PEGylated liposomes for diagnosis of polyethylene glycol allergy.

BACKGROUND: Polyethylene glycol (PEG) is a nonprotein polymer that is present in its native (unbound) form as an excipient in a range of products. It is increasingly being utilized clinically in the form of PEGylated liposomal medications and vaccines. PEG is the cause of anaphylaxis in a small percentage of drug reactions; however, diagnosis of PEG allergy is complicated by the variable and poor diagnostic performance of current skin testing protocols. OBJECTIVE: We assessed the diagnostic performance of PEGylated lipid medications as an alternative to currently described tests that use medications containing PEG excipients. METHODS: Nine patients with a strong history of PEG allergy were evaluated by skin testing with a panel of PEG-containing medications and with a PEGylated lipid nanoparticle vaccine (BNT162b2). Reactivity of basophils to unbound and liposomal PEG was assessed ex vivo, and specificity of basophil responses to PEGylated liposomes was investigated with a competitive inhibition assay. More detailed information is provided in this article's Methods section in the Online Repository available at www.jacionline.org. RESULTS: Despite compelling histories of anaphylaxis to PEG-containing medications, only 2 (22%) of 9 patients were skin test positive for purified PEG or their index reaction-indicated PEG-containing compound. Conversely, all 9 patients were skin test positive or basophil activation test positive to PEGylated liposomal BNT162b2 vaccine. Concordantly, PEGylated liposomal drugs (BNT162b2 vaccine and PEGylated liposomal doxorubicin), but not purified PEG2000, consistently induced basophil activation ex vivo in patients with PEG allergy but not in nonallergic controls. Basophil reactivity to PEGylated nanoparticles competitively inhibited by preincubation of basophils with native PEG2000. CONCLUSION: Presentation of PEG on the surface of a lipid nanoparticle increases its in vivo and ex vivo allergenicity, and improves diagnosis of PEG allergy.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.

GO-PEG Represses the Progression of Liver Inflammation via Regulating the M1/M2 Polarization of Kupffer Cells.

As a highly promising nanomaterial, exploring the impact of the liver, a vital organ, stands out as a crucial focus in the examination of its biological effects. Kupffer cells (KCs) are one of the first immune cells to contact with exotic-substances in liver. Therefore, this study investigates the immunomodulatory effects and mechanisms of polyethylene glycol-modified graphene oxide (GO-PEG) on KCs. Initial RNA-seq and KEGG pathway analyses reveal the inhibition of the TOLL-like receptor, TNF-α and NOD-like receptor pathways in continually stimulated KCs exposed to GO-PEG. Subsequent biological experiments validate that a 48-hour exposure to GO-PEG alleviates LPS-induced KCs immune activation, characterized by a shift in polarization from M1 to M2. The underlying mechanism involves the absorption of double-stranded RNA/single-stranded RNA, inhibiting the activation of TLR3 and TLR7 in KCs. Employing a Kupffer/AML12 cell co-culture model and animal studies, it is observed that GO-PEG indirectly inhibit oxidative stress, mitochondrial dysfunction, and apoptosis in AML12 cells, partially mitigating systemic inflammation and preserving liver tissue/function. This effect is attributed to the paracrine interaction between KCs and hepatocytes. These findings suggest a meaningful and effective strategy for treating liver inflammation, particularly when combined with anti-inflammatory drugs.

An Assay for Immunogenic Detection of Anti-PEG Antibody.

With the increasing use of polyethylene glycol (PEG) based proteins and drug delivery systems, anti-PEG antibodies have commonly been detected among the population, causing the accelerated blood clearance and hypersensitivity reactions, poses potential risks to the clinical efficacy and safety of PEGylated drugs. Therefore, vigilant monitoring of anti-PEG antibodies is crucial for both research and clinical guidance regarding PEGylated drugs. The enzyme-linked immunosorbent assay (ELISA) is a common method for detecting anti-PEG antibodies. However, diverse coating methods, blocking solutions and washing solutions have been employed across different studies, and unsuitable use of Tween 20 as the surfactant even caused biased results. In this study, we established the optimal substrate coating conditions, and investigated the influence of various surfactants and blocking solutions on the detection accuracy. The findings revealed that incorporating 1% bovine serum albumin into the serum dilution in the absence of surfactants will result the credible outcomes of anti-PEG antibody detection.

Towards understanding the crystallization of photosystem II: influence of poly(ethylene glycol) of various molecular sizes on the micelle formation of alkyl maltosides.

The influence of poly(ethylene glycol) (PEG) polymers H-(O-CH2-CH2)p-OH with different average molecular sizes p on the micelle formation of n-alkyl-ß-D-maltoside detergents with the number of carbon atoms in the alkyl chain ranging from 10 to 12 is investigated with the aim to learn more about the detergent behavior under conditions suitable for the crystallization of the photosynthetic pigment-protein complex photosystem II. PEG is shown to increase the critical micelle concentration (CMC) of all three detergents in the crystallization buffer in a way that the free energy of micelle formation increases linearly with the concentration of oxyethylene units (O-CH2-CH2) irrespective of the actual molecular weight of the polymer. The CMC shift is modeled by assuming for simplicity that it is dominated by the interaction between PEG and detergent monomers and is interpreted in terms of an increase of the transfer free energy of a methylene group of the alkyl chain by 0.2 kJ mol-1 per 1 mol L-1 increase of the concentration of oxyethylene units at 298 K. Implications of this effect for the solubilization and crystallization of protein-detergent complexes as well as detergent extraction from crystals are discussed.

Continuous Synthesis of a Macrocyclic Sulfite of Polyethylene Glycol by Cascaded Continuous Stirred Tank Reactors (CSTRs).

Many macrocyclic compounds are attractive drug-like molecules or intermediates due to their special properties. However, the bulk synthesis of such compounds are hindered by the necessity of using diluted solutions, in order to prevent intermolecular reactions that yields oligomer impurities, thereby resulting in a low production efficiency. Such challenge can be adequately addressed by using continuous reactors, allowing improved efficiency with smaller space footprints. In this work, we proposed a novel continuous process for the synthesis of a macrocyclic sulfite of tetraethylene glycol (PEG4-MCSi), which is a precursor to a very useful building block, PEG4-macrocyclic sulfate (PEG4-MCS). The basic reaction parameters, including stoichiometry and temperature, were first confirmed with small batch reactions, and the effectiveness of coiled reactors and continuous stirred tank reactors (CSTRs) were compared. Cascaded CSTRs were proven to be suitable, and the reaction parameters were subject to further optimization to give a robust continuous process. The process was then tested with 4 parallel runs for up to 64 h. Finally, the merits and demerits of batch and continuous reactions were also compared, demonstrating the suitability of latter in the bulk production of macrocyclic PEG-MCSi compounds.

Synthesis and Biological Evaluation of Methoxypolyethylene-Glycol-Substituted Abiraterone Derivatives as Potential Antiprostate Cancer Agents.

Globally, prostate cancer is the most commonly diagnosed tumor and a cause of death in older men. Abiraterone, an orally administered irreversible CYP17 inhibitor, is employed to treat prostate cancer. However, abiraterone has several clinical limitations, such as poor water solubility, low dissolution rate, low bioavailability, and toxic side effects in the liver and kidney. Therefore, there is a need to identify high-efficiency and low-toxicity water-soluble abiraterone derivatives. In this work, we aimed to design and synthesize a series of abiraterone derivatives by methoxypoly(ethylene glycol) (mPEG) modification. Their antitumor activities and toxicology were analyzed in vitro and in vivo. The most potent compound, 2e, retained the principle of action on the CYP17 enzyme target and significantly improved the abiraterone water solubility, cell permeability, and blood safety. No significant abnormalities were observed in toxicology. mPEG-modification significantly improved abiraterone's antitumor activity and efficiency while reducing the associated toxic effects. The finding will provide a theoretical basis for future clinical application of mPEG-modified abiraterone.

Physico-Chemical Properties of Laponite®/Polyethylene-oxide Based Composites.

This review aims to provide a literature overview as well as the authors' personal account to the studies of Laponite® (Lap)/Polyethylene-oxide (PEO) based composite materials and their applications. These composites can be prepared over a wide range of their mutual concentrations, they are highly water soluble, and have many useful physico-chemical properties. To the readers' convenience, the contents are subdivided into different sections, related with consideration of PEO properties and its solubility in water, behavior of Lap systems(structure of Lap-platelets, properties of aqueous dispersions of Lap and aging effects in them), analyzing ofproperties LAP/PEO systems, Lap platelets-PEO interactions, adsorption mechanisms, aging effects, aggregation and electrokinetic properties. The different applications of Lap/PEO composites are reviewed. These applications include Lap/PEO based electrolytes for lithium polymer batteries, electrospun nanofibers, environmental, biomedical and biotechnology engineering. Both Lap and PEO are highly biocompatible with living systems and they are non-toxic, non-yellowing, and non-inflammable. Medical applications of Lap/PEO composites in bio-sensing, tissue engineering, drug delivery, cell proliferation, and wound dressings are also discussed.

A post hoc analysis of PROTECT VIII kids assessing long-term efficacy and safety of damoctocog alfa pegol in adolescents with severe haemophilia A.

INTRODUCTION: The safety and efficacy of the extended half-life factor VIII (FVIII) product damoctocog alfa pegol (BAY 94-9027, Jivi®) has been demonstrated in the PROTECT VIII Kids study (NCT01775618), where male previously-treated patients (PTPs) aged <12 years old with severe haemophilia A and ≥ 50 exposure days (EDs) were treated prophylactically. The PROTECT VIII Kids extension study assessed the long-term safety and efficacy of damoctocog alfa pegol in the same population. AIM: To evaluate the long-term impact of damoctocog alfa pegol in a post hoc subgroup analysis of adolescent patients in the PROTECT VIII Kids study and its extension from 12th birthday onwards. METHODS: The current analysis included PTPs aged ≥12 years old, who remained in the extension for ≥6 months following their 12th birthday. The observation period was defined as the time from 12th birthday to the end of the extension period; all data from this birthday were included whether in the main study or extension phase. The main efficacy variable was annualised bleeding rate (ABR) and the main safety variable was the frequency of inhibitor development. RESULTS: This subgroup analysis comprised 25 patients. Median observation time after 12th birthday was 3.2 years. Median total/joint/spontaneous ABRs in the observation period were 1.7/0.7/0.3, respectively. Safety findings were consistent with those reported for the overall study population; no confirmed FVIII inhibitors or anti-drug antibodies were reported. CONCLUSIONS: Damoctocog alfa pegol is efficacious with a favourable safety profile in adolescents with haemophilia A, supporting its long-term use in children and adolescents.

Comparison of the efficacy and tolerability of elobixibat plus sodium picosulfate with magnesium citrate and split-dose 2-L polyethylene glycol with ascorbic acid for bowel preparation before outpatient colonoscopy: a study protocol for the multicentre, randomised, controlled E-PLUS trial.

BACKGROUND: Sodium picosulfate (SP)/magnesium citrate (MC) and polyethylene glycol (PEG) plus ascorbic acid are recommended by Western guidelines as laxative solutions for bowel preparation. Clinically, SP/MC has a slower post-dose defaecation response than PEG and is perceived as less cleansing; therefore, it is not currently used for major bowel cancer screening preparation. The standard formulation for bowel preparation is PEG; however, a large dose is required, and it has a distinctive flavour that is considered unpleasant. SP/MC requires a small dose and ensures fluid intake because it is administered in another beverage. Therefore, clinical trials have shown that SP/MC is superior to PEG in terms of acceptability. We aim to compare the novel bowel cleansing method (test group) comprising SP/MC with elobixibat hydrate and the standard bowel cleansing method comprising PEG plus ascorbic acid (standard group) for patients preparing for outpatient colonoscopy. METHODS: This phase III, multicentre, single-blind, noninferiority, randomised, controlled, trial has not yet been completed. Patients aged 40-69 years will be included as participants. Patients with a history of abdominal or pelvic surgery, constipation, inflammatory bowel disease, or severe organ dysfunction will be excluded. The target number of research participants is 540 (standard group, 270 cases; test group, 270 cases). The primary endpoint is the degree of bowel cleansing (Boston Bowel Preparation Scale [BBPS] score ≥ 6). The secondary endpoints are patient acceptability, adverse events, polyp/adenoma detection rate, number of polyps/adenomas detected, degree of bowel cleansing according to the BBPS (BBPS score ≥ 8), degree of bowel cleansing according to the Aronchik scale, and bowel cleansing time. DISCUSSION: This trial aims to develop a "patient-first" colon cleansing regimen without the risk of inadequate bowel preparation by using both elobixibat hydrate and SP/MC. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT; no. s041210067; 9 September 2021; https://jrct.niph.go.jp/ ), protocol version 1.5 (May 1, 2023).

Prospective, randomized study comparing two different regimens of split-dose polyethylene glycol and their effect on endoscopic outcomes.

BACKGROUND: Different split regimens of polyethylene glycol are routinely used and no guidelines are available to select an optimal protocol of ingestion. This study aims to compare the efficacy and side effect profile of two different regimens of polyethylene glycol bowel preparation solution: PEG (3 + 1) vs. PEG (2 + 2). METHODS: 240 patients above the age of 18 years were included in the study between June 1st and November 31st, 2023. Patients were randomly assigned either to Group A, consisting of 115 patients receiving a 3 L of PEG the night before the colonoscopy, and 1 L the same morning of the procedure. Or to group B, where 125 patients ingested 2 L the night before the procedure, and the remaining 2 L the same morning. The cleansing efficacy was evaluated by the attending endoscopist using the Boston Bowel Preparation Scale, through a score assigned for each segment of the colon (0-3). Side effects, tolerability, and willingness to retake the same preparation were listed by an independent investigator using a questionnaire administered before the procedure. RESULTS: A higher percentage of patients had gastric fullness with the 3 + 1 vs. 2 + 2 preparation (58.3% vs. 31.2%; p <.001). A higher Boston bowel preparation score was seen in patients who took the 2 + 2 vs. 3 + 1 preparation (7.87 vs. 7.23). Using the 2 + 2 preparation was significantly associated with higher Boston bowel preparation scores vs. the 3 + 1 preparation (OR = 1.37, p =.001, 95% CI 1.14, 1.64). After adjustment over other variables (age, gender, comorbidities, previous abdominal surgeries, presence of adenoma, and time between last dose and colonoscopy), results remained the same (aOR = 1.34, p =.003, 95% CI 1.10, 1.62). CONCLUSION: While both (2 + 2) and (3 + 1) regimens of polyethylene glycol are a good choice for a successful colonoscopy, we recommend the use of (2 + 2) regimen for its superior efficacy in bowel cleansing.

Aggregation-Induced Emission (AIE) in Polymers: Effect of Polymer size on the Fluorescence of Low Molecular Weight PEG and PPG.

Aggregation-induced emission (AIE) is a fascinating phenomenon where specific molecules exhibit enhanced fluorescence upon aggregation. This unique property has revolutionized the design and development of new fluorescent materials for different applications, from biosensors and organic light-emitting diodes (OLEDs) to biomedical imaging and diagnostics. Researchers are creating sensitive and selective sensing platforms, opening new avenues in material science and engineering by harnessing the potential of AIE. To expand the knowledge in this field, this study explored the aggregation-induced emission (AIE) properties of two polymers, namely polyethylene glycol (PEG) and polypropylene glycol (PPG) of low molecular weight (MW) using fluorescence spectroscopy and absorbance (UV). PEG-300 and PPG-725 were the most fluorescent polymers at UV of the ten investigated. Interestingly, AIE did not correlate linearly with molecular weight (MW), and monobutyl ether substitution in PEG with a similar MW substantially altered its AIE. Furthermore, fluorescence precisely quantified low polymer concentrations in water, and non-aqueous solvents suppressed AIE, suggesting potential for AIE manipulation. These findings enhance our understanding of AIE in polymers, fostering the development of novel materials for applications such as biosensors.

Ultrasmall Single-Chain Nanoparticles Derived from Amphiphilic Alternating Copolymers.

The collapse or folding of an individual polymer chain into a nanoscale particle gives rise to single-chain nanoparticles (SCNPs), which share a soft nature with biological protein particles. The precise control of their properties, including morphology, internal structure, size, and deformability, are a long-standing and challenging pursuit. Herein, a new strategy based on amphiphilic alternating copolymers for producing SCNPs with ultrasmall size and uniform structure is presented. SCNPs are obtained by folding the designed alternating copolymer in N,N-dimethylformamide (DMF) and fixing it through a photocatalyzed cycloaddition reaction of anthracene units. Molecular dynamics simulation confirms the solvophilic outer corona and solvophobic inner core structure of SCNPs. Furthermore, by adjusting the length of PEG units, precise control over the mean size of SCNPs is achieved within the range of 2.8 to 3.9 nm. These findings highlight a new synthetic strategy that enables enhanced control over morphology and internal structure while achieving ultrasmall and uniform size for SCNPs.

Regulation of cellulase production via calcium signaling in Trichoderma reesei under PEG8000 stress.

In this study, the effect of polyethylene glycol 8000 (PEG8000) stress on cellulase biosynthesis in Trichoderma reesei CICC2626 via calcium signaling was investigated, and a plausible mechanism by which intracellular Ca2+ regulates the transcription of cellulase genes was proposed. The results indicated that the total cellulase (filter paper-hydrolyzing activity [FPase]), endoglucanase (carboxymethyl cellulase activity [CMCase]), and ß-glucosidase activities of the strain were 1.3-, 1.2-, and 1.3-fold higher than those of the control (no PEG8000 addition) at a final concentration of 1.5% (w/v) PEG8000. Moreover, the transcriptional levels of cellulase genes, protein concentrations, and biomass increased. With the synergistic use of commercial cellulase and T. reesei CICC2626 cellulase to hydrolyze alkali-pretreated rice straw, the released reducing sugar concentration reached 372.7 mg/g, and the cellulose content (22.7%, 0.32 g) was significantly lower than the initial content (62.5%, 1.88 g). Transcriptome data showed that 12 lignocellulose degradation-related genes were significantly upregulated in the presence of 1.5% PEG8000. Furthermore, the addition of Ca2+ inhibitors and deletion of crz1 (calcineurin-responsive zinc finger 1-encoding gene, which is related to the calcium signaling pathway) demonstrated that calcium signaling plays a dominant role in PEG8000-induced cellulase genes overexpression. These results revealed a link between PEG8000 induction and calcium signaling transduction in T. reesei CICC2626. Moreover, this study also provides a novel inducer for enhanced cellulase production. KEY POINTS: • Cellulase biosynthesis in Trichoderma reesei could be enhanced by PEG8000 • PEG8000 could induce a cytosolic Ca2+ burst in Trichoderma reesei • The activated calcium signaling was involved in cellulase biosynthesis.

Blastobotrys nigripullensis, a new yeast species isolated from a fungal outbreak on an ancient Roman shipwreck in the Netherlands.

A new species of the yeast genus Blastobotrys was discovered on ancient ship timbers in the Netherlands. The species had developed on the wood of a river barge dating to the Roman period. The growth occurred after the preservative polyethylene glycol (PEG 4000) was washed out of some of the timbers due to an undetected leak in the storage unit. Mycological analysis of various timber samples revealed the presence of Microascus melanosporus (predominant), Microascus paisii, a member of the Acremonium chrysogenum-clade, and a new Blastrobotrys species. The new species produced sporothrix-like conidiophores with clavate blastoconidia (3-7 × 1-3.5 µm) and was found to be osmotolerant, capable of growth on low water activity media like malt yeast 50% glucose agar (MY50G). In this article we formally describe and introduce Blastrobotrys nigripullensis (CBS 17879 T) based on its morphology, physiology and phylogenetic placement.

Peritoneal B Cells Play a Role in the Production of Anti-polyethylene Glycol (PEG) IgM against Intravenously Injected siRNA-PEGylated Liposome Complexes.

Polyethylene glycol (PEG)-modified (PEGylated) cationic liposomes are frequently used as delivery vehicles for small interfering RNA (siRNA)-based drugs because of their ability to encapsulate/complex with siRNA and prolong the circulation half-life in vivo. Nevertheless, we have reported that subsequent intravenous (IV) injections of siRNA complexed with PEGylated cationic liposomes (PLpx) induces the production of anti-PEG immunoglobulin M (IgM), which accelerates the blood clearance of subsequent doses of PLpx and other PEGylated products. In this study, it is interesting that splenectomy (removal of spleen) did not prevent anti-PEG IgM induction by IV injection of PLpx. This indicates that B cells other than the splenic version are involved in anti-PEG IgM production under these conditions. In vitro and in vivo studies have shown that peritoneal cells also secrete anti-PEG IgM in response to the administration of PLpx. Interleukin-6 (IL-6) is a glycoprotein that is secreted by peritoneal immune cells and has been detected in response to the in vivo administration of PLpx. These observations indicate that IV injection of PLpx stimulates the proliferation/differentiation of peritoneal PEG-specific B cells into plasma cells via IL-6 induction, which results in the production of anti-PEG IgM from the peritoneal cavity of mice. Our results suggest the mutual contribution of peritoneal B cells as a potent anti-PEG immune response against PLpx.

Folding molecular origami from ribosomal RNA.

Approximately 80 percent of the total RNA in cells is ribosomal RNA (rRNA), making it an abundant and inexpensive natural source of long, single-stranded nucleic acid, which could be used as raw material for the fabrication of molecular origami. In this study, we demonstrate efficient and robust construction of 2D and 3D origami nanostructures utilizing cellular rRNA as a scaffold and DNA oligonucleotide staples. We present calibrated protocols for the robust folding of contiguous shapes from one or two rRNA subunits that are efficient to allow folding using crude extracts of total RNA. We also show that RNA maintains stability within the folded structure. Lastly, we present a novel and comprehensive analysis and insights into the stability of RNA:DNA origami nanostructures and demonstrate their enhanced stability when coated with polylysine-polyethylene glycol in different temperatures, low Mg2+ concentrations, human serum, and in the presence of nucleases (DNase I or RNase H). Thus, laying the foundation for their potential implementation in emerging biomedical applications, where folding rRNA into stable structures outside and inside cells would be desired.

Ultra-high-performance liquid chromatography with tandem mass spectrometry method for cellular toxicity and pharmacokinetic study of PEG1K polymers.

Polyethylene glycol (PEG) is one of the most commonly used polymers in drug delivery systems. The investigation of the pharmacokinetic behavior of PEG is important for revealing the toxicity and efficiency of PEG-related Nano-drug delivery systems. A high through-put and selective ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method coupled with collision-induced dissociation (CID) in source technique was developed and validated to determine PEG1K polymers in cellular samples in this study. The countless precursor ions of PEG1K are dissociated in the source to generate numerous product ions which have different numbers of subunits. The transition of [M+H]+ precursor ions → product ions at m/z 177.1 (four subunits)→89.1 (two subunits) was selected to determine PEG1K due to its high sensitivity. The UHPLC-MS/MS method coupled with CID in the source showed good linearity over the range of 0.1-10 µg/mL. Intra-day and inter-day accuracies and precisions of the assay were all within ± 12.39%. The assay was successfully applied to a cellular pharmacokinetic study of PEG1K in human breast cancer cells. The cytotoxicity of PEG1K polymers was also studied and the results indicated that the cytotoxicity of PEG1K was not significant in the range of 5-1200 µg/mL.

Improved pharmacokinetics and enhanced efficacy of the vancomycin derivative FU002 using a liposomal nanocarrier.

Antibiotic resistance still represents a global health concern which diminishes the pool of effective antibiotics. With the vancomycin derivative FU002, we recently reported a highly potent substance active against Gram-positive bacteria with the potential to overcome vancomycin resistance. However, the translation of its excellent antimicrobial activity into clinical efficiency could be hampered by its rapid elimination from the blood stream. To improve its pharmacokinetics, we encapsulated FU002 in PEGylated liposomes. For PEG-liposomal FU002, no relevant cytotoxicity on liver, kidney and red blood cells was observed. Studies in Wistar rats revealed a significantly prolonged blood circulation of the liposomal antibiotic. In microdilution assays it could be demonstrated that encapsulation does not diminish the antimicrobial activity against staphylococci and enterococci. Highlighting its great potency, liposomal FU002 exhibited a superior therapeutic efficacy when compared to the free form in a Galleria mellonella larvae infection model.

A bi-functional nanofibrous composite membrane for wound healing applications.

Various wound dressings have been developed so far for wound healing, but most of them are ineffective in properly reestablishing the skin's structure, which increases infection risks and dehydration. Electrospun membranes are particularly interesting for wound dressing applications because they mimic the extracellular matrix of healthy skin. In this study, a potential wound healing platform capable of inducing synergistic antibacterial and antioxidation activities was developed by incorporating bio-active rosmarinic acid-hydroxyapatite hybrid (HAP-RA) with different contents (0.5, 1, and 1.5 wt.%) into the electrospun polyamide 6 (PA6) nanofibers. Then, polyethylene glycol (PEG) was introduced to the nanofibrous composite to improve the biocompatibility and biodegradability of the dressing. The results indicated that the hydrophilicity, water uptake, biodegradability, and mechanical properties of the obtained PA6/PEG/HAP-RA nanofibrous composite enhanced at 1 wt.% of HAP-RA. The nanofibrous composite had excellent antibacterial activity. The antioxidation potential of the samples was assessed in vitro. The MTT assay performed on the L929 cell line confirmed the positive effects of the nanofibrous scaffold on cell viability and proliferation. According to the results, the PA6/PEG/HAP-RA nanofibrous composite showed the desirable physiochemical and biological properties besides antibacterial and antioxidative capabilities, making it a promising candidate for further studies in wound healing applications.