Search Results (351)

This study reports poly(acrylic acid) (PAA)-containing ceria slurries for shallow trench isolation (STI) chemical mechanical polishing (CMP). HNU15 ceria nanoparticles were prepared by precipitation at room temperature. PAA was synthesized by aqueous free-radical polymerization, characterized by gel permeation chromatography and Fourier-transform infrared spectroscopy, and used as the polymeric dispersant in both HNU15 and commercial HC10 slurries. The primary-particle sizes determined by TEM were 12.2 ± 1.5 nm for HNU15 and 14.6 ± 1.4 nm for HC10, whereas the crystallite sizes calculated from XRD were 10.2 nm and 8.7 nm, respectively. HNU15 showed a higher BET surface area and Ce³⁺ fraction than HC10, indicating measurable differences in textural properties and surface chemical states. After 5 h of milling, the HNU15 and HC10 slurries exhibited DLS d₅₀ values of 111 nm and 122 nm and zeta potentials of −53.60 mV and −49.40 mV, respectively. Both slurries maintained generally stable colloidal properties during four weeks of storage at 25 °C and 60 °C. Under the laboratory CMP conditions, HNU15 slurry exhibited an HDP-SiO₂ removal rate of 114.4 Å min⁻¹, an HDP-SiO₂-to-Si₃N₄ selectivity of 8.0, and lower post-polishing roughness than HC10. These results support the use of the PAA-containing HNU15 slurry for STI CMP applications. Full article

A biological/synthetic hybrid graft copolymer was obtained by grafting poly(acrylic acid) (PAA, synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization) to amylopectin (AMP). The novel graft copolymer presents amphiphilic properties due to the inherent insolubility of AMP in water and was further utilized as a mediator for the synthesis of gold nanoparticles (AuNPs) following an environmentally friendly in situ procedure. The AMP-g-PAA copolymer formation by the interaction of the PAA end groups with the C(6)-OH groups on an AMP backbone was confirmed by Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) and 1D (proton (¹H NMR) and carbon (¹³C NMR) nuclear magnetic resonance, and Distortionless Enhancement by Polarization Transfer (DEPT)) and 2D (correlation (COSY) and heteronuclear single quantum coherence (HSQC)) spectroscopies. The calculated degree of substitution of 1.17 suggests that the grafting was done at one OH from the three in an anhydroglycosidic unit (AGU) (preferably at that in C6 position), with a mean grafting efficiency of 76%. Additional information obtained using thermogravimetric analysis shows that the thermal decomposition of AMP-g-PAA occurs in two steps, with a residual mass of ~16 wt% at 700 °C, higher than AMP or PAA, indicating increased thermal stability of the copolymer. Dynamic and electrophoretic light scattering (DLS and ELS) measurements were used to determine the hydrodynamic size and ionic charge of the AMP-g-PAA self-assemblies in aqueous solution as well as their stability. The AMP-g-PAA was subsequently tested as a reducing agent in the environmentally friendly synthesis of AuNPs in aqueous solution, at different incubation temperatures, reaction duration, and inorganic/polymer weight ratios. The development of the surface plasmon resonance band of AuNPs, observed in UV–vis spectra, was consistently monitored over the reaction time. DLS analysis indicated time-dependent changes in the AuNPs’ particle size distributions, while scanning transmission electron microscopy confirmed that the AuNPs formed at the inorganic/polymer weight ratio of 0.36 and at 60 °C were predominantly well-dispersed, spherical-shaped nanoparticles. The AuNPs synthesized in situ within the copolymer matrix did not introduce additional cytotoxicity compared to the parent copolymer alone, with the composites representing a promising safety baseline for further investigation in biomedical applications. Full article

Poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) copolymer micelles have emerged as promising drug delivery systems for enhancing the solubility and bioavailability of poorly water-soluble benzimidazole drugs. In this study, we prepared and characterized PEG-b-PCL micelles to encapsulate poorly water-soluble anthelmintics such as albendazole (ABZ) and fenbendazole (FBZ), with a focus on comparing their encapsulation behaviour, release profiles, and biological activity in cancer therapy. Drug-loaded micelles were analysed using dynamic light scattering (DLS), which revealed uniform nanosized micelles with a narrow polydispersity index (PDI). The morphology and size of both empty and drug-loaded micelles were examined using transmission electron microscopy (TEM), confirming that the micelles were spherical and consistent in size. Both drugs were efficiently encapsulated within the micellar core, demonstrating a high loading capacity. The release profiles of PEG-b-PCL micelles containing albendazole (ABZ) and fenbendazole (FBZ) at pH 7.4 were also evaluated. FBZ exhibited slower release kinetics compared to ABZ, likely due to its higher lipophilicity and stronger interactions with the hydrophobic PCL core, resulting in enhanced retention within the micelles. In contrast, ABZ had faster release kinetics. Finally, the in vitro MTT assays performed on the highly invasive triple-negative breast cancer (TNBC) cell line revealed the potential of these micelles as effective drug delivery systems. Full article

Ascorbic acid plays an important role in the human body due to its antioxidant and anti-inflammatory properties, as well as its involvement in collagen synthesis, enzymatic regulation, and the biosynthesis of corticosteroids and selected neurotransmitters. Owing to these diverse functions, it is used both in the prevention and supportive treatment of several disorders and as a mild, non-toxic reducing agent in the synthesis of gold nanoparticles (AuNPs). In the present study, a method for synthesizing gold nanoparticles was developed using second-generation poly(amidoamine) dendrimers (PAMAM G2) with an ethylenediamine core as stabilizing agents and ascorbic acid as the reducing agent. The synthesis was performed using two techniques: sonication and microwave irradiation. A comparative analysis was conducted for colloidal systems obtained at various molar ratios of PAMAM G2 dendrimers to chloroauric acid (ranging from 1:1 to 1:5). The presence of gold nanoparticles was confirmed using ultraviolet–visible spectroscopy (UV–Vis). Nanoparticle diameters and zeta potentials were determined by dynamic light scattering (DLS). The sizes of the metallic cores were estimated using scanning transmission electron microscopy (STEM). Furthermore, the morphology and topography of entire complexes deposited on silicon substrates were visualized using atomic force microscopy (AFM). For cytotoxicity studies on human breast adenocarcinoma and human osteosarcoma cell lines, the most stable colloids—those obtained at a PAMAM G2:HAuCl₄ molar ratio of 1:3—were selected. Results indicate that the synthesized nanoparticles exhibit slightly higher cytotoxicity compared with AuNPs/PAMAM G2 complexes reduced with sodium citrate, as evidenced by lower EC₅₀ values (the concentration responsible for reducing cell viability to 50%). It should be emphasized, however, that AuNPs/PAMAM G2 reduced with ascorbic acid are significantly smaller, with diameters of approximately 10 nm, whereas citrate-reduced nanoparticles exhibit diameters of around 20 nm. These results indicate that nanoparticle size, rather than the chemical nature of the reducing agent, is a dominant factor governing the cytotoxic response of AuNPs/PAMAM G2 complexes. Full article

Amphiphilic statistical copolymers are valuable synthetic macromolecules for the formation of small, well-defined nanoassemblies able to be utilized as nanocarriers for drug and/or gene delivery applications. In this work, the synthesis of amphiphilic linear statistical copolymers of the poly(benzyl methacrylate-co-dimethylaminoethyl methacrylate) [P(BzMA-co-DMAEMA)] type is described in three different comonomer compositions. Their synthesis was realized through a one-pot reversible addition-fragmentation chain transfer (RAFT) solution polymerization scheme. Further quaternization of the amine groups of DMAEMA with methyl iodide (CH₃I) resulted in cationic amphiphilic statistical copolymers. Macromolecular characterization was performed using size exclusion chromatography (SEC) and spectroscopic techniques (¹H-NMR and ATR-FTIR). The aggregation properties of the copolymers in aqueous media were studied via dynamic light scattering (DLS) and electrophoretic light scattering (ELS). Bimodal size distributions were determined in some cases. The BzMA to DMAEMA ratio determined aggregate size, with the copolymer of lower hydrophobic BzMA content producing smaller nanoparticles. Cryogenic transmission electron microscopy (cryo-TEM) showed the presence of spherical assemblies resulting from aggregation of primary micelles in the case of higher BzMA content. The copolymer aggregates experience dissociation at high salt concentration, and the pH-responsiveness of the amine precursors results in the formation of multifunctional potential nanocarriers. Full article

Background/Objectives: This paper describes the synthesis of silica nanoparticles (SiNPs) and their surface modification with amino and phosphate groups (SiNPs-NH₂-PO₃). The functionalized nanoparticles were subsequently loaded with the anticancer drug 5-fluorouracil (SiNPs-NH₂-PO₃-5-FLU) and further modified with PEG2000 (SiNPs-NH₂-PO₃-5-FLU-PEG2000). Methods: In this study, a one-step, two-phase, sol–gel method carried out at room temperature was used to synthesize the nanoparticles. The size and surface zeta potential of the created SiNPs were determined by DLS measurements. HPLC was used to determine the amount of drug loaded into silica nanoparticles and the drug release profile in two different pH environments (slightly acidic and physiological). Based on physicochemical characteristics, the SiNPs-NH₂-PO₃-5-FLU and SiNPs-NH₂-PO₃-5-FLU-PEG2000 formulations were chosen for comprehensive characterization. The cytotoxicity of the studied complexes was assessed in MCF7 breast cancer cells, while their ability to induce apoptosis in those cells was examined using specific immunofluorescence markers: active caspase-7, active poly(ADP-ribose) polymerase (PARP), and p53 protein. Results: Our findings demonstrate that SiNPs-NH₂-PO₃-5-FLU can induce a stronger apoptotic response than free 5-FLU at equivalent concentrations. We observed that drug release occurs not only under physiological conditions but is further enhanced in a mildly acidic environment (pH 5.0), characteristic of the tumor microenvironment. Conclusions: Most 5-fluorouracil formulations are administered as injectable solutions, resulting in systemic exposure and significant adverse effects. However, their encapsulation within nanoparticles could favor preferential drug release in the acidic tumor microenvironment, thus supporting targeted therapy and reducing toxicity to healthy tissues. Moreover, PEGylation of the nanoformulation allows prolonged and controlled release. Full article

Dispersion stabilization of nanoparticles for catalytic reactions is an important issue. However, dispersing agents should be carefully selected not to hinder catalytic performance. In the present study, physisorption of cyclic poly(ethylene glycol) (c-PEG) onto platinum nanoparticles (PtNPs) was investigated in comparison with unmodified PtNPs (PtNPs/No PEG), PtNPs mixed with linear PEG (PtNPs/HO-PEG-OH), and PtNPs chemisorbed with HS-PEG-OMe (PtNPs/HS-PEG-OMe). DLS showed a significant increase in the particle size for PtNPs/c-PEG and PtNPs/HS-PEG-OMe compared to PtNPs/No PEG and PtNPs/HO-PEG-OH. ζ-potential measurements revealed values around −30 mV for PtNPs/No PEG and PtNPs/HO-PEG-OH, whereas PtNPs/c-PEG and PtNPs/HS-PEG-OMe approached 0 mV, which indicated that c-PEG and HS-PEG-OMe adsorb onto PtNPs to form a shielding layer. Moreover, PtNPs/c-PEG and PtNPs/HS-PEG-OMe were stable in a phosphate-buffered saline (PBS) solution, but PtNPs/No PEG and PtNPs/HO-PEG-OH immediately aggregated. This suggests that high dispersion stability by c-PEG is comparable to ordinary surface modification using HS-PEG-OMe. Furthermore, the catalytic ability of PtNPs/c-PEG and PtNPs/HS-PEG-OMe was compared in various reactions. As a result, physisorbed PtNPs/c-PEG showed suitable catalytic activities, whereas chemisorbed PtNPs/HS-PEG-OMe was significantly hampered by the blocking of the catalytic sites with thiol in some reactions. Thus, physisorption of c-PEG endows PtNPs with dispersion stability and maintains the catalytic ability, leading to an alternative way of modifying metal nanoparticles. Full article

Background: Currently marketed hepatitis B vaccines are primarily recombinant protein vaccines. However, their antigen immunogenicity is relatively weak, requiring combination with effective adjuvants to enhance the immune response. The development of novel, highly effective adjuvants is a key strategy for optimizing vaccine performance. Polyinosinic-polycytidylic acid (PolyI:C), a synthetic double-stranded RNA analog, activates TLR3/RLR pathways to enhance T-cell priming and cellular immunity. However, its utility as a sole adjuvant is limited by rapid nuclease degradation and poor cytosolic delivery. Lipid nanoparticles (LNPs), a mature delivery platform, enable high encapsulation efficiency, efficient cellular uptake, and endosomal escape. Objectives: This study aimed to evaluate the adjuvant effect of LNP-encapsulated PolyI:C (LNP-PolyI:C) on the immunogenicity of hepatitis B surface antigen (HBsAg) in vivo. Methods: The colloidal stability of LNP-PolyI:C stored at 2–8 °C for 9 months was monitored using dynamic light scattering (DLS) on a Zetasizer Lab instrument. Serum levels of HBsAg-specific IgG, IgG1, and IgG2a antibodies in immunized Kunming mice were measured by enzyme-linked immunosorbent assay (ELISA). The secretion of HBsAg-specific cytokines by splenocytes was analyzed using flow cytometry and enzyme-linked immunospot (ELISpot) assay. Results: The results demonstrated that the LNP-encapsulated PolyI:C adjuvant significantly increased the secretion of HBsAg-specific IFN-γ, IL-2, and TNF-α by splenocytes, indicating a Th1-biased and cytotoxic T lymphocyte (CTL)-mediated cellular immune response. In addition, this formulation markedly elevated serum titers of HBsAg-specific IgG, IgG1, and IgG2a. Conclusions: These findings underscore the advantages of the LNP-PolyI:C adjuvant in enhancing both humoral and cellular immunity, demonstrating its considerable potential as a novel adjuvant. Full article

Background: Paramagnetic manganese (Mn(II)) has emerged as a promising alternative to gadolinium-based contrast agents (GBCAs) due to its favorable magnetic properties. Despite extensive research, no Mn-based agent has yet achieved clinical translation. Because free Mn(II) is toxic, macromolecular complexes incorporating stable macrocyclic DOTA chelators conjugated to polysaccharides may enhance coordination stability and improve the safety profile of Mn(II)-based contrast agents. Methods: Two chemical routes, maleimide- and ester-mediated, were evaluated for covalent coupling of DOTA-based macrocyclic ligands to the backbone of selected poly- and oligosaccharides. Subsequently, DOTA-modified carboxymethyldextran, aminodextran, and chitosan oligosaccharide were labeled with paramagnetic Mn(II) under mild conditions. ATR-FTIR confirmed the successful conjugation of DOTA chelators to the sugar backbone. The conjugates were further characterized by DLS, ICP-MS, and FPLC. In vitro relaxivity was measured at high field strength to evaluate MRI performance. In vivo contrast efficacy was first assessed using in ovo MRI in chicken embryos and subsequently evaluated by biodistribution studies in nude mice. Results: In vitro relaxivity studies demonstrated higher signal enhancement of the poly-/oligosaccharide-DOTA-Mn(II) conjugates compared with MnCl₂ and the clinical agent gadoteridol (ProHance^®). In ovo MRI showed persistent vascular enhancement up to 120 min, while in nude mice, contrast enhancement was observed in the liver, kidneys, and gallbladder 40 min post-injection. Conclusions: Mn(II)-tagged sugar-based imaging probes may offer a promising non-gadolinium alternative to GBCAs, with tunable biodistribution profiles depending on carrier molecular weight. Full article

There has been much development of composites of calcium phosphate and polymers for use as artificial bone, with other applications still ongoing, and clarification of the in vivo absorption mechanism is considered an important perspective. In order to clarify the absorption mechanism of bioabsorbable materials used for artificial bones and bone grafts, we prepared composites of calcium phosphate and polymers and conducted in vivo experiments in experimental animals using composites as implantation samples. Two typical types of calcium phosphate, β-tricalcium phosphate (β-TCP) and unsintered hydroxyapatite (uHA), were used as calcium phosphate, and copolymers of poly-dl-lactide-co-glycolide (PDLGA) and poly-l-lactide-co-glycolide (PLGA) were used as polymers. For samples composed of PDLGA and calcium phosphates, the weight ratios of calcium phosphate were set at 40% and 10% for uHA and 40% for β-TCP (uHA(40), uHA(10) and β-TCP(40), respectively). A composite sample of PLGA and uHA was also prepared with a weight ratio of 10% uHA (uHA(10)/PLGA), intending slow degradation of the polymer matrix compared to PDLGA. The samples were implanted in the metaphysis and diaphysis region of rabbits’ femur for up to 48 weeks. In this study, positron emission tomography/X-ray computed tomography (PET/CT) was used to continuously evaluate the changes in the samples and the accumulation of cells in the animals, and histological evaluation was performed, focusing on the time of characteristic changes in the PET/CT to confirm the cell types. The results are summarized as follows: (1) the absorption mechanism of the materials used in this study was suggested to be mainly phagocytosis by macrophages; (2) the disappearance rate was faster for β-TCP(40) compared with uHA(40); and (3) uHA(10), having a lower proportion of uHA, is not prone to aggregation and exhibited a similar disappearance result to β-TCP(40). These results suggest that phagocytosis by macrophages is the dominant path in resorption of the bioresorbable materials, and the resorption period varies depending on the type of polymer. It is important to optimize the type and amount of polymers and calcium phosphate in order to achieve a degradation rate of bioresorbable materials that corresponds to the extent of damage in the healing area. Full article

Background/Objectives: Current clinical evidence suggests that cannabidiol (CBD) demonstrates therapeutic potential in the management of chronic pain, particularly in conditions involving inflammation. However, its therapeutic potential is severely limited by poor oral bioavailability, extensive first-pass metabolism, and the need for frequent high-dose administration, which compromises patient adherence and tolerability. Long-acting injectable (LAI) delivery systems offer a strategy to overcome these limitations by providing sustained plasma concentrations and reducing dosing frequency. This study aimed to develop and optimise CBD-loaded poly (lactic-co-glycolic acid) (PLGA) microspheres for LAI delivery and to evaluate poly(2-ethyl-2-oxazoline) (POx) as a functional and biocompatible alternative to the conventionally used poly (ethylene glycol) (PEG). Methods: CBD-loaded microspheres were prepared using emulsion–solvent evaporation technique. The formulations were optimised based on entrapment efficiency (EE), drug loading (DL), particle size distribution, surface morphology, thermal behaviour, in vitro release kinetics, and cytocompatibility using NIH 3T3 fibroblasts. Multiple in vitro release methodologies, including dialysis bag, shaking-flask, and USP Apparatus IV, were evaluated to identify the most discriminative and practical approach for long-term release assessment. Results: The optimised POx-based microspheres demonstrated superior control over particle size, yielding significantly smaller and more uniform particles compared with PEG-based microspheres (124 ± 1.47 µm vs. 218 ± 13.5 µm, respectively). Differential scanning calorimetry (DSC) confirmed molecular dispersion of CBD within the polymer matrix. In vitro release studies demonstrated sustained drug release over 20 days. Conclusions: POx represents a promising alternative to PEG for the formulation of CBD-loaded PLGA microspheres, offering enhanced physicochemical stability and biological compatibility. This platform supports the development of safe and effective long-acting injectable CBD therapies and consideration of POx as an alternative to PEG. Full article

Protein–polyelectrolyte entities (complex, coacervates, flocs, gels, etc.) are of great interest due to their potential applications in biological and medical fields. This study focuses on investigating the interactions between a model protein, human serum albumin (HSA) and a newly synthesized hybrid thermoresponsive copolymer based on chitosan polysaccharide grafted with poly(N-isopropylacrylamide) synthetic polymer chains (Chit-g-PNIPAM), in aqueous media, by mixing the individual component aqueous solutions. Depending on the mixing molar ratio and the order of addition of the two components (protein and copolymer), either stable nanostructured suspension or macrostructures’ phase separation have been observed. Dynamic light scattering (DLS) results reveal that the Chit-g-PNIPAM/HSA_x (molar ratio 5:x, where x = 1, 2, 3, 5, 10 and 15) nanostructures’ and HSA/Chit-g-PNIPAM_x (molar ratio 100:x, where x = 1, 2, 3, 10, 20, 30, 40 and 50) structures’ formation depend on the molar ratio of the two components as well as on the order of addition, with first component amount being kept constant in aqueous solution and second component solution added drop-by-drop in the solution of the first component. Additional information regarding the thermoresponsiveness and stability vs time of the formed (nano)structures were acquired using turbidimetry and DLS measurements. Full article

The synthesis of enantiomerically pure chiral β-nitroalcohols is a crucial objective in asymmetric catalysis. In order to efficiently obtain such chiral products, we developed a series of thermoresponsive, oxazoline–copper catalysts (Cu^II-PN_xFe_yO_z) via sequential reversible addition–fragmentation chain transfer (RAFT) polymerization. These catalysts can self-assemble in water into single-chain nanoparticles (SCNPs) with biomimetic behavior, in which intramolecular hydrophobic and metal-coordination interactions generate a confined hydrophobic cavity. Comprehensive characterization by FT-IR, TEM, DLS, CD, CA, and ICP analysis confirmed the nanostructure and composition. When applied to the aqueous-phase asymmetric Henry reaction between nitromethane and 4-nitrobenzaldehyde, the optimal catalyst (2.0 mol%) achieved a quantitative yield (96%) with excellent enantioselectivity (up to 99%) within 12 h. Furthermore, the thermosensitive poly(N-isopropylacrylamide, NIPAAm) block enabled facile catalyst recovery through temperature-induced precipitation above its lower critical solution temperature (LCST). This work presents an efficient and recyclable biomimetic catalytic system, offering a novel strategy for designing sustainable chiral catalysts for green organic synthesis. Full article

Introduction: In this study, we aimed to optimize the microfluidizer-based preparation of poly(lactic-co-glycolic acid) nano-micelles (PLGANM), increasingly used for parenteral delivery of poorly water-soluble drugs but typically exhibiting poor physical stability when produced by conventional methods. Method: By systematically tuning microfluidization (MFZ) parameters, we demonstrate an efficient strategy to enhance PLGANM stability and ensure robust, scalable manufacturing, relevant for long-term storage and clinical translation applications. The influence of several key factors designed by Central Composite Design (CCD), including the amount of PLGA and Tween 80, homogenization pressure, and number of passes of MFZ on the size, polydispersity (measured by DLS), and hence stability of the PLGANM, was analyzed for 60 days. 60 PLGANMs produced by the MFZ method (PMFZ) were compared with the PLGANM consisting of equivalent amounts of PLGA and T80 produced using the traditional oil-in-water method (POW). Desired limits were set to minimize standard deviations for Z-average, Zeta Potential, and PDI. Results: Coded variables for optimized PMFZ (OPMFZ) were found to be 82.96 mg PLGA, 6.78 mL 5% T80, 11,000 psi pressure, and 1 pass. Conclusions: This study demonstrates that microfluidization, when guided by a QbD framework, offers precise control over particle attributes and enables reproducible production of stable PLGANM. Full article

Potassium (K⁺) channel blockers are promising anticancer agents but suffer from off-target toxicities. We designed cross-linked poly-2-Hydroxyethyl methacrylate (HEMA)–pectin nanogels (HPN) to deliver two model blockers—dofetilide (Dof) and azimilide (Azi)—and evaluated their physicochemical properties, release behavior, and in vitro anticancer activity. HPN was synthesized by surfactant-assisted aqueous nanogel polymerization and comprehensively characterized (FTIR, DLS, TEM/SEM, XRD, BET). The particles were monodispersed with a mean diameter ~230 nm, compatible with tumor accumulation via the Enhanced Permeability and Retention (EPR) effect, and exhibited a microporous matrix suitable for controlled release. Drug loading was higher for Dof than for Azi, with DL% values of 82.30 ± 3.1% and 17.84 ± 2.9%, respectively. Release kinetics diverged: Azi-HPN followed primarily first-order diffusion with a rapid burst, whereas Dof-HPN showed mixed zero/first-order behavior. Cytotoxicity was assessed in A549 lung cancer and BEAS-2B bronchial epithelial cells. Both free and nano-formulated blockers were selectively toxic to A549 with minimal effects on BEAS-2B. Notably, a hormesis-like pattern (low-dose stimulation/high-dose inhibition in MTT) was evident for free Dof and Azi; encapsulation attenuated this effect for Dof but not for Azi. Co-administration with paclitaxel (Ptx) potentiated Dof-HPN cytotoxicity in A549 but did not enhance Azi-HPN, suggesting mechanism-dependent drug-drug interactions. Overall, HPN provides a biocompatible platform that improves K⁺ blocker delivery. Full article