Search Results (581)

This study focused on the poly(DL-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(DL-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer, which was recently reported as a novel material for polymeric nanoparticles to replace poly(DL-lactide-co-glycolide) (PLGA) as a drug carrier for prednisolone (PSL), and aimed to evaluate the efficacy of PSL-loaded PLGA-PEG-PLGA nanoparticles (NPs) against allergic contact dermatitis (ACD). PSL-loaded PLGA-PEG-PLGA NPs were prepared using the nanoprecipitation method, and their particle size distribution and mean particle size were measured using dynamic light scattering. 1-Fluoro-2,4-dinitrobenzene (DNFB) was used to create a mouse model of contact hypersensitivity (CHS). PSL-loaded PLGA-PEG-PLGA NPs were administered before sensitization with DNFB, and the therapeutic effect was evaluated by quantifying intracutaneous TNF-α and IL-4 levels suing ELISA. When PSL-loaded PLGA-PEG-PLGA NPs were administered before sensitization, TNF-α expression and IL-4 statements were significantly lower in the PSL-loaded PLGA-PEG-PLGA NP group than in the non-treated group. No significant difference was observed between the PSL-loaded PLGA-PEG-PLGA NP and PSL-loaded ointment groups, even though the steroid dose was 40 times lower than in the PSL-containing ointment. These results suggest that PSL-loaded PLGA-PEG-PLGA NPs may have a better effect in the treatment of ACD than PSL-loaded PLGA NPs. Full article

Background/Objectives. Efficient nucleic acid delivery into target cells remains a critical challenge in gene therapy. Due to its advantages in biocompatibility and safety, recent research has increasingly focused on non-viral gene delivery. Methods. A series of copolymers—synthesized by integrating thermally sensitive poly(N-isopropylacrylamide) (PNIPAm), hydrophilic poly(ethylene glycol) (PEG) grafts, and a polycationic poly(L-lysine) (PLL) block of varying lengths ((PNIPAm)₇₇-graft-(PEG)₉-block-(PLL)_z, z = 10–65)—were investigated. Plasmid DNA complexation with the copolymers was achieved through temperature-modulated methods. The resulting polyplexes were characterized by evaluating complex strength, particle size, zeta potential, plasmid DNA loading capacity, resistance to anionic stress, stability in serum, and lysosomal membrane destabilization assay. The copolymers’ potential for plasmid DNA delivery was assessed through cytotoxicity and transfection studies in cancer cell lines. Results. Across all complexation methods, the copolymers effectively condensed plasmid DNA into stable polyplexes. Particle sizes (60–90 nm) ranged with no apparent correlation to copolymer type, complexation method, or N/P ratio, whereas zeta potentials (+10–+20 mV) and resistance to polyanionic stress were dependent on the PLL length and N/P ratio. Cytotoxicity analysis revealed a direct correlation between PLL chain length and cell viability, with all copolymers demonstrating minimal cytotoxicity at concentrations required for efficient transfection. PNL-20 ((PNIPAm)₇₇-graft-(PEG)₉-block-(PLL)₂₀) exhibited the highest transfection efficiency among the tested formulations while maintaining low cytotoxicity. Conclusions. The study highlights the promising potential of (PNIPAm)₇₇-graft-(PEG)₉-block-(PLL)_z copolymers for effective plasmid DNA delivery to cancer cells. It reveals the importance of attaining the right balance between polyplex tightness and plasmid release to achieve improved biocompatibility and transfection efficiency. Full article

Background/Objectives: The management of ocular tumours is faced with the challenge of developing a suitable treatment strategy with consideration of the anatomical and physiological protective barriers of the eye. Interferon alpha has been employed to treat patients with ocular tumours for decades; however, its short half-life and poor tolerability necessitate frequent administration. This study focuses on the design of an injectable pH-responsive and protective nanoparticle system dispersed into a thermo-responsive hydrogel for site-specific sustained delivery of interferon alpha (IFN-α2b) in the treatment of ocular surface tumours. Methods: The synthesis of a poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) triblock copolymer (PECE) was undertaken. The IFN-α2b was encapsulated in poly(β-amino ester) (PBAE) nanoparticles (NP) with pH-responsive characteristics to proposedly release the IFNα-2b in response to the acidic nature of the tumour microenvironment. This was followed by characterisation via Fourier transform infrared spectroscopy (FT-IR), ¹H-nuclear magnetic resonance (¹H-NMR) analysis, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) analysis, thermogravimetric analysis (TGA), and thermal-transition analysis of the PECE hydrogels. Results: Release studies demonstrated that the PBAE nanoparticulate PEG-PCL-PEG hydrogel was both pH-responsive, while providing controlled release of IFN-α2b, and thermo-responsive. Release analysis highlighted that IFN-α2b-loaded NP dispersed into the hydrogel (IFNH) further prolonged the release of IFN-α2b with a pH-responsive yet controlled release rate in an acidic environment simulating a tumour microenvironment. The developed system proved to be biocompatible with human retinal pigment epithelial cells and the released IFN-α demonstrated bioactivity in the presence of an A172 glioblastoma cell line. Conclusions: In conclusion, the PECE hydrogel has promising potential for application as an ocular drug delivery system for the treatment of ocular tumours and could potentially overcome and prevent the drawbacks associated with the commercially available IFN-α2b injection. Full article

The effects of a series of sodium salts (Na₃PO₄, Na₂CO₃, Na₂SO₄, Na₂SO₃, Na₂MO₄, Na₂CrO₄, and Na₂WO₄) on the phase separation of poly(ethylene glycol) (PEG) solutions in water at PEG concentrations of 0.5 to 30 wt.% were studied. The salts’ effects on phase separation are found to correlate with the change in the entropy related to the structural changes in water during anion hydration. The same salts’ effects on phase separation in aqueous solutions of branched PEG and polyvinylpyrrolidone at a polymer concentration of 10 wt.% were also examined. The results obtained support the assumption that phase separation in aqueous polymer–salt systems is an entropy-driven process. Full article

Herein we describe the development of the first model amphiphilic polymer conetwork (APCN) comprising a short hydrophobic hexa(L-alanine) segment being the outer block of an amphiphilic four-armed star block copolymer with inner poly(ethylene glycol) (PEG) blocks bearing benzaldehyde terminal groups and end-linked with another four-armed star PEG homopolymer (tetraPEG star) bearing aryl-substituted acylhydrazide terminal groups. The present successful synthesis that yielded the peptide-containing model APCN was preceded by several unsuccessful efforts that followed different synthetic strategies. In addition to the synthetic work, we also present the structural characterization of the peptide-bearing APCN in D₂O using small-angle neutron scattering (SANS). Full article

This study explores the influence of various additives on the morphological, chemical, and thermal properties of poly(vinylidene fluoride) (PVDF) membranes prepared via the non-solvent induced phase separation (NIPS) technique. The use of a green solvent such as triethyl phosphate (TEP) was shown to be successful. A particular focus was dedicated to pore formers based on choline chloride–based deep eutectic solvents (DES) in combination with ethylene glycol and glycerol, i.e., ChCl/EG and ChCl/GLY, and its benchmark with traditional counterparts such as poly(ethylene glycol) (PEG) and glycerol (GLY). Comprehensive characterization was conducted using FESEM, FTIR, XRD, and DSC techniques to evaluate changes in membrane morphology, porosity, and crystallinity. PEG acted as a pore-forming agent, transitioning the internal structure from spherulitic to sponge-like with consistent pore sizes, while GLY produced a nodular morphology at higher concentrations due to increased dope solution viscosity. DES induced significant shifts in crystalline phase composition, decreasing α-phase fractions and promoting β-phase formation at higher concentrations. While the overall porosity remained unaffected by the addition of GLY or PEG, it was dependent on the DES concentration in the dope at lower values than those obtained by GLY and PEG. Membrane pore size with ChCl/GLY was lower than with ChCl/EG and GLY. All membranes showed performance at the hydrophobic regime. The findings demonstrate that ChCl/EG and ChCl/GLY can tailor the structural and thermal properties of TEP-driven PVDF membranes, providing a green and versatile approach to customize the membrane properties for specific applications. Full article

Polypyrrole (PPy) is cationic in its conducting form, requiring a charge-balancing counterion, or dopant. The release of bioactive dopants, driven by the reduction of PPy films, offers a route to controlled drug delivery. Thiol-terminated long chain poly (ethylene glycol) (PEG) reacts with a dodecylbenzene sulfonate (DBSA)-doped PPy, forming a dense overlayer and partially liberating DBSA via the chemical reduction of the film. The resulting PEG brush acts as a barrier to dopant diffusion from the film, but proteins have been shown to disrupt this layer, releasing the DBSA. The mechanism by which this disruption occurs has not been thoroughly investigated. In this study, dopant release from PEG-PPy composites was examined via systematic exposure to a variety of chemical stimuli, including macromolecules such as poly (ethylene imine), polyethylene glycol, and poloxamers, as well as small-molecular-weight alcohols, carboxylic acids, and amines. Dopant release was quantified by quartz crystal microbalance. Poly (ethylene imine) efficiently released DBSA, while anionic and uncharged macromolecules did not. All classes of small molecules triggered dopant release, with longer homologues magnifying the response. The mechanisms of dopant removal are dependent on the functional groups of the stimulating agent and include ion exchange and nucleophilic reduction of the polycationic backbone. Tosylate, salicylate, and penicillin dopants showed release behaviors similar to DBSA, demonstrating the generality of the PEG barrier. Full article

The development of effective drug delivery systems (DDSs) is important for cancer and infectious disease treatment to overcome low bioavailability, rapid clearance and the toxicity of the therapeutic towards non-targeted healthy tissues. This review discusses how PEGylation, the attachment of poly(ethylene glycol) (PEG) molecules to nanoparticles (NPs), enhances drug pharmacokinetics by creating a “stealth effect”. We provide the synthesis methods for several PEG derivatives, their conjugation with NPs, proteins and characterization using modern analytical tools. This paper focuses particularly on covalent conjugation and self-assembly strategies for successful PEGylation and discusses the influence of PEG chain length, density and conformation on drug delivery efficiency. Despite the PEGylation benefits, there are several challenges associated with it, including immunogenicity and reduced therapeutic efficacy due to accelerated blood clearance. Therefore, the balance between PEGylation benefits and its immunogenic risks remains a critical area of investigation. Full article

To enhance the biocompatibility and drug delivery efficiency of graphene oxide (GO), poly(ethylene glycol) (PEG), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), or its triblock copolymer PEG-PHBV-PEG (PPP) were used to chemically modify GO. However, it is still unknown whether non-toxic polymer-modified GO mediates muscle toxicity or triggers intramuscular inflammation. This study aims to investigate the biological reactivity and inflammation/immune response induced by PEG, PHBV, or PPP modified GO when injected into the tibialis anterior (TA) muscle of mice prior to drug loading. The results showed that after muscle exposure, the coating of biocompatible polymers on GO is more likely to provoke muscle necrosis. Muscle regeneration was found to occur earlier and more effectively in muscle treated with hydrophilic PEG-GO and PPP-GO compared to muscle treated with hydrophobic PHBV-GO. When observing the transient muscle macrophage invasion of three modified GOs, PHBV-GO caused severe muscle necrosis in the early stage, induced a delayed peak of macrophage aggregation, and caused severe inflammatory progression. All three kinds of modified GO induced T cell aggregation to varying degrees, but PEG-GO induced early mass muscle recruitment of CD4⁺ T cells and was more sensitive to cytotoxic T cells. Based on the higher biocompatibility of PPP-GO in muscles, PPP-GO was implanted into the muscles of old or adult mice. Compared to adult mice, aged mice are more vulnerable to the stress from PPP-GO, as demonstrated by a delayed inflammatory response and muscle regeneration. Full article

Hydrogels are extensively utilized in biomedical fields because of their remarkable properties, including biocompatibility, high water content, flexibility, and elasticity. However, despite substantial progress in hydrogel research, creating a hydrogel adhesive that integrates high stretchability, fatigue resistance, and reversible adhesion continues to pose significant challenges. In this study, we aimed to address these challenges by preparing hydrogels using a combination of acrylic acid, acrylamide, carboxymethylcellulose methacrylate, thiol-functionalized polyhedral oligomeric silsesquioxane, and poly(ethylene glycol) dimethacrylate (PEGDM). By systematically varying the molecular weight of PEG, we were able to precisely adjust the mechanical and adhesive properties of the hydrogels. Our research revealed that a PEG molecular weight of 2000 (resulting in P1 hydrogel) provided a notable adhesive strength of 717.2 kPa on glass surfaces. This performance is particularly impressive given the challenges associated with achieving high adhesive strength while maintaining other desirable hydrogel properties. Beyond its strong adhesive capabilities, the P1 hydrogel also demonstrated exceptional stretchability, support, and fatigue resistance. These characteristics are crucial for applications where the adhesive needs to endure repeated stress and deformation without losing effectiveness. The successful development of P1 hydrogel underscores its potential as a multifunctional adhesive material with a broad range of applications. The ability to tailor the properties of hydrogels through molecular weight adjustments offers a promising approach to creating advanced adhesive solutions that meet the demanding requirements of modern biomedical and industrial applications. Full article

Background: Temozolomide (TMZ) is the first-line therapy for glioblastoma (GBM), but its clinical efficacy is limited by its short half-life, poor brain targeting, adverse side effects, and the development of drug resistance. Ligustilide (LIG) has been shown to enhance blood-brain barrier permeability and reduce P-glycoprotein activity, thereby potentiating the synergistic effect of TMZ against GBM. Methods: The dual-drug-loaded nanoparticles encapsulating both TMZ and LIG (TMZ/LIG-NPs) were prepared using Poly (d,l-lactic-co-glycolide)-monomethoxy poly (ethylene glycol) (PLGA-mPEG). The physicochemical properties of the NPs, including particle size and zeta potential, were characterized. Cellular uptake of NPs was evaluated using flow cytometry and fluorescence staining. The pharmacokinetic profile and cytotoxicity of TMZ/LIG-NPs were compared to those of free TMZ and a mixture of TMZ and LIG in rat and glioma cells, respectively. Results: The mean particle size of TMZ/LIG-NPs was 117.6 ± 0.7 nm, with a zeta potential of −26.5 ± 0.4 mV. Cellular uptake of NPs was significantly higher than that of free drug in U251 cells. Encapsulation of TMZ in NPs significantly increased its half-life by 1.62-fold compared to free TMZ and significantly improved its pharmacokinetic profile. Moreover, the storage stability of the TMZ/LIG-NPs solution was extended to one month. The toxicity of TMZ/LIG-NPs to glioma cells C6 and U251 was markedly enhanced compared to the mixture of TMZ and LIG. Conclusions: The development of TMZ/LIG-NPs using PLGA-mPEG effectively enhanced the stability and efficacy of both TMZ and LIG. This dual drug-loaded nanoparticle system represents a promising strategy for glioblastoma therapy. Full article

Antimicrobial resistance is one of the drastically increasing major global health threats due to the misuse and overuse of antibiotics as traditional antimicrobial agents, which render urgent the need for alternative and safer antimicrobial agents, such as essential oils (EOs). Although the strong antimicrobial activity of various EOs has already been studied and revealed, their characteristic high sensitivity and volatility drives the need towards a more efficient drug administration method via a biomaterial system. Herein, the potential of Thymus sibthorpii EO incorporated in functionalized antibacterial collagen hydrogels was investigated. At first, the optimally stabilized type I collagen hydrogels via six different multi-arm poly (ethylene glycol) succinimidyl glutarate (starPEG) crosslinkers were determined by assessing the free amine content and the resistance to enzymatic degradation. Subsequently, 0.5, 1, and 2% v/v of EO were incorporated into optimized collagen hydrogels, and the release profile, as well as release kinetics, were studied. Finally, biomaterial cytocompatibility tests were performed. Thymus sibthorpii EO was released from the hydrogel matrix via Fickian diffusion and showed sustained release and 0.5% v/v EO-loaded hydrogels showed adequate antibacterial activity against Staphylococcus aureus and did not show any statistically significant difference compared to penicillin (p < 0.05). Moreover, none of the fabricated composite antibacterial scaffolds displayed any cytotoxicity on NIH-3T3 fibroblasts. In conclusion, this work presents an innovative antibacterial biomaterial system for tissue engineering applications, which could serve as a promising alternative to antibiotics, contributing to coping with the issue of antimicrobial resistance. Full article

Background/Objectives: Glioblastoma is the most common and lethal primary brain tumor. Patients often suffer from tumor- and treatment induced vasogenic edema, with devastating neurological consequences. Intracranial edema is effectively treated with dexamethasone. However, systemic dexamethasone requires large doses to surpass the blood brain barrier in therapeutic quantities, which is associated with significant side effects. The aim of this study was to investigate a biodegradable, dextran-hydroxyethyl methacrylate (dex-HEMA) based hydrogel, containing polymeric micelles loaded with dexamethasone and liposomes encapsulating dexamethasone phosphate for localized and prolonged delivery. Methods: Poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide (mPEG-b-p(HPMA-Bz)) micelles were loaded with dexamethasone and characterized. The dexamethasone micelles, together with dexamethasone phosphate liposomes, were dispersed in an aqueous dex-HEMA solution followed by radical polymerization using a photoinitiator in combination with light. The kinetics and mechanisms of drug release from this hydrogel were determined. Results: The diameter of the nanoparticles was larger than the mesh size of the hydrogel, rendering them immobilized in the polymer network. The micelles immediately released free dexamethasone from the hydrogel for two weeks. The dexamethasone phosphate loaded in the liposomes was not released until the gel degraded and intact liposomes were released, starting after 15 days. The different modes of release result in a biphasic and sequential release profile of dexamethasone followed by dexamethasone phosphate liposomes. Conclusions: The results show that this hydrogel system loaded with both dexamethasone polymeric micelles and dexamethasone phosphate loaded liposomes has potential as a local delivery platform for the sequential release of dexamethasone and dexamethasone phosphate, for the intracranial treatment of glioblastoma associated edema. Full article

Poly(lactic acid) (PLA) exhibits excellent shape memory properties but suffers from brittleness and a high glass transition temperature (T_g), limiting its utility in flexible and durable applications. This study explored the modification of PLA properties through the incorporation of poly(ethylene glycol) (PEG), varying in both content (5–20 wt%) and molecular weight (4000–12,000 g/mol), to enhance its suitability for specific applications, such as medical splints. The PLA/PEG blend, containing 15 wt% PEG and with a molecular weight of 12,000 g/mol, exhibited superior shape fixity (99.27%) and recovery (95.77%) in shape memory tests conducted at a programming temperature (T_p) of 45 °C and a recovery temperature (T_r) of 60 °C. Differential scanning calorimetry (DSC) analysis provided insights into the thermal mechanisms driving shape memory behavior of the PLA/PEG blend. The addition of PEG to the PLA blend resulted in a reduction in T_g and an increase in crystallinity, thereby facilitating enhanced chain mobility and structural reorganization. These thermal changes enhanced the shape fixity and recovery of the PLA/PEG blend. Synchrotron wide-angle X-ray scattering (WAXS) was further employed to elucidate the microstructural evolution of PLA/PEG blends during the shape memory process. Upon stretching, the PLA/PEG chains aligned predominantly along the tensile direction, reflecting strain-induced orientation. During recovery, the PLA/PEG chains underwent isotropic relaxation, reorganizing into their original configurations. This structural reorganization highlighted the critical role of chain mobility and alignment in driving the shape memory behavior of PLA/PEG blends, enabling them to effectively return to their initial shape. Mechanical testing confirmed that increasing PEG content and molecular weight enhanced elongation at break and impact strength, balancing flexibility and strength. These findings demonstrated that PLA/PEG blends, especially with 15 wt% PEG at 12,000 g/mol, offer an optimal combination of shape memory performance and mechanical properties, positioning them as promising candidates for customizable and biodegradable medical applications. Full article

As the demand for sustainable and innovative solutions in food packaging continues to grow, this study endeavors to introduce a comprehensive exploration of novel active materials. Specifically, we focus on characterizing polylactide-poly(ethylene glycol) (PLA/PEG) films filled with olive leaf extract (OLE; Olea europaea) obtained via solvent evaporation. Examined properties include surface structure, thermal degradation and mechanical attributes, as well as antibacterial activity. The results indicated a significant impact of the incorporation of OLE into this polymeric matrix, increasing hydrophobicity, decreasing surface free energy, and enhancing surface roughness, albeit with slight reductions in mechanical properties. Notably, these modified materials exhibited significant bacteriostatic, bactericidal and anti-adhesive activity against both Staphylococcus aureus and Escherichia coli. Consequently, PLA/PEG/OLE films demonstrated considerable potential for advanced food packaging, facilitating interactions between products and their environment. This capability ensures the preservation and extension of food shelf life, safeguards against microbial contamination, and maintains the overall quality, safety, and integrity of the packaged food. These findings suggest potential pathways for developing more sustainable and effective food packaging films. Full article