Evaluation of High-Performance Polyether Ether Ketone Polymer Treated with Piranha Solution and Epigallocatechin-3-Gallate Coating.

Background: Dental implantation has become a standard procedure with high success rates, relying on achieving osseointegration between the implant surface and surrounding bone tissue. Polyether ether ketone (PEEK) is a promising alternative to traditional dental implant materials like titanium, but its osseointegration capabilities are limited due to its hydrophobic nature and reduced surface roughness. Objective: The aim of the study is to increase the surface roughness and hydrophilicity of PEEK by treating the surface with piranha solution and then coating the surface with epigallocatechin-3-gallate (EGCG) by electrospraying technique. Materials and Methods: The study includes four groups intended to investigate the effect of piranha treatment and EGCG coating: a control group of PEEK discs with no treatment (C), PEEK samples treated with piranha solution (P), a group of PEEK samples coated with EGCG (E), and a group of PEEK samples treated with piranha solution and coated with EGCG (PE). Surface roughness, wettability, and microhardness were assessed through statistical analysis. Results: Piranha treatment increased surface roughness, while EGCG coating moderated it, resulting in an intermediate roughness in the PE group. EGCG significantly improved wettability, as indicated by the reduced contact angle. Microhardness increased by about 20% in EGCG-coated groups compared to noncoated groups. Statistical analysis confirmed significant differences between groups in all tests. Conclusion: This study demonstrates the potential of EGCG coating to enhance the surface properties of PEEK as dental implants. The combined piranha and EGCG modification approach shows promise for improved osseointegration, although further vivo research is necessary. Surface modification techniques hold the key to optimizing biomaterial performance, bridging the gap between laboratory findings and clinical implementation in dental implantology.

Label-Free Composition Analysis of Supramolecular Polymer-Nanoparticle Hydrogels by Reversed-Phase Liquid Chromatography Coupled with a Charged Aerosol Detector.

Supramolecular hydrogels formed through polymer-nanoparticle interactions are promising biocompatible materials for translational medicines. This class of hydrogels exhibits shear-thinning behavior and rapid recovery of mechanical properties, providing desirable attributes for formulating sprayable and injectable therapeutics. Characterization of hydrogel composition and loading of encapsulated drugs is critical to achieving the desired rheological behavior as well as tunable in vitro and in vivo payload release kinetics. However, quantitation of hydrogel composition is challenging due to material complexity, heterogeneity, high molecular weight, and the lack of chromophores. Here, we present a label-free approach to simultaneously determine hydrogel polymeric components and encapsulated payloads by coupling a reversed phase liquid chromatographic method with a charged aerosol detector (RPLC-CAD). The hydrogel studied consists of modified hydroxypropylmethylcellulose, self-assembled PEG-b-PLA nanoparticles, and a therapeutic compound, bimatoprost. The three components were resolved and quantitated using the RPLC-CAD method with a C4 stationary phase. The method demonstrated robust performance, applicability to alternative cargos (i.e., proteins) and was suitable for composition analysis as well as for evaluating in vitro release of cargos from the hydrogel. Moreover, this method can be used to monitor polymer degradation and material stability, which can be further elucidated by coupling the RPLC method with (1) a multi-angle light scattering detector (RPLC-MALS) or (2) high resolution mass spectrometry (RPLC-MS) and a Fourier-transform based deconvolution algorithm. We envision that this analytical strategy could be generalized to characterize critical quality attributes of other classes of supramolecular hydrogels, establish structure-property relationships, and provide rational design guidance in hydrogel drug product development.

Revolutionizing Knee Osteoarthritis Treatment: Innovative Self-Nano-Emulsifying Polyethylene Glycol Organogel of Curcumin for Effective Topical Delivery.

In the current study, self-nano-emulsifying (SNE) physically cross-linked polyethylene glycol (PEG) organogel (SNE-POG) as an innovative hybrid system was fabricated for topical delivery of water-insoluble and unstable bioactive compound curcumin (CUR). Response surface methodology (RSM) based on Optimal Design was utilized to evaluate the formulation factors. Solid fiber mechanism with homogenization was used to prepare formulations. Pharmaceutical evaluation including rheological and texture analysis, their mathematical correlations besides physical and chemical stability experiments, DSC study, in vitro release, skin permeation behavior, and clinical evaluation were carried out to characterize and optimize the SNE-OGs. PEG 4000 as the main organogelator, Poloxamer 188 (Plx188) and Ethyl Cellulose (EC) as co-gelator/nanoemulsifier agents, and PEG 400 and glycerin as solvent/co-emulsifier agents could generate SNE-POGs in PS range of 356 to 1410 nm that indicated organic base percentage and PEG 4000 were the most detrimental variables. The optimized OG maintained CUR stable in room and accelerated temperatures and could release CUR sustainably up to 72 h achieving high flux of CUR through guinea pig skin. A double-blind clinical trial confirmed that pain scores, stiffness, and difficulty with physical function were remarkably diminished at the end of 8 weeks compared to the placebo (71.68% vs. 7.03%, 62.40% vs. 21.44%, and 45.54% vs. 8.66%, respectively) indicating very high efficiency of system for treating knee osteoarthritis. SNE-POGs show great potential as a new topical drug delivery system for water-insoluble and unstable drugs like CUR that could offer a safe and effective alternative to conventional topical drug delivery system.

Conventional vs PEGylated loaded liposomal formulations by microfluidics for delivering hydrophilic chemotherapy.

Developing drug delivery systems (DDSs) is one of the approaches used to improve cancer treatment, with the main goal of loading cancer drugs into a carrier targeting a specific organ and avoiding the distribution to healthy tissues. Nanoparticles (NPs) have been shown to be one of the optimum carriers that can be used as DDSs. Lipid-based NPs, such as liposomes, have been investigated in the current study due to their low toxicity and ability to carry hydrophilic and hydrophobic molecules. In the current studies, conventional liposomes composed of DPPC, and cholesterol and PEGylated liposomes composed of DPPC, cholesterol, and DSPE-PEG2000 are manufactured and loaded with Carboplatin. The study focused on investigating and comparing the impact of modifying the carboplatin-loaded liposomes with different concentrations of DSPE-PEG2000 on the NP diameter, polydispersity, ζ-potential, encapsulation efficiency (EE%), and drug release. The hydrodynamic microfluidic system was used to investigate any possible improvement in the EE% over other conventional methods. The results showed the microfluidic system's promising effect in enhancing the EE% of the Carboplatin. Moreover, the results showed a smaller diameter and higher stability of the PEGylated liposome. However, conventional liposomes represent better homogeneity and higher encapsulation efficiency for hydrophilic molecules.

Influence of Different Ratios of DSPE-PEG2k on Ester Prodrug Self-Assembly Nanoparticles for Cell Migration and Proliferation Suppression.

Background: Bufalin (BFL, an active anti-tumor compound derived from toad venom) is limited in its application due to high toxicity and rapid metabolism of the cardiotonic steroid. Ester prodrug self-assembly nanoparticles have shown significant improved effects in addressing the above-mentioned issues. Methods: An ester bond was formed between linoleic acid and bufalin to synthesize linoleic acid-bufalin prodrug (LeB). The self-assembly nanoparticles (LeB-PSNs) containing different mass ratios of DSPE-PEG2k and prodrug (6:4, 7:3, 8:2, 9:1 and 10:0) were prepared via co-precipitation method and defined as 6:4-PSNs, 7:3-PSNs, 8:2-PSNs, 9:1-PSNs and LeB-PSNs, respectively. Further, the characterization (particle size, zeta potential, surface morphology and stability) of the nanoparticles was carried out. Finally, we evaluated the impact of different ratios of DSPE-PEG2k on the hydrolysis rate, cytotoxicity, cellular uptake, cell migration and proliferation suppression potential of the prodrug nanoparticles. Results: The linoleic acid-bufalin prodrug (LeB) was successfully synthesized. Upon the addition of DSPE-PEG2k at different weight ratios, both particle size and polydispersity index (PDI) significantly decreased, while the zeta potential increased remarkably. No significant differences in particle size, PDI and Zeta potential were observed among the 9:1, 8:2 and 7:3 PSNs. Notably, the 8:2 (w/w) DSPE-PEG2k nanoparticles exhibited superior stability, hydrolysis and cellular uptake rates, along with efficient cell cytotoxicity, cell migration and proliferation suppression. Conclusion: These findings indicate that DSPE-PEG2k could improve the performance of BFL prodrug nanoparticles, namely enhancing stability and achieving adaptive drug release by modulating the hydrolysis rate of esterase. This study therefore provides more opportunities for the development of BFL application.

Preparation and Evaluation of Folate Modified PEG-PLLA Nanoparticles Loaded with Lycorine for Glioma Treatment.

Lycorine is a kind of natural active ingredient with a strong antitumor effect. In this study, folate ligand-conjugated polyethylene glycol-block-poly(l-lactide) (PEG-PLLA) nanoparticles (FA-PEG-PLLA NPs) were designed to deliver lycorine to enhance its anti-glioma activity. The successful preparation of the FA-PEG-PLLA polymer was confirmed by 1H-NMR, FT-IR, XRD, TGA, and DSC. The optimal formulation for LYC@FA-PEG-PLLA NPs was determined by response surface analysis as follows: sodium dodecyl sulfate (SDS) of 1%, carrier material of 0.03 g, organic phase volume of 3 mL, and ultrasonic power of 20%. The LYC@FA-PEG-PLLA NPs exhibited an encapsulation efficiency of 83.58% and a particle size of 49.71 nm, demonstrating good stability. Hemolysis experiments, MTT assays, and cell scratch assays revealed excellent biocompatibility of FA-PEG-PLLA and superior anti-glioma activity of LYC@FA-PEG-PLLA NPs compared to the raw drug. Additionally, cell apoptosis assays, ROS experiments, and western blot analysis demonstrated that LYC@FA-PEG-PLLA NPs contributed to cell apoptosis by inducing ROS generation and increasing the expression of NF-κB inhibitory protein IκBα. These results suggested that LYC@FA-PEG-PLLA NPs hold promise for glioma treatment.

Hydrogen-bonded cytosine-endowed supramolecular polymeric nanogels: Highly efficient cancer cell targeting and enhanced therapeutic efficacy.

We demonstrate that cytosine moieties within physically cross-linked supramolecular polymers not only manipulate drug delivery and release, but also confer specific targeting of cancer cells to effectively enhance the safety and efficacy of chemotherapy-and thus hold significant potential as a new perspective for development of drug delivery systems. Herein, we successfully developed physically cross-linked supramolecular polymers (PECH-PEG-Cy) comprised of hydrogen-bonding cytosine pendant groups, hydrophilic poly(ethylene glycol) side chains, and a hydrophobic poly(epichlorohydrin) main chain. The polymers spontaneously self-assemble into a reversibly hydrogen-bonded network structure induced by cytosine and directly form spherical nanogels in aqueous solution. Nanogels with a high hydrogen-bond network density (i.e., a higher content of cytosine moieties) exhibit outstanding long-term structural stability in cell culture substrates containing serum, whereas nanogels with a relatively low hydrogen-bond network density cannot preserve their structural integrity. The nanogels also exhibit numerous unique physicochemical characteristics in aqueous solution, such as a desirable spherical size, high biocompatibility with normal and cancer cells, excellent drug encapsulation capacity, and controlled pH-responsive drug release properties. More importantly, in vitro experiments conclusively indicate the drug-loaded PECH-PEG-Cy nanogels can selectively induce cancer cell-specific apoptosis and cell death via cytosine receptor-mediated endocytosis, without significantly harming normal cells. In contrast, control drug-loaded PECH-PEG nanogels, which lack cytosine moieties in their structure, can only induce cell death in cancer cells through non-specific pathways, which significantly inhibits the induction of apoptosis. This work clearly demonstrates that the cytosine moieties in PECH-PEG-Cy nanogels confer selective affinity for the surface of cancer cells, which enhances their targeted cellular uptake, cytotoxicity, and subsequent induction of programmed cell death in cancer cells.

Freezing-mediated formation of supraproteins using depletion forces.

Hypothesis Long-acting formulations such as microparticles, injectable depots and implantable devices can realize spatiotemporally controlled delivery of protein drugs to extend their therapeutic in vivo half-lives. To efficiently encapsulate the protein drugs into such drug delivery systems, (sub)micron-sized protein particles are needed. The formation of micronized supraproteins can be induced through the synergistic combination of attractive depletion forces and freezing. The size of the supraproteins can be fine-tuned from submicron to several microns by adjusting the ice crystallization rate through the freeze-quench depth, which is set by the target temperature. Methods Supraprotein micron structures were prepared from protein solutions under various conditions in the presence and absence of nonadsorbing polyethylene glycol. Scanning electron microscopy and dynamic light scattering were employed to determine the sizes of the supraproteins and real-time total internal reflection fluorescent microscopy was used to follow the supraprotein formation during freezing. The protein secondary structure was measured before and after micronization by circular dichroism. A phase diagram of a protein-polyethylene glycol mixture was theoretically predicted to investigate whether the depletion interaction can elucidate the phase behavior. Findings Micronized protein supraparticles could be prepared in a controlled manner by rapid freeze-drying of aqueous mixtures of bovine serum albumin, horseradish peroxidase and lysozyme mixed with polyethylene glycol. Upon freezing, the temperature quench initiates a phase separation process which is reminiscent of spinodal decomposition. This demixing is subsequently arrested during droplet phase separation to form protein-rich microstructures. The final size of the generated protein microparticles is determined by a competition between phase separation and cooling rate, which can be controlled by target temperature. The experimental phase diagram of the aqueous protein-polyethylene glycol dispersion aligns with predictions from depletion theory for charged colloids and nonadsorbing polymers.

Development of lactic acid based chain extender and soybean oil-derived polyurethanes for ecofriendly sustained drug delivery systems.

In the present study, a range of sustainable, biocompatible and biodegradable polyurethanes (PU-1 to PU-4) were synthesized using different combinations of biobased polyol (obtained through the epoxidation of soybean oil, followed by ring opening with ethanol) and polyethylene glycol (PEG) and isophorone diisocyanate. The sustainable chain extender used in this study was synthesized by the esterification of lactic acid with ethylene glycol (EG). The synthesized PU samples were characterized through scanning electron microscopy (SEM), Fourier transformed infrared (FTIR) and nuclear magnetic resonance (1H NMR and 13C NMR) spectroscopy. Wetting ability and thermal degradation analysis (TGA) of the samples were also studied. Subsequently, these PUs were examined as potential drug delivery systems using Gabapentin as a model drug, which was loaded in the polymer matrix using the solvent evaporation method. The drug release studies were carried out in 0.06 N HCl as a release medium according to the method outlined in the United States Pharmacopeia. The maximum drug release was observed for sample PU-P1, which was found to be 53.0 % after 6 h. Moreover, a comparison of different PU samples revealed a trend wherein the values of drug release were decreased with an increase in the PEG content.

Quantifying Bound Proteins on Pegylated Gold Nanoparticles Using Infrared Spectroscopy.

Protein-nanoparticle (NP) complexes are nanomaterials that have numerous potential uses ranging from biosensing to biomedical applications such as drug delivery and nanomedicine. Despite their extensive use quantifying the number of bound proteins per NP remains a challenging characterization step that is crucial for further developments of the conjugate, particularly for metal NPs that often interfere with standard protein quantification techniques. In this work, we present a method for quantifying the number of proteins bound to pegylated thiol-capped gold nanoparticles (AuNPs) using an infrared (IR) spectrometer, a readily available instrument. This method takes advantage of the strong IR bands present in proteins and the capping ligands to quantify protein-NP ratios and circumvents the need to degrade the NPs prior to analysis. We show that this method is generalizable where calibration curves made using inexpensive and commercially available proteins such as bovine serum albumin (BSA) can be used to quantify protein-NP ratios for proteins of different sizes and structures.

Selective Anticervical Cancer Injectable and Self-Healable Hydrogel Platforms Constructed of Drug-Loaded Cross-Linkable Unimolecular Micelles in a Single and Combination Therapy.

In the face of severe side effects of systemic chemotherapy used in cervical cancer, topical selective drug carriers with long-lasting effects are being sought. Hydrogels are suitable platforms, but their use is problematic in the case of delivery of hydrophobic drugs with anticancer activity. Herein, hydrogels constructed of unimolecular micelles displaying enhanced solubilization of aromatic lipophilic bioactive compounds are presented. Star-shaped poly(benzyl glycidyl ether)-block-poly(glycidyl glycerol ether) with an aryl-enriched core show high encapsulation capacity of poor water-soluble nifuratel and clotrimazole. Nifuratel attained selectivity against cervical cancer cells, whereas clotrimazole preserved its original selectivity. The combination of unimolecular micelles loaded with both drugs provided synergism; however, they were still selective against cervical cancer cells. The cross-linking of drug-loaded unimolecular micelles via dynamic boronic esters provided injectable and self-healable hydrogel drug carriers also displaying synergistic anticancer activity, suitable for intravaginal administration and assuring the effective coverage of the afflicted tissue area and efficient tissue permeability with hydrophobic bioactive compounds. Here, we show that the combination of star-shaped polyether amphiphiles and boronic ester cross-linking chemistry provides a new strategy for obtaining hydrogel platforms suitable for efficient hydrophobic drug delivery.

PEGylated mesoporous silica core-shell redox-responsive nanoparticles for delivering paclitaxel to breast cancer cells.

Controlling the drug release and restricting its presence in healthy organs is extremely valuable. In this study, mesoporous silica nanoparticles (MSN) as the core, loaded with paclitaxel (PTX), were coated with a non-porous silica shell functionalized with disulfide bonds. The nanoparticles were further coated with polyethylene glycol (PEG) via disulfide linkages. We analyzed the physicochemical properties of nanoparticles, including hydrodynamic size via Dynamic Light Scattering (DLS), zeta potential, X-ray Diffraction (XRD) patterns, Fourier-Transform Infrared (FTIR) spectra, and imaging through Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). The drug release profile in two distinct glutathione (GSH) concentrations of 2 µM and 10 µM was measured. The cellular uptake of nanoparticles by MCF-7 cell line was determined using Confocal Laser Scanning Microscopy (CLSM) images and flow cytometry. Furthermore, the cell viability and the capability of nanoparticles to induce apoptosis in MCF-7 cell line were studied using the MTT assay and flow cytometry, respectively. Our investigations revealed that the release of PTX from the drug delivery system was redox-responsive. Also, results indicated an elevated level of cellular uptake and efficient induction of apoptosis, underscoring the promising potential of this redox-responsive drug delivery system for breast cancer therapy.

Auranofin-Loaded Chitosan Nanoparticles Demonstrate Potency against Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) remains a clinical challenge due to molecular, metabolic, and genetic heterogeneity as well as the lack of validated drug targets. Thus, therapies or delivery paradigms are needed. Gold-derived compounds including the FDA-approved drug, auranofin have shown promise as effective anticancer agents against several tumors. To improve the solubility and bioavailability of auranofin, we hypothesized that the nanodelivery of auranofin using biodegradable chitosan modified polyethylene glycol (PEG) nanoparticles (NPs) will enhance anticancer activity against TNBC by comparing the best nanoformulation with the free drug. The selection of the nanoformulation was based on synthesis of various chitosan PEG copolymers via formaldehyde-mediated engraftment of PEG onto chitosan to form [chitosan-g-PEG] copolymer. Furthermore, altered physiochemical properties of the copolymer was based on the formaldehyde ratio towards nanoparticles (CP 1-4 NPs). Following the recruitment of PEG onto the chitosan polymer surface, we explored how this process influenced the stiffness of the nanoparticle using atomic force microscopy (AFM), a factor crucial for in vitro and in vivo studies. Our objective was to ensure the full functionality and inherent properties of chitosan as the parent polymer was maintained without allowing PEG to overshadow chitosan's unique cationic properties while improving solubility in neutral pH. Hence, CP 2 NP was chosen. To demonstrate the efficacy of CP 2 NP as a good delivery carrier for auranofin, we administered a dose of 3 mg/kg of auranofin, in contrast to free auranofin, which was given at 5 mg/kg. In vivo studies revealed the potency of encapsulated auranofin against TNBC cells with a severe necrotic effect following treatment superior to that of free auranofin. In conclusion, chitosan-g-PEG nanoparticles have the potential to be an excellent delivery system for auranofin, increasing its effectiveness and potentially reducing its clinical limitations.

Enhanced theranostic efficacy of epirubicin-loaded SPION@MSN through co-delivery of an anti-miR-21-expressing plasmid and ZIF-8 hybridization to target colon adenocarcinoma.

Using targeted drug delivery systems has emerged as a promising approach to increase the efficacy of chemotherapy, particularly in combination with gene therapy. The overexpression of miR-21 plays a crucial role in colorectal cancer (CRC) progression, and targeted inhibition of miR-21 offers significant potential for enhancing CRC chemotherapy outcomes. In this study, a theranostic system based on mesoporous silica and superparamagnetic iron oxide nanoparticles (SPION@MSNs) was synthesized as a core-shell structure. After loading epirubicin (EPI) in the open pores of MSN, the plasmid expressing anti-miR-21 (pDNA) covered the outer surface with the help of a ZIF-8 (zeolitic imidazolate framework-8) film. Afterward, polyethylene glycol (PEG) and AS1411 aptamer were conjugated to the surface to improve the protective, biocompatibility, and targeting abilities of the nanocarrier. Moreover, the physicochemical characteristics as well as the loading capacity and release profile of EPI and pDNA were fully evaluated. The uptake of the nanoparticles by CRC and normal cell lines in addition to the anticancer effects related to targeted combinational therapy were investigated in vitro. Finally, in vivo tests were performed on BALB/c mice bearing colorectal tumors to evaluate the effectiveness of the targeted nanoparticles, their possible side effects, and also their application in fluorescence and magnetic imaging in vivo. The successful synthesis of SPION@MSN-EPI/pDNA-ZIF-8-PEG-Apt nanoparticles (∼68 nm) and good loading efficiency and controlled release of EPI and pDNA were confirmed. Moreover, hemolysis and gel retardation assays demonstrated the biocompatibility and plasmid protection. Cellular uptake and expression of copGFP illustrated selective entry and transient transfection of targeted nanoparticles, consistent with the cytotoxicity results that indicated the synergistic effects of chemo-gene therapy. The results of animal studies proved the high antitumor efficiency of targeted nanoparticles with minimal tissue damage, which was in line with fluorescence and magnetic imaging results. The novel synthesized nanoparticles containing SPION@MSN-ZIF-8 were suitable for CRC theranostics, and the combined approach of chemo-gene therapy suppressed the tumor more effectively.

Cu-MSNs and ZnO nanoparticles incorporated poly(ethylene glycol) diacrylate/sodium alginate double network hydrogel for simultaneous enhancement of osteogenic differentiation.

In this study, a double network (DN) hydrogel was synthesized using poly(ethylene glycol) diacrylate (PEGDA) and sodium alginate (SA), incorporating copper-doped mesoporous silica nanospheres (Cu-MSNs) and zinc oxide nanoparticles (ZnO NPs). The blending of PEGDA and SA (PS) facilitates the double network and improves the less porous microstructure of pure PEGDA hydrogel. Furthermore, the incorporation of ZnO NPs and Cu-MSNs into the hydrogel network (PS@ZnO/Cu-MSNs) improved the mechanical properties of the hydrogel (Compressive strength = ⁓153 kPa and Young's modulus = ⁓ 1.66 kPa) when compared to PS hydrogel alone (Compressive strength = ⁓ 103 kPa and Young's modulus = ⁓ 0.95 kPa). In addition, the PS@ZnO/Cu-MSNs composite hydrogel showed antibacterial activities against Staphylococcus aureus and Escherichia coli. Importantly, the PS@ZnO/Cu-MSNs hydrogel demonstrated excellent biocompatibility, enhanced MC3T3-E1 cell adhesion, proliferation, and significant early-stage osteoblastic differentiation, as evidenced by increased alkaline phosphatase (ALP), and improved calcium mineralization, as evidenced by increased alizarin red staining (ARS) activities. These findings point to the possible use of the PS@ZnO/Cu-MSNs composite hydrogel in bone tissue regeneration.

Glycerol- and diglycerol-based polyesters: Evaluation of backbone alterations upon nano-formulation performance.

Despite the success of polyethylene glycol-based (PEGylated) polyesters in the drug delivery and biomedical fields, concerns have arisen regarding PEG's immunogenicity and limited biodegradability. In addition, inherent limitations, including limited chemical handles as well as highly hydrophobic nature, can restrict their effectiveness in physiological conditions of the polyester counterpart. To address these matters, an increasing amount of research has been focused towards identifying alternatives to PEG. One promising strategy involves the use of bio-derived polyols, such as glycerol. In particular, glycerol is a hydrophilic, non-toxic, untapped waste resource and as other polyols, can be incorporated into polyesters via enzymatic catalysis routes. In the present study, a systematic screening is conducted focusing on the incorporation of 1,6-hexanediol (Hex) (hydrophobic diol) into both poly(glycerol adipate) (PGA) and poly(diglycerol adipate) (PDGA) at different (di)glycerol:hex ratios (30:70; 50:50 and 70:30 mol/mol) and its effect on purification upon NPs formation. By varying the amphiphilicity of the backbone, we demonstrated that minor adjustments influence the NPs formation, NPs stability, drug encapsulation, and degradation of these polymers, despite the high chemical similarity. Moreover, the best performing materials have shown good biocompatibility in both in vitro and in vivo (whole organism) tests. As preliminary result, the sample containing diglycerol and Hex in a 70:30 ratio, named as PDGA-Hex 30%, has shown to be the most promising candidate in this small library analysed. It demonstrated comparable stability to the glycerol-based samples in various media but exhibited superior encapsulation efficiency of a model hydrophobic dye. This in-depth investigation provides new insights into the design and modification of biodegradable (di)glycerol-based polyesters, potentially paving the way for more effective and sustainable PEG-free drug delivery nano-systems in the pharmaceutical and biomedical fields.

Validation of a human saliva model for the determination of leachable monomers and other chemicals from dental materials.

This study aimed to prove the validity of a mixture of chemicals, including salts, small organic molecules, mucin, and α-amylase, as saliva surrogate ("artificial saliva") for assessing leakage of methacrylate monomers and other constituents from dental materials. To achieve this, we developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA), diurethane dimethacrylate (UDMA), bisphenol A glycerolate dimethacrylate (BisGMA), diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO), bisphenol A (BPA), and five homologues of ethoxylated bisphenol A dimethacrylate (BisEMA EO2-6) in unstimulated and artificial saliva, and compared their concentrations in the two saliva media following either spiking with a mixture of the compounds or incubation of test specimens of printed biomaterials. Test specimens were immersed in unstimulated/artificial saliva, incubated at 37 °C for 24 h, and saliva aliquots were extracted with methanol and subsequently analyzed by LC-MS/MS. The method was validated with regard to matrix effects, linearity, selectivity, lower limits of quantification (LLOQ), precision, bias and combined measurement uncertainty (u'). The performance characteristics of the method were comparable for unstimulated and artificial saliva samples. The combined u' for individual chemicals at a concentration of 10 × LLOQ were within the range of 5.3-14 % for unstimulated saliva and 6.9-16 % for artificial saliva, except for the BisEMA homologues. Combined u' for the latter were 27-74 % in unstimulated saliva, and 27-79 % in artificial saliva. There was no detectable release of BPA from the test specimens, and the TPO concentrations were mainly below the LLOQ. TEGDMA and UDMA were detected in the highest quantities, and at comparable concentrations in the unstimulated and artificial saliva. For all BisEMA homologues, the release was higher in unstimulated saliva than in artificial saliva. The study showed that the artificial saliva model can be a suitable replacement for native saliva, but might underestimate leakage of more lipophilic methacrylates.

Bacteria-Targeting Nanoparticles with ROS-Responsive Antibiotic Release to Eradicate Biofilms and Drug-Resistant Bacteria in Endophthalmitis.

Background: Bacterial endophthalmitis is an acute progressive visual threatening disease and one of the most important causes of blindness worldwide. Current treatments are unsatisfactory due to the emergence of drug-resistant bacteria and the formation of biofilm. Purpose: The aim of our research was to construct a novel nano-delivery system with better antimicrobial and antibiofilm effects. Methods: This study developed a novel antibiotic nanoparticle delivery system (MXF@UiO-UBI-PEGTK), which is composed of (i) moxifloxacin (MXF)-loaded UiO-66 nanoparticle as the core, (ii) bacteria-targeting peptide ubiquicidin (UBI29-41) immobilized on UiO-66, and (iii) ROS-responsive poly (ethylene glycol)-thioketal (PEG-TK) as the surface shell. Then the important properties of the newly developed delivery system, including biocompatibility, toxicity, release percentage, thermal stability, ability of targeting bacteria, and synergistic antibacterial effects on bacterial biofilms and endophthalmitis, were evaluated. Results: In vitro, MXF@UiO-UBI-PEGTK exhibited significant antibiotic effects including the excellent antibiofilm property against Staphylococcus aureus, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus at high levels of ROS. Moreover, MXF@UiO-UBI-PEGTK demonstrated outstanding efficacy in treating bacterial endophthalmitis in vivo. Conclusion: This novel nanoparticle delivery system with ROS-responsive and bacteria-targeted properties promotes the precise and effective release of drugs and has significant potential for clinical application of treating bacterial endophthalmitis.

Characterization of PEGylation sites in Neulasta and a biosimilar candidate with a combined fragmentation strategy in mass spectrometry analysis.

In the development of biosimilar products to Neulasta, it is essential to determine the intact molecular mass and confirm precise PEGylation sites. In this study, we applied a combination of techniques, including post-column addition of triethylamine in reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) to determine the intact molecular mass, and in-source fragmentation (ISF) and higher-energy collision dissociation-tandem mass spectrometry (HCD-MS/MS) to identify the PEGylation site. Our results show that both the pegfilgrastim biosimilar candidate and Neulasta lots are mono-PEGylated at the N-terminal end. Furthermore, we show that the combined ISF and HCD-MS/MS method can be used for identifying the PEGylation sites in the diPEGylated variant of pegfilgrastim. The diPEGylated variant has modification sites at the N-terminal end and a lysine at position 35 in the protein sequence.

Aging processes in dental thermoplastics - Thermoanalytical investigations and effects on Vickers as well as Martens hardness.

OBJECTIVE: The influence of various aging protocols, representing and accelerating influences present in the dental context, on possible changes in the microstructure and mechanical properties of thermoplastics was investigated. In order to minimize the complexity of the systems, first pure polymers and then later the equivalent dental polymeric materials were analyzed. MATERIALS AND METHODS: Pure polymers (Poly(methyl methacrylate) - PMMA, Polyoxymethylene homopolymer - POM-H, Polyether ether ketone - PEEK, Nylon 12 - PA12, Polypropylene - PP) were analyzed before as well as after applying different aging protocols relevant to the oral environment (ethanol, thermocycling, alkaline and acidic setting) by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The thermoanalytical parameters used were glass transition temperature (Tg), melting peak and crystallization peak temperature (Tpm, Tpc) and decomposition behavior. In a second step selected commercially available dental products (Telio CAD - PMMAD, Zirlux Acetal - POMD, Juvora Natural Dental Disc - PEEKD) aged by the protocol that previously showed strong effects were examined and additionally tested for changes in their Vickers and Martens hardness by Mann-Whitney-U test. RESULTS: The combinations of pure polymers and viable aging protocols analyzed within this study were identified via TGA or DSC as PA12 & thermocycling, POM-H & denture cleanser/lactic acid/ethanol, PP & lactic acid. The dental polymeric materials PMMAD and POMD due to aging in lactic acid showed slight but significantly (p < 0.01) reduced Vickers and partly Martens hardness. PEEK showed the greatest material resistance within this study.