experiencing a harsh rinse process. Contact angle measurements show that the use of PEG 600 with the moderate molecular weight results in the highest hydrophilicity for the resulting PDMS-PEG-PLL. PC12 cell evaluation results exhibit that the PDMS-PEG-PLL with PEG 600 leads to significantly larger cell adhesion area, more neurite number, and longer neurite length than the PDMS. The PDMS-PEG-PLL with PEG 600 featuring stable modification layers, high hydrophilicity, and superior cell affinity has great potential in stabilizing the neural electrode-tissue interface for the long-term implantation.Graphical abstract

Dendron-Polymer Hybrids as Tailorable Responsive Coronae of Single-Walled Carbon Nanotubes.

Functional composite materials that can change their spectral properties in response to external stimuli have a plethora of applications in fields ranging from sensors to biomedical imaging. One of the most promising types of materials used to design spectrally active composites are fluorescent single-walled carbon nanotubes (SWCNTs), noncovalently functionalized by synthetic amphiphilic polymers. These coated SWCNTs can exhibit modulations in their fluorescence spectra in response to interactions with target analytes. Hence, identifying new amphiphiles with interchangeable building blocks that can form individual coronae around the SWCNTs and can be tailored for a specific application is of great interest. This study presents highly modular amphiphilic polymer-dendron hybrids, composed of hydrophobic dendrons and hydrophilic polyethylene glycol (PEG) that can be synthesized with a high degree of structural freedom, for suspending SWCNTs in aqueous solution. Taking advantage of the high molecular precision of these PEG-dendrons, we show that precise differences in the chemical structure of the hydrophobic end groups of the dendrons can be used to control the interactions of the amphiphiles with the SWCNT surface. These interactions can be directly related to differences in the intrinsic near-infrared fluorescence emission of the various chiralities in a SWCNT sample. Utilizing the susceptibility of the PEG-dendrons toward enzymatic degradation, we demonstrate the ability to monitor enzymatic activity through changes in the SWCNT fluorescent signal. These findings pave the way for a rational design of functional SWCNTs, which can be used for optical sensing of enzymatic activity in the near-infrared spectral range.

Rapid synthesis of amphiphilic europium complexes via ultrasonic treatment-assisted crosslinking reaction

The fluorescent nanomaterials based on rare earth metal complexes have become one of the promising candidates for biomedical applications due to their unique optical properties. However, direct utilization of these rare earth complexes in biological systems is challengable for their poor water solubility. In this work, an ultrasonic treatment-assisted crosslinking reaction was developed for the first time to synthesize the fluorescent amphiphilic copolymers (named as Eu (TTA)3phen-HCCP-PEG), in which the hydrophobic europium complexes (Eu (TTA)3phen-NH2) and hydrophilic polyethylene glycol were conjugated together using hexachlorocyclotriphosphazene (HCCP) as crosslinking agent. The reaction could be occurred uner room temperature, mild reaction conditions without using catalysts. Owing to the amphiphilicity of Eu (TTA)3phen-HCCP-PEG, fluorescent nanoparticles can be formed in aqueous solution. Thereinto, the uptake behavior of Eu (TTA)3phen-HCCP-PEG by cells and cell toxicity testing were also utilized to evaluate their potential applications in biomedical fields. Results demonstrated that these fluorescent nanoparticles are of small size, high water dispersibility and low toxicity. The above results implied that Eu (TTA)3phen-HCCP-PEG could be potentially for biological imaging and imaging-guided drug delivery etc.

Inactivation of an Enveloped Virus by Immobilized Antimicrobial Peptides.

Infections caused by viruses are difficult to treat due to their life cycle, which depends on the replication machinery of the respective host cells. Commonly used antiviral strategies are based upon the application of, e.g., entry inhibitors and other compounds that interfere with virus replication. Besides possible side effects, the rapid occurrence of viral resistance poses a great challenge. Antimicrobial peptides (AMPs), as a component of the innate immunity, are able to kill bacteria and fungi and, in addition, may inactivate enveloped viruses. Many AMPs exert their biological function by impairing microbial and viral membranes. As a result, membrane integrity is lost, leading to bacterial killing and virus inactivation. Covalently immobilized AMPs have been shown to be biocidal too, which is of special interest when the presence of a soluble agent is to be avoided. Here, we demonstrate the conjugation of the human AMP LL37 to a solid support consisting of cellulose beads and its capability to inactivate murine cytomegalovirus as an example. Virus inactivation was highly reduced by several orders of magnitude when an appropriate coupling strategy was chosen. Coupling the AMP via a long and hydrophilic polyethylene glycol spacer proved to perform less effective compared to LL37 immobilization using a short cross-linker. In addition, it was found that LL37-conjugated beads did not induce hemolysis, a prerequisite for the development of blood contacting applications. Our findings may serve as a basis for the development of an implementable device that is able to reduce the viral load under real-life conditions.

Degradable smart composite foams for bone regeneration

Degradable scaffolds with high porosity, certain mechanical and shape memory properties and biocompatibility are ideal materials in the field of bone tissue engineering for minimally invasive surgical implantation methods. In this study, we prepared porous scaffolds using hydrophilic polyethylene glycol and degradable polycaprolactone as raw materials and calcium citrate/amorphous calcium phosphate as hybrid particles, via sequential gas foaming, salt leaching and freeze drying methods. The fabricated bone scaffold exhibited adjustable mechanical properties and pore structure, with high shape fixation (>94.5%) and shape recovery (>87%) in thermal cycling and excellent shape memory properties under simulated body fluid immersion near body temperature. Moreover, in cell proliferation and live/dead cell activity assay experiments, the scaffolds promoted the proliferation of mesenchymal stem cells (MSCs). Immunofluorescence staining assay experiments further showed that the scaffolds had strong expressions of human type Ⅰ collagen (Col I) and alkaline phosphatase (ALP) in bone matrix. The material is expected to be a potential alternative material for bone tissue engineering.

Evaluation of the stability of cucurbit[8]uril-based ternary host\u2212guest complexation in physiological environment and the fabrication of a supramolecular theranostic nanomedicine

BackgroundSupramolecular theranostics have exhibited promising potentials in disease diagnosis and therapy by taking advantages of the dynamic and reversible nature of non-covalent interactions. It is extremely important to figure out the stability of the driving forces in physiological environment for the preparation of theranostic systems.MethodsThe host−guest complexation between cucurbit[8]uril (CB[8]), 4,4′-bipyridinium, and napththyl guest was fully studied using various characterizations, including nuclear magnetic resonance spectroscopy, ultraviolet–visible (UV–vis) spectroscopy, isothermal titration calorimetry (ITC). The association constants of this ternary complex were determined using isothermal titration calorimetry. The stability of the non-covalent interactions and self-assemblies form from this molecular recognition was confirmed by UV–vis spectroscopy and dynamic light scattering (DLS). A supramolecular nanomedicine was constructed on the basis of this 1:1:1 ternary recognition, and its in vitro and in vivo anticancer efficacy were thoroughly evaluated. Positron emission tomography (PET) imaging was used to monitor the delivery and biodistribution of the supramolecular nanomedicine.ResultsVarious experiments confirmed that the ternary complexation between 4,4′-bipyridinium, and napththyl derivative and CB[8] was stable in physiological environment, including phosphate buffered solution and cell culture medium. Supramolecular nanomedicine (SNM@DOX) encapsulating a neutral anticancer drug (doxrubincin, DOX) was prepared based on this molecular recognition that linked the hydrophobic poly(ε-caprolactone) chain and hydrophilic polyethylene glycol segment. The non-covalent interactions guaranteed the stability of SNM@DOX during blood circulation and promoted its tumor accumulation by taking advantage of the enhanced permeability and retention effect, thus greatly improving the anti-tumor efficacy as compared with the free drug.ConclusionArising from the host-enhanced charge-transfer interactions, the CB[8]-based ternary recognition was stable enough in physiological environment, which was suitable for the fabrication of supramolecular nanotheranostics showing promising potentials in precise cancer diagnosis and therapy.Graphic

Comparison of pharmacokinetics and biodistribution of laser-synthesized plasmonic Au and TiN nanoparticles

Plasmonic nanostructures offer wide range of diagnostic and therapeutic functionalities for biomedical applications. Gold nanoparticles (Au NPs) present one of the most explored nanomaterial in this field, while titanium nitride nanoparticles (TiN NPs) is a new promising nanomaterial with superior plasmonic properties for biomedicine. However conventional chemical techniques for the synthesis of these nanomaterials cannot always match stringent requirements for toxicity levels and surface conditioning. Laser-synthesized Au and TiN NPs offer exceptional purity (no contamination by by-products or ligands) and unusual surface chemistry. Therefore, these NPs present a viable alternative to chemically synthesized counterparts. This work presents comparative analysis of pharmacokinetics and biodistribution of laser-synthesized 20 nm Au and TiN NPs under intravenous administration in mice model. Our data show that Au NPs and bare TiN NPs are rapidly eliminated from the blood circulation and accumulate preferentially in liver and spleen, while coating of TiN NPs by hydrophilic polymer polyethylene glycol (PEG) significantly prolongates blood circulation time and improves delivery of the NPs to tumor. We finally discuss potential applications of laser synthesized Au NPs in SERS, SEIRA and electrocatalysis, while TiN nanoparticles are considered as promising agents for photothermal therapy and photoacoustic imaging.

Facile synthesis of inorganic–organic hybrid fluorescent nanoparticles with AIE feature using hexachlorocyclotriphosphazene as the bridge

In recent 20 years, the functional materials with aggregation-induced emission (AIE) feature have shown huge superiority and great potential in biomedicine field and numerous strategies have been developed to fabricate these AIE-active functional materials. Though delightful developments, facile synthesis of inorganic–organic hybrid fluorescent nanoparticles with AIE feature has seldom reported thus far. In this work, we reported for the first time that novel cross-linked inorganic–organic hybrid polyphosphazene nanospheres with AIE feature could be simply synthesized via conjugation AIE-active fluorophore tetraphenylethylene derivative (TPE-NH2) with hydrophilic polyethylene glycol (PEG-NH2) using hexachlorocyclotriphosphazene (HCCP) as the bridge. This strategy is simple and high-efficient with some advantages (e.g., the reaction can occur under room temperature, the reaction time is short, no surfactant is required and no air-protection is needed). The structure, morphology and spectroscopic properties of TPE-HCCP-PEG nanoparticles (NPs) were characterized by various apparatus. To further evaluate their potential applications in biomedical fields, biocompatibility and cell uptake behavior of TPE-HCCP-PEG composites have been examined. Results demonstrated that TPE-HCCP-PEG NPs possessed intensive fluorescence and high water dispersibility and were of low cytotoxicity. These features endow TPE-HCCP-PEG NPs huge potential in fluorescence imaging. Also, the strategy can be extended for the construction of many other inorganic–organic hybrid polymers taken advantage of their unique features and convenient synthetic method. We expect that this work will open a new avenue for the synthesis of inorganic heterocycles centered AIE-active materials with extensive application prospects.

Rectal bioavailability of amoxicillin sodium in rabbits: Effects of suppository base and drug dose

In this paper, rectal absorption and tissue tolerance of amoxicillin sodium (AS) suppositories prepared in a hydrophilic base, polyethylene glycol (PEG) or lipophilic base, Suppocire® NA 15 (SNA 15), were investigated. Following in vitro characterization, including drug distribution in the suppository bases, drug-base interactions and drug release, pharmacokinetics were investigated in rabbits to determine absolute bioavailability (F) at two dose levels (100 mg and 200 mg). Both types of suppositories were found uniform in weight and content. Powder X-ray diffraction (XRD) and differential scanning calorimetry indicated that AS existed as solid dispersion or anhydrous crystalline dispersion in both suppositories at different ratios without changing melting points of the bases. This was supported by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy conjugated with energy dispersive X-ray (SEM/EDX). In dissolution medium, melting and spreading of SNA 15 and dissolution of PEG suppositories accounted for their different drug release kinetics and mean dissolution time (MDT). A rapid and complete amoxicillin absorption (F close to 100%) with a double peak pharmacokinetic profile was observed alongside minimal signs of tissue irritation in rabbits treated with SNA 15 suppositories at both dose levels. In contrast, the F of amoxicillin from PEG suppositories was 59%, increasing to 77.3% as AS dose doubled from 100 mg to 200 mg, reflected in the slower release predominately controlled by erosion of the base. An in vitro – in vivo correlation was observed (MDT vs F; p < 0.01). AS was stable in SNA 15 suppositories at least for three months at 20 ± 0.2 °C. This research highlighted the advantages of SNA 15 suppositories over the PEG suppositories in providing rapid and complete rectal absorption of AS and tissue compatibility.

Antifouling properties of amphiphilic poly(3-hydroxyalkanoate): an environmentally-friendly coating

The development of biofouling is a major problem for marine industries. The conception of antifouling and fouling release coatings, with controlled physical-chemical properties is a promising strategy. Among them, amphiphilic systems, such as those composed of a hydrophobic polydimethylsiloxane matrix and a hydrophilic polyethyleneglycol additive are the most efficient and up to date. Despite their effectiveness, these systems are questioned due to the petrochemical origin of PDMS. The aim of this project was to substitute the PDMS matrix with a biopolymer, poly(3-hydroxybuyrate-co-3-hydroxyvalerate) and to improve its anti-adhesion properties through the elaboration of an amphiphilic system, via the addition of PEG or PHBHHx-b-PEG copolymer. The results, including the physico-chemical properties of PHBHV based coatings and static adhesion tests on a marine bacterium, Bacillus 4J6 and a diatom, Phaeodactylum tricornutum are compared with those of PDMS and PEG-modified PDMS coatings. Real antiadhesion activity was obtained for the PHBHV/PHBHHx-b-PEG system for a promising eco-friendly strategy.

P-056. Profound changes in hemodynamics proving late-onset PE being of maternal origin

In this paper, rectal absorption and tissue tolerance of amoxicillin sodium (AS) suppositories prepared in a hydrophilic base, polyethylene glycol (PEG) or lipophilic base, Suppocire® NA 15 (SNA 15), were investigated. Following in vitro characterization, including drug distribution in the suppository bases, drug-base interactions and drug release, pharmacokinetics were investigated in rabbits to determine absolute bioavailability (F) at two dose levels (100 mg and 200 mg). Both types of suppositories were found uniform in weight and content. Powder X-ray diffraction (XRD) and differential scanning calorimetry indicated that AS existed as solid dispersion or anhydrous crystalline dispersion in both suppositories at different ratios without changing melting points of the bases. This was supported by Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy conjugated with energy dispersive X-ray (SEM/EDX). In dissolution medium, melting and spreading of SNA 15 and dissolution of PEG suppositories accounted for their different drug release kinetics and mean dissolution time (MDT). A rapid and complete amoxicillin absorption (F close to 100%) with a double peak pharmacokinetic profile was observed alongside minimal signs of tissue irritation in rabbits treated with SNA 15 suppositories at both dose levels. In contrast, the F of amoxicillin from PEG suppositories was 59%, increasing to 77.3% as AS dose doubled from 100 mg to 200 mg, reflected in the slower release predominately controlled by erosion of the base. An in vitro – in vivo correlation was observed (MDT vs F; p < 0.01). AS was stable in SNA 15 suppositories at least for three months at 20 ± 0.2 °C. This research highlighted the advantages of SNA 15 suppositories over the PEG suppositories in providing rapid and complete rectal absorption of AS and tissue compatibility.

Controlled self-release of ClO2 as an encapsulated antimicrobial agent for smart packaging

Facilitating the use of ClO2 gas in retail applications can improve the shelf life of produce and overcome the application limits of this gas. Moreover, the controlled release of ClO2 gas is desirable for preventing unwanted reactions. A novel controlled self-release material for ClO2 was developed, focusing on its applicability, convenience, and sustainability. Porous halloysite nanotubes (HNTs) were employed to encapsulate NaClO2 via an evacuation method. The HNT–NaClO2 was covered with hydrophilic polyethylene glycol to control the release behavior. Material characterizations confirm the success of the encapsulation and covering processes. Additionally, morphologies were observed to determine the inner and outer structures of the samples. Furthermore, the ClO2 release rates and applicability of the samples in packaging were investigated, indicating that sufficient gas in the packaging headspace can prolong the shelf life of cherry tomatoes. Therefore, this material can serve as an effective antimicrobial agent for packaging and agriculture products. Industrial relevanceThe retail application of ClO2 is limited, owing to its equipment requirements for on-set production (ClO2 generator), its safety (ClO2 is explosive at concentrations exceeding 10%), and its burst-release challenges. Therefore, the developed material with controlled release feature can be applied to various packaging purposes, in which minimal equipment and consumer safety are required.

Interfacial complexation of a neutral amphiphilic ‘tardigrade’ co-polymer with a cationic surfactant: Transition from synergy to competition

HypothesisNeutral amphiphilic PEG-g-PVAc co-polymer (a “tardigrade” polymer consisting of a hydrophilic polyethylene glycol, PEG, backbone with hydrophobic polyvinyl acetate, PVAc, grafts) can form complexes at the air–water interface with cationic dodecyltrimethylammonium bromide (DTAB) via self-assembly. Compared to anionic SDS, cationic DTAB headgroups are expected to interact strongly with the negatively charged OH– groups from the partial dissociation of the PVAc grafts. We anticipate a transition from synergistic to competitive behaviour, which is expected to be dependent on the surfactant structural characteristics and concentration. ExperimentsDTAB/PEG-g-PVAc mixtures were investigated using a combination of dynamic and equilibrium surface tension measurements, neutron reflectivity (NR) at the air–water interface, and foaming tests. We varied the concentrations of both the DTAB (0.05 to 5 critical micelle concentration, cmc) and that of PEG-g-PVAc (0.2 and 2 critical aggregation concentration, cac). FindingsOur results show that the interfacial interactions between DTAB and PEG-g-PVAc were both synergistic and antagonistic, depending sensitively on the surfactant concentration. At DTAB concentrations below its cmc, a pronounced cooperative adsorption behaviour was likely driven by the hydrophobic interactions between the DTAB tail and the PVAc grafts and the attraction between the DTAB headgroups and the partially dissociated –O- groups in the partially hydrolysed PVAc grafts, forming a mixed layer. This synergistic adsorption behaviour transitioned to a competitive adsorption behaviour at DTAB concentrations above its cmc, leading to polymer-surfactant partition, forming a “hanging” polymer layer underlying a surfactant monolayer at the interface. We postulate that DTAB/PEG-g-PVAc complexation in the bulk contributed to partial depletion of the mixture from the interface. We therefore consider this polymer/surfactant system to be a moderately interacting system at the air–water interface. No discernible differences in the foaming behaviour were observed between the DTAB/PEG-g-PVAc systems and the pure surfactant. Our results suggest that surfactant headgroup characteristics (particularly charges) were crucial in determining the structure and composition of polymer-surfactant complexes at the air–water interface, as well as the foamability and foam stability, whilst the coexistence of the synergistic and competitive adsorption behaviour is attributed to the unique architecture of the tardigrade polymer with amphiphilicity and partial charge, facilitating different surfactant-polymer interactions at different DTAB concentrations.

Hybrid inorganic-organic fluorescent silica nanoparticles—influence of dye binding modes on dye leaching

Silica nanoparticles with embedded fluorescent dyes represent an important class of markers for example in biological imaging. We systematically studied the various incorporation mechanisms of fluorescent xanthene dyes in 30–40 nm silica nanoparticles. An important parameter was the interaction of the dye with the matrix material, either by weak electrostatic or strong covalent interactions, which also has implications on the stability of fluorescence and brightness of the dyes. Factors that can influence leaching of dyes such as the position of the dyes in particles and the intensity of the particle-dye interaction were investigated by using the solvatochromic effect of xanthene dyes and by stationary fluorescence anisotropy measurements. We compared uranine and rhodamine B, which were physically embedded, with modified fluorescein isothiocyanate and rhodamine B isothiocyanate, which were covalently bound to the silica matrix within a usual Stöber synthesis. Systematic leaching studies of time spans up to 4 days revealed that covalent bonding of dyes like fluorescein isothiocyanate or rhodamine B isothiocyanate is necessary for fluorescence stability, since dyes bound by physical interaction tend to leach out of porous silica networks. Coverage of silica particles with hydrophobic protection layers of alkyltrialkoxysilanes or hydrophilic polyethylene glycol (PEG) groups resulted in a better retention of physisorbed dyes and provides the possibility to adapt the particles to the polarity of the medium. Best results were archived with PEG groups, but even small trimethylsilyl (TMS) groups already reduce leaching.