Search Results (89)

Background/Objectives: The intranasal (IN) route of administration is a promising non-invasive approach for brain targeting, bypassing the blood–brain barrier and enhancing bioavailability. Citalopram hydrobromide (CT), a widely prescribed sparingly water-soluble selective serotonin reuptake inhibitor (SSRI), faces challenges with oral and intravenous administration, including delayed onset, adverse effects, and patient compliance issues. Methods: This study aimed to develop a novel thermoresponsive polymeric micelle (PM) system based on Pluronic^® copolymers (Pluronic F127 and Poloxamer 188) improving CT’s solubility, stability, and nasal permeability for enhanced antidepressant efficacy. A preliminary study was conducted to select the optimized formulation. The preparation process involved using the thin-film hydration method, followed by freeze-drying. Comprehensive evaluations of optimized formulation characteristics included Z-average, polydispersity index (PdI), thermal behavior (lower critical solution temperature, LCST), encapsulation efficiency, X-ray powder diffraction (XRPD), thermodynamic solubility, and biological stability. Additionally, in vitro CT release and CT permeability in nasal conditions were studied. Stability under storage was also evaluated. Results: The optimized CT-PM formulation showed nanoscale micelle size (Z-average of 31.41 ± 0.99 nm), narrow size distribution (polydispersity index = 0.241), and a suitable thermal behavior for intranasal delivery (lower critical solution temperature (LCST) ~31 °C). Encapsulation efficiency reached approximately 90%, with an amorphous structure confirmed via XRPD, leading to a 95-fold increase in CT solubility. The formulation demonstrated appropriate biological and physical stability. In vitro studies showed a 25-fold faster CT release from optimized formulation compared to the initial CT, while CT-PM permeability in nasal conditions increased four-fold. Conclusions: This novel nanoscale thermosensitive formulation is a value-added strategy for nasal drug delivery systems, offering enhanced drug solubility, rapid drug release, stability, and improved permeability. This smart nanosystem represents a promising platform to overcome the limitations of conventional CT administration, improving therapeutic outcomes and patient compliance in depression management. Full article

This study aimed to develop and evaluate a bakuchiol-loaded thermosensitive hydrogel (BTH) as a novel local drug delivery system for the management of periodontitis. Bakuchiol, a natural phenolic compound extracted from Psoralea corylifolia, was incorporated into a hydrogel composed of poloxamers and carboxymethylcellulose. The gelation behavior, physicochemical properties, and drug release profile were analyzed. Additionally, antibacterial activity against Porphyromonas gingivalis was assessed. Cytotoxicity was evaluated in human gingival fibroblasts and RAW 264.7 cells. Anti-inflammatory effects were determined by measuring proinflammatory cytokine expression in lipopolysaccharide-stimulated RAW 264.7 macrophages. Furthermore, alveolar bone loss, cytokine expression, and histological findings were assessed in a rat model of ligature-induced periodontitis. BTH demonstrated sol–gel transition at body temperature, with sustained drug release over 15 days. Moreover, it exhibited significant antibacterial activity against P. gingivalis and was non-cytotoxic at an extract concentration of 6.25%. In vitro, it significantly downregulated inflammatory cytokines in activated macrophages. In vivo, BTH application reduced alveolar bone loss and interleukin-1β expression in gingival tissues. Histological analysis confirmed decreased inflammatory cell infiltration and alveolar bone destruction. Thus, BTH demonstrated both antibacterial and anti-inflammatory activities, exhibiting potential as a promising therapeutic strategy for localized periodontal treatment. Full article

Background/Objectives: Cirsium setosum (commonly known as thistle) is a traditional Chinese medicinal plant with significant therapeutic potential, exhibiting hemostatic, antioxidant, and wound-healing properties. Electrospinning offers a versatile platform for fabricating nanoscale scaffolds with tunable functionality, making them ideal for drug delivery and tissue engineering. Methods: In this study, a bioactive extract from thistle was obtained and incorporated into a thermosensitive triblock copolymer (PNNS) and polycaprolactone (PCL) to develop a multifunctional nanofibrous scaffold for enhanced wound healing. The prepared nanofibers were thoroughly characterized using Fourier-transform infrared spectroscopy (FTIR), contact angle measurements, thermogravimetric analysis (TGA), and tensile fracture testing to assess their physicochemical properties. Results: Notably, the inclusion of PNNS imparted temperature-responsive behavior to the scaffold, enabling controlled deformation in response to thermal stimuli—a feature that may facilitate wound contraction and improve scar remodeling. Specifically, the scaffold demonstrated rapid shrinkage at a physiological temperature (38 °C) within minutes while maintaining structural integrity at ambient conditions (20 °C). In vitro studies confirmed the thistle extract’s potent antioxidant activity, while in vivo experiments revealed their effective hemostatic performance in a liver bleeding model when delivered via the composite nanofibers. Thistle extract and skin temperature-responsive contraction reduced the inflammatory outbreak at the wound site and promoted collagen deposition, resulting in an ideal wound-healing rate of above 95% within 14 days. Conclusions: The integrated strategy that combines mechanical signals, natural extracts, and electrospinning nanotechnology offers a feasible design approach and significant technological advantages with enhanced therapeutic efficacy. Full article

Background: Spinal cord injury (SCI) is a devastating neurological condition with limited therapeutic options. Current clinical interventions predominantly rely on prolonged or high-dose pharmacological regimens, often causing systemic toxicity and adverse events. Although black phosphorus nanosheets (BPNSs) exhibit remarkable reactive oxygen species (ROS)-scavenging capacity to mitigate oxidative damage, their rapid degradation severely compromises their therapeutic efficacy. Methods: This study presents a thermosensitive hydrogel with rapid gelation properties by incorporating different proportions and concentrations of sodium alginate (SA) into a chitosan/β-glycerophosphate (CS/β-GP) hydrogel and loading it with BPNS for the treatment of SCI in rats. In vitro, the physical properties of the composite were characterized and the cytotoxicity and ROS scavenging abilities were assessed using PC12 cells; in vivo, behavioral tests, histopathological analysis, transcriptomics, immunohistochemistry, and Western blotting were performed to explore the therapeutic effects and mechanisms. Results: The results demonstrate that this hydrogel effectively slows BPNS degradation, exhibits a high ROS scavenging capacity, reduces lipid peroxidation, and thereby inhibits ferroptosis and apoptosis, offering neuroprotective effects and promoting motor function recovery. Conclusions: Our findings establish the CS/β-GP/SA-BPNS hydrogel as a multifunctional therapeutic platform for SCI, synergizing sustained drug release with ROS–ferroptosis–apoptosis axis modulation to achieve neuroprotection and functional restoration. This strategy provides a translatable paradigm for combining nanotechnology and biomaterial engineering in neural repair. Full article

Chitosan (CS), a versatile biopolymer obtained through the deacetylation of chitin, has gained significant interest in biomedical and pharmaceutical applications due to its biocompatibility, biodegradability, and unique gel-forming capabilities. This review comprehensively analyzes CS-based gel development, covering its extraction from various natural sources, gelation mechanisms, and biomedical applications. Different extraction methods, including chemical, biological, and green techniques, are discussed regarding efficiency and sustainability. The review explores the physicochemical properties of CS that influence its gelation behavior, highlighting various gelation mechanisms such as physical, ionic, and chemical cross-linking. Recent advances in gel formation, including Schiff base reactions, Diels–Alder click chemistry, and thermosensitive gelation, have expanded the applicability of CS hydrogels. Furthermore, CS-based gels have demonstrated potential in wound healing, tissue engineering, drug delivery, and antimicrobial applications, offering controlled drug release, enhanced biocompatibility, and tunable mechanical properties. The incorporation of nanomaterials, bioactive molecules, and functional cross-linkers has further improved hydrogel performance. The current review underscores the growing significance of CS-based gels as innovative biomaterials in regenerative medicine and pharmaceutical sciences. Full article

The stability of cement slurries under high-temperature conditions poses a significant engineering challenge in cementing operations. This study explored the development of a novel tetrameric thermosensitive thickening polymer (TTSTC) as a solution to this problem. Aqueous free radical polymerization was employed to synthesize the polymer. The base monomers 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and acrylamide (AM) were employed, in conjunction with the long-chain thermosensitive monomers octadecyldimethylallylammonium chloride (C18DMAAC) and N-vinylpyrrolidone (NVP). The optimal synthesis conditions were determined by orthogonal experiments as follows: monomer molar ratio (AM:AMPS:C18DMAAC:NVP) = 15:10:5:5, initiator concentration of 16 wt%, cross-linker concentration of 0.45 wt%, pH 6, and polymerization temperature of 60 °C. The chemical structure of TTSTC was characterized by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H-NMR), gel permeation chromatography, scanning electron microscopy, Zeta potential, and particle size measurement. The results verified the successful synthesis of the target polymer. Its thermal stability, thermosensitive thickening behavior, and salinity resistance were systematically investigated. Furthermore, the impact of TTSTC on the settling stability, rheological characteristics, and compressive strength of cement paste was assessed. The experimental findings demonstrated that TTSTC displayed noteworthy thermosensitive thickening properties at temperatures up to 279 °C, pH values ranging from 11 to 13, and NaCl/CaCl₂ concentrations between 0.05 and 0.5 g/L. The optimal performance of TTSTC was observed at mass fractions ranging from 0.6 to 0.8 wt%. When incorporated into the slurry at 0.6–1.0 wt%, TTSTC significantly improved the slurry settling stability, thickening properties, and 28d compressive strength at elevated temperatures compared with the control. When comparing the temperature-sensitive thickening performance of the newly developed treatment agent with that of the commercially available xanthan gum thickener, the results showed that for the cement slurry system containing the new treatment agent at a mass fraction of 0.6%, the reduction in consistency was 30.9% less than that of the cement slurry system with xanthan gum at a mass fraction of 0.6%. These findings indicate that TTSTC has the potential to function as a highly effective additive in cementing operations conducted in extreme environments, thereby enhancing the stability and dependability of such operations. Full article

Background/Objectives: Neglected tropical diseases (NTDs), such as leishmaniasis, remain a global health challenge due to limited therapeutic options and rising drug resistance. In this study, we developed an advanced nanogel formulation incorporating curcumin (CUR) and Pectis brevipedunculata essential oil (EOPb) within an F127/Carbopol 974P matrix to enhance bioavailability and therapeutic efficacy against Leishmania (Leishmania) amazonensis (LLa) promastigotes. Methods: The chemical profile of EOPb was determined through GC-MS and NMR analyses, confirming the presence of key bioactive monoterpenes such as neral, geranial, $\alpha$-pinene, and limonene. The nanogel formulation (nGPC) was optimized to ensure thermosensitivity, and stability, exhibiting a sol–gel transition at physiological temperatures. Rheological analysis revealed that nGPC exhibited Newtonian behavior at 5 °C, transitioning to shear-thinning and thixotropic characteristics at 25 and 32 °C, respectively. This behavior facilitates its application and controlled drug release, making it ideal for topical formulations. Dynamic light scattering (DLS) analysis demonstrated that nGPC maintained a stable nanoscale structure with hydrodynamic radius below 300 nm, while Fourier-transform infrared spectroscopy (FTIR) confirmed strong molecular interactions between EOPb, CUR, and the polymer matrix. Biological assays demonstrated that nGPC significantly enhanced anti-promastigote activity compared to free CUR and OEPb. Results: At the highest tested concentration (50 μg/mL EOPb and 17.5 μg/mL CUR) nGPC induced over 88% mortality in LLa promastigotes across 24, 48, and 72 h, indicating sustained efficacy. Even at lower concentrations, nGPC retained dose-dependent activity, suggesting a synergistic effect between CUR and EOPb. These findings highlight the potential of nGPC as an innovative nanocarrier for daylight photodynamic therapy (dPDT) in the treatment of leishmaniasis. Future studies will investigate the underlying mechanisms of this synergism and explore the potential application of photodynamic therapy (PDT) to further enhance therapeutic outcomes. Full article

Many antifungal agents, including isoconazole nitrate (ISN), suffer from low aqueous solubility and inconsistent dissolution kinetics, which limit their therapeutic potential. To address these challenges, this study aimed to enhance the solubility and stability of ISN through the development of inclusion complexes with hydroxypropyl-β-cyclodextrin (HP-β-CD). HP-β-CD inclusion complexes were prepared using a spray-drying technique and characterized through phase-solubility studies, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (¹H-NMR), and differential scanning calorimetry (DSC). The inclusion complex significantly improved ISN solubility, increasing from 0.5088 mg/mL to 3.6550 mg/mL. These complexes were incorporated into a thermosensitive, mucoadhesive in situ gel system using Pluronic^® F127 and hydroxypropyl methylcellulose (HPMC) to optimize vaginal drug delivery. The formulations were evaluated for gelation temperature, viscosity, swelling behavior, and pH, confirming their suitability for vaginal application. Antimicrobial studies demonstrated that the ISN/HP-β-CD gels exhibited superior activity against Candida albicans, C. glabrata, and C. krusei compared to ISN alone. In vitro release studies further revealed sustained drug release following Peppas-Sahlin kinetics, supporting enhanced bioavailability and prolonged therapeutic action. This study demonstrates that the ISN/HP-β-CD-loaded in situ gel system offers a promising and effective approach for improving the solubility, stability, and antifungal efficacy of ISN for the treatment of vaginal infections. Full article

The synthesis of poly(N-isopropyl acrylamide) (pNIPA)-based polymers via the surfactant-free precipitation polymerization (SFPP) method produced thermosensitive nanospheres with a range of distinctive physicochemical properties. Nano- and microparticles were generated using various initiators, significantly influencing particle characteristics, including the hydrodynamic diameter (D_H), which varied from 87.7 nm to 1618.1 nm. Initiators, such as potassium persulfate and 2,2′-azobis(2-methylpropionamidine) dihydrochloride, conferred anionic and cationic functionalities, respectively, impacting the electrokinetic potential (EP) of the particles. Notably, certain particles with cationic initiators exhibited negative EP values at 18 °C, attributed to residual initiator components that affected the surface charge distribution. The presence of hydrophilic N-(2-hydroxyethyl)acrylamide (HEAA) segments also influenced solubility and phase transition behaviors, with critical dependencies on the HEAA/NIPA (N-isopropyl acrylamide) molar ratios. EP measurements taken at 18 °C and 42 °C revealed substantial differences, primarily governed by the initiator type and polymer composition. Observed variations in particle stability and size were associated with the choice of crosslinking agents and comonomer content, which affected both D_H and EP in distinct ways. This study provides insights into key factors influencing colloidal stability and electrostatic interactions within thermosensitive polymer systems, underscoring their potential applications in biomedical and industrial fields. Full article

The present study synthesized silver nanoparticles supported on a thermosensitive polymer with a core–shell structure, formed by a polystyrene (PS) core and a poly(N-isopropylacrylamide) (PNIPAM)/Poly(N, N-methylenebisacrylamide) (MBA) shell. The PS core was synthesized via semicontinuous heterophase polymerization at a flow of 0.073 g/min, enabling polystyrene nanoparticles with an average size (Dz) of 35.2 nm to be obtained. In the next stage, the conditions required for polymerization synthesis were established in seeded microemulsion using PS nanoparticles as seed and semicontinuously adding the thermosensitive shell monomer (PNIPAM/MBA) under monomer-flooded conditions to favor shell formation. The non-homopolymerization of PNIPAM/MBA was demonstrated by obtaining nanoparticles with a core–shell structure, with average particle sizes of 41 nm and extremely low and narrow polydispersity index (PDI) values (1.1). The thermosensitive behavior was analyzed by QLS, revealing an average shrinkage of 4.03 nm and a percentage of shrinkage of 23.7%. Finally, silver nanoparticles were synthesized on the core–shell heat-sensitive nanoparticles in a colloidal solution containing the latices, while silver nanoparticles were anchored onto the cross-linked heat-sensitive network via the formation of complexes between the Ag+ ions and the nitrogen contained in the PNIPAM/MBA network, favoring anchorage around the network and maintaining a size of 5 nm. Full article

Background/Objectives: Chronic skin wounds (CSWs) are a worldwide healthcare problem with relevant impacts on both patients and healthcare systems. In this context, innovative treatments are needed to improve tissue repair and patient recovery and quality of life. Cord blood platelet lysate (CB-PL) holds great promise in CSW treatment thanks to its high growth factors and signal molecule content. In this work, thermo-sensitive hydrogels based on an amphiphilic poly(ether urethane) (PEU) were developed as CB-PL carriers for CSW treatment. Methods: A Poloxamer 407^®-based PEU was solubilized in aqueous medium (10 and 15% w/v) and added with CB-PL at a final concentration of 20% v/v. Hydrogels were characterized for their gelation potential, rheological properties, and swelling/dissolution behavior in a watery environment. CB-PL release was also tested, and the bioactivity of released CB-PL was evaluated through cell viability, proliferation, and migration assays. Results: PEU aqueous solutions with concentrations in the range 10–15% w/v exhibited quick (within a few minutes) sol-to-gel transition at around 30–37 °C and rheological properties modulated by the PEU concentration. Moreover, CB-PL loading within the gels did not affect the overall gel properties. Stability in aqueous media was dependent on the PEU concentration, and payload release was completed between 7 and 14 days depending on the polymer content. The CB-PL-loaded hydrogels also showed biocompatibility and released CB-PL induced keratinocyte migration and proliferation, with scratch wound recovery similar to the positive control (i.e., CB-PL alone). Conclusions: The developed hydrogels represent promising tools for CSW treatment, with tunable gelation properties and residence time and the ability to encapsulate and deliver active biomolecules with sustained and controlled kinetics. Full article

Temperature is an essential physical characteristic that influences all biological processes. Building on previous research on dialkylamino-functionalized rhodamine-based thermo-sensors, we investigate herein the thermosensitive properties of triamino-phenazinium dyes. Through a simple five-step synthetic route, we synthesized amino-phenazinium chromophores 6 and 7, featuring diethylamine substituents at different positions. A comparative analysis of optical properties and thermosensitivity was conducted on these compounds and an isomer, 5, in which butylamine moiety replaced the diethylamine group. The different emissive behaviors of the three fluorophores emphasize that not only the chemical nature but also the specific position of the alkylamine substituent play fundamental roles in the synthesis of highly emissive thermo-probes. Full article

The fractal characterization of supported nanoparticles is a useful tool for obtaining structural and morphological information that strongly impacts catalytic properties. We have synthesized and characterized Pt supported on TiO₂ nanostructures. Triblock copolymers with thermosensitive properties were used as templating agents during the synthesis process. In addition to the several techniques used for the characterization of the materials, we carried out fractal analysis. The prepared materials showed a reduction in the band gap of TiO₂ from 3.44 to 3.01 eV. The extended absorption in the 500–700 nm regions is mostly attributed to the presence of supported Pt nanoparticles. The ability of the nanostructured Pt/TiO₂ catalysts to generate H₂ in an aqueous solution was evaluated. The test reaction was carried out in the presence of methanol, as a hole scavenger, under simulated solar light. Pt/TiO₂-3TB shows the highest rate of H₂ (4.17 mmol h⁻¹ g_cat⁻¹) when compared to Pt/TiO₂-0TB (3.65 mmol h⁻¹ g_cat⁻¹) and Pt/TiO₂-6TB (2.29 mmol h⁻¹ g_cat⁻¹) during simulated solar light irradiation. Pt/TiO₂-3TB exhibits a more structured organization (fractal dimensions of 1.65–1.74 nm at short scales, 1.27–1.30 nm at long scales) and a distinct fractal behavior. The generation of hydrogen via photocatalysis can be linked to the fractal characteristics. Full article

The objective of the study was to develop a novel topical gel by mixing Potentilla tormentilla ethanolic extract, thermosensitive poloxamer 407, and carbomer 940 and evaluating its stability and rheological behavior. The irritation potential of the gel was evaluated in accordance with the Organization for Economic Cooperation and Development Guidelines 404. The potential anti-inflammatory effects of the developed gel were evaluated in vivo in rats using the carrageenan-induced paw edema test. Moreover, the in silico binding affinity for chlorogenic and ellagic acid, as dominant components in the extract, against cyclooxygenase (COX) 1 and 2 was also determined. Our findings suggest that the gel containing Potentilla tormentilla extract remained stable throughout the observation period, exhibited pseudoplastic behavior, and caused no irritation in rats, thus being considered safe for topical treatment. Additionally, the developed gel showed the capability to reduce rat paw edema, which highlights significant anti-inflammatory potential. In silico analysis revealed that chlorogenic and ellagic acid exhibited a reduced binding affinity against COX-1 but had a similar inhibitory effect on COX-2 as flurbiprofen, which was confirmed by molecular dynamics results. The study proposes the possible application of Potentilla tormentilla ethanolic extract gel for the alleviation of localized inflammatory diseases; however, future clinical evaluation is required. Full article

Nebivolol hydrochloride (NEB), a 3rd-generation beta-blocker, was recently explored in managing open-angle glaucoma due to its mechanism of action involving nitric oxide release for the vasodilation. To overcome the issue of low ocular bioavailability and the systemic side effects associated with conventional ocular formulation (aqueous suspension), we designed and optimized polycaprolactone polymeric nanoparticles (NEB-PNPs) by applying design of experiments (DoE). The particle size and drug loading of the optimized NEB-PNPs were 270.9 ± 6.3 nm and 28.8 ± 2.4%, respectively. The optimized NEB-PNPs were suspended in a dual-sensitive in situ gel prepared using a mixture of P407 + P188 (as a thermo-sensitive polymer) and κCRG (as an ion-sensitive polymer), reported previously by our group. The NEB-PNPs-loaded in situ gel (NEB-PNPs-ISG) formulation was characterized for its rheological behavior, physical and chemical stability, in vitro drug release, and in vivo efficacy. The NEB-PNPs-loaded in situ gel, in ocular pharmacokinetic studies, achieved higher aqueous humor exposure (AUC_0–t = 329.2 ng × h/mL) and for longer duration (mean residence time = 9.7 h) than compared to the aqueous suspension of plain NEB (AUC_0–t = 189 ng × h/mL and mean residence time = 6.1 h) reported from our previous work. The pharmacokinetic performance of NEB-PNPs-loaded in situ gel translated into a pharmacodynamic response with 5-fold increase in the overall percent reduction in intraocular pressure by the formulation compared to the aqueous suspension of plain NEB reported from our previous work. Further, the mean response time of NEB-PNPs-loaded in situ gel (12.4 ± 0.6 h) was three times higher than aqueous suspension of plain NEB (4.06 ± 0.3 h). Full article