Search Results (568)

Postsurgical adhesions are common complications of abdominal and pelvic surgeries, often leading to bowel obstruction, chronic pain, and increased risks during reoperation. Although various physical barrier materials have been developed to prevent postsurgical adhesions, retaining anti-adhesive materials at surgical sites is challenging. In this study, we developed thermosensitive injectable gallic acid-conjugated hyaluronic acid (HA-GA) and Pluronic F127 (PluF) composite hydrogels to retain anti-adhesive materials and prevent postsurgical adhesion. The incorporation of HA-GA reduced the critical gelation concentration of PluF from approximately 18 to 12 wt% and decreased the gelation temperature from 28.5 °C for PluF to 25.6 °C for HA-GA (2 wt%)/PluF hydrogels with the left-shift in sol–gel curves. The G′ values increased from 10.1 ± 1.7 kPa for PluF to 24.8 ± 3.6 kPa for HA-GA (2 wt%)/PluF hydrogels at 37 °C. In addition, the HA-GA/PluF hydrogels exhibited enhanced mass retention as a function of time compared to PluF hydrogels alone. HA-GA (2 wt%)/PluF hydrogels retained 33.4 ± 3.5% of their initial mass after 7 d, whereas PluF was completely eroded within 3 d. The anti-adhesion efficacy of the HA-GA/PluF hydrogels was evaluated using a rat cecum abrasion model. Notably, the HA-GA (2 wt%)/PluF hydrogels showed reduced adhesion scores, with an adhesion extent score of 0.67 and 2.33 on postoperative day 7 and 21, respectively, compared with the untreated control group (3 and 3 on postoperative day 7 and 21). In addition, the adhesion severity scores of HA-GA (2 wt%)/PluF hydrogel groups were 0.33 and 1.33 on postoperative day 7 and 21, respectively, compared with the untreated control groups (1.67 and 2.33 on postoperative day 7 and 21). Therefore, HA-GA/PluF hydrogels provide reversible thermosensitive properties with enhanced stability and retention, supporting their potential as injectable physical barriers for postoperative adhesion prevention. Full article

Vaginal drug delivery offers a critical route for local treatments but is limited by short formulation residence times. This study describes a thermosensitive in situ gel prepared by the cold-dissolution method from a ternary blend of Pluronic F127, Carbopol 940, and HPMC for localized vaginal therapy. We used ibuprofen as a model drug selected for its reported anti-inflammatory and antiproliferative activity. The hydrogels exhibited a constant gelation temperature of 28 °C and high viscosity under simulated physiological conditions; ibuprofen incorporation further reduced susceptibility to gravitational leakage. FTIR, XRD, and DSC analyses confirmed stable physical cross-linking of the polymer network and amorphous molecular dispersion of ibuprofen. Peppas–Sahlin modelling revealed a controlled, sustained release profile (>50% over 24 h) predominantly governed by Fickian diffusion (69%). The blank hydrogel exhibited high biocompatibility (>75% viability). In contrast, the ibuprofen-loaded matrix exhibited a concentration-dependent cytotoxic effect on HeLa cervical cancer cells, reducing cell viability to ~12% at the full extract concentration. Overall, this ternary hydrogel platform represents a stable, promising vehicle for sustained local administration of ibuprofen in the vaginal microenvironment. Full article

Background/Objectives: The increasing therapeutic use of cannabinoid-based formulations highlights the need to better characterize their safety profile, particularly in organs involved in xenobiotic elimination, such as the kidneys. This study evaluated the renal effects of cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (Δ⁹-THC) nanoemulsions following subchronic oral administration in male Wistar rats. Methods: Forty animals (n = 8/group) were randomly allocated into five groups: vehicle control (Licuri oil + Pluronic^® F127), CBD 2.5 mg/kg, CBD 5 mg/kg, CBD+THC 2.5 mg/kg, and CBD+THC 5 mg/kg. Treatments were administered daily by oral gavage for 21 consecutive days. Kidney samples were analyzed by histopathology and immunohistochemistry (Ki-67, GST-P, and cleaved caspase-3). Results: High-dose groups (5 mg/kg) exhibited marked histopathological alterations, including tubular and glomerular damage, hemorrhagic areas, inflammatory infiltration, and necrosis. These groups also showed increased Ki-67 and cleaved caspase-3 immunoexpression compared to controls. GST-P expression was significantly increased only in the CBD 5 mg/kg group. No significant changes were observed in the low-dose groups. Conclusions: These findings suggest dose-dependent morphological and molecular alterations in renal tissue associated with cannabinoid nanoemulsion exposure under experimental conditions. Full article

Injectable thermoresponsive hydrogels are useful for localized drug delivery because they can be administered as low-viscosity formulations and then form, or reinforce, therapeutic depots directly at diseased tissue sites. Their common design principle is a temperature-dependent transition from a flowable formulation before administration to an in situ matrix at physiological temperature, or a thermally regulated change in swelling, mesh size, drug-matrix affinity or degradation. This review focuses on thermoresponsive injectable systems for localized delivery, including PNIPAM-based systems, poloxamers/Pluronics, PEG/polyester block copolymers, polyurethane-based hydrogels, chitosan-based thermogels, hyaluronan- and glycosaminoglycan-based systems, and selected multicomponent or nanocomposite networks. The in vivo application areas considered are local cancer therapy, wound healing and antibacterial treatment, osteoarthritis and intra-articular delivery, and myocardial infarction/cardiac repair. Across these indications, preclinical studies suggest that thermoresponsive hydrogels may prolong local residence time, reduce systemic exposure, enhance delivery of poorly soluble or unstable payloads, and modulate disease-specific microenvironments. Remaining challenges include gelation control, mechanical stability, degradation products, immune response, sterilization, manufacturing reproducibility, disease heterogeneity and robust translational validation. Full article

Nonlamellar liquid crystalline nanodispersions produced from single monoacylglycerols or from their combinations with fatty acids or other amphiphiles have attracted interest owing to their structural versatility and tunability. In this study, we investigated the effect of dilinolein (DLO) incorporation on the structural features of Pluronic F127-stabilized monolinolein (MLO) nanodispersions using small-angle X-ray scattering (SAXS), cryogenic transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS). We report a lipid composition-dependent direct colloidal transformation from hexosomes, defined as nanoparticles with an ordered internal inverse hexagonal (H₂) phase, toward nanoparticles with highly disordered internal nanostructures upon the partial replacement of MLO by DLO. Small-angle X-ray scattering (SAXS) measurements showed that, at relatively low DLO content, the MLO-rich MLO:DLO 90:10 (w/w) nanodispersion retained an ordered internal H₂ phase, with three well-defined characteristic Bragg peaks, whereas the SAXS patterns recorded for nanodispersions containing ≥20 wt% DLO displayed loss of the characteristic H₂ Bragg reflections and broad correlation maxima, indicating loss of long-range internal periodicity and the emergence of highly disordered internal nanostructures. Similarly, the control nanodispersion prepared from DLO alone displayed a broad, low-intensity correlation maximum rather than distinct Bragg peaks, consistent with a highly disordered internal nanostructure. For the nanodispersions displaying broad SAXS correlation maxima, the SAXS-derived characteristic distance decreased monotonically from 4.53 to 2.87 nm as the DLO fraction increased. Additional cryo-TEM observations of two nanodispersions containing relatively high DLO contents revealed predominantly spherical nanoparticles characterized by an intense lipid core and discernible internal nanoscale features. However, these internal features were not sufficiently resolved to allow full characterization and unambiguous assignment of the internal phase, consistent with a highly disordered inverse nanostructure that may include an L₂-like inverse-micellar organization alongside other possible arrangements such as nanoemulsion droplets. Taken together, the SAXS and cryo-TEM observations indicate a composition-driven colloidal transformation from hexosomes with a well-defined internal H₂ phase toward nanoparticles with a highly disordered internal phase as the DLO content increases. The experimental findings suggest that DLO modifies lipid packing at the MLO–water interface and promotes more negative spontaneous curvature, favoring the observed structural transformation. The ability to tune the internal nanostructure by lipid composition while maintaining nanoscale particle size and low dispersity makes these nanodispersions attractive platforms for drug nanocarrier development. Full article

Polyetherimide (PEI) ultrafiltration membranes were fabricated for bovine serum albumin (BSA) separation using nonsolvent-induced phase separation (NIPS) and vapor-induced phase separation (VIPS). In the NIPS approach, membranes containing varying amounts of Pluronic P-123, with or without graphene nanoplatelets (GNPs), were prepared. Pluronic P-123 acted as a pore-forming agent, while GNPs enhanced permeability without compromising rejection. The membrane with 1 wt.% Pluronic P-123 achieved a pure water flux (PWF) of 355 LMH and 90% BSA rejection. Incorporating 1 wt.% GNPs further improved performance to 747 LMH and 98% rejection. VIPS membranes were fabricated using the same composition as N10, containing 17 wt.% PEI and 1 wt.% Pluronic P-123 without GNPs, to isolate the effect of the fabrication pathway. Increasing vapor exposure time reduced PWF but generally improved BSA rejection, whereas higher RH increased PWF while decreasing rejection. The composition-matched NIPS membrane, N10, exhibited a PWF of 355 LMH and approximately 91% BSA rejection. In comparison, the highest PWF and BSA rejection among the VIPS membranes were 91 LMH and 76.5%, respectively, and the selected balanced VIPS condition at 30 min and 65% RH yielded approximately 49 LMH and 55% rejection. The higher performance of N11, which achieved 747 LMH and 98% rejection, is attributed to GNP incorporation within the NIPS series and was not used to isolate the fabrication-pathway effect. Overall, the composition-matched comparison demonstrates that NIPS produced a more favorable morphology and BSA separation performance than VIPS under the investigated conditions. Full article

Developing effective oral formulations for poorly soluble anticancer drugs remains a major pharmaceutical challenge due to the combined limitations of solubility, permeability, and efflux transporter activity. In this work, we investigated the influence of the nonionic surfactants Cremophor EL, Pluronic P-85, and Pluronic F-68 on the solubility and intestinal permeability of the anticancer drug etoposide. All surfactants significantly increased etoposide aqueous solubility. While in vitro permeability across an artificial membrane demonstrated the expected solubility-permeability tradeoff, in vivo SPIP studies in rats revealed a distinctive solubility-permeability interplay for Cremophor EL and Pluronic P-85, which simultaneously enhanced solubility and permeability, likely through P-gp inhibition. In contrast, Pluronic F-68 exhibited the classical solubility-permeability tradeoff, consistent with its reported negligible P-gp inhibitory activity. Mechanistic analysis indicated that surfactant hydrophobicity and molecular weight critically influence P-gp inhibition via ATPase modulation. Surfactants with higher hydrophobicity and moderate molecular weight can integrate into the phospholipid bilayer, enabling direct interaction with P-gp and disruption of its ATPase function. These findings provide strategic insights for the rational design of oral formulations capable of overcoming the solubility-permeability tradeoff, improving the bioavailability of challenging anticancer drugs, and may facilitate the transition from intravenous to oral chemotherapy. Full article

Background: Imperatorin (IPT) is a natural furanocoumarin featuring robust anti-inflammatory, antifibrotic and antioxidant activities. However, poor aqueous solubility and insufficient oral bioavailability restrict its clinical application. Multiple gastrointestinal barriers, including the mucus barrier, limited epithelial penetration and P-glycoprotein-triggered drug efflux, are major obstacles hindering IPT oral absorption. Methods: N-acetylcysteine (NAC)-functionalized TPGS conjugates were synthesized first. Using Pluronic^® F108 and Lipoid^® S-100 as a matrix, imperatorin@N-acetylcysteine-TPGS/Pluronic^® F108/Lipoid^® S-100 (IPT@NAC-TFS) micelles were fabricated. We characterized their physicochemical features and in vitro release behavior. The Caco-2/HT29-MTX-E12 co-culture cell model was adopted to explore mucus permeation, cellular uptake and transepithelial transport mechanisms. In vivo intestinal distribution and pharmacokinetic tests in rats were carried out to confirm the oral absorption-enhancing effect of micelles. Results: Optimized micelles displayed a uniform shape and favorable encapsulation efficiency. Low CMC maintained structural stability upon gastrointestinal dilution. NAC modification conferred mucus-penetrating capacity on micelles. TPGS simultaneously improved epithelial barrier permeability and inhibited drug efflux, switching IPT transport mode. The micelles effectively cleared intracellular ROS, recovered SOD activity and lowered MDA levels in BLM-impaired MLg fibroblasts. In vivo results revealed enhanced intestinal drug accumulation, with the relative oral bioavailability of IPT increased by 6.07-fold. Conclusions: IPT@NAC-TFS micelles overcome multiple gastrointestinal barriers for oral IPT delivery. Combining mucus penetration, efflux suppression and antioxidative capacity, this system offers a promising strategy to develop oral formulations of poorly soluble antifibrotic natural products. Full article

Background: Poor aqueous solubility of therapeutic molecules remains a limitation in the pharmaceutical development of lipophilic drugs. This requires formulation approaches that provide the desired therapeutic efficacy while being industry-friendly. This study aimed to optimize a thermoresponsive solid dispersion containing atorvastatin calcium to enhance its dissolution performance. Methods: Various nonaqueous solvents were screened to select a thermo-modulating agent. A central composite design was employed to investigate the impact of Pluronic F-68 concentration (5–15% w/w) and atorvastatin calcium concentration (5–10% w/w) on phase transition temperature and phase transition interval. Molecular interactions were assessed by Fourier-transform infrared spectroscopy. The in vitro dissolution of the optimized thermoresponsive solid dispersion was assessed using a USP Apparatus II dissolution test. Results: Propylene glycol was identified as the optimal thermo-modulating agent, forming a rigid carrier through hydrogen bonding with Pluronic F-68. The optimized thermoresponsive solid dispersion consisted of 10.07% w/w Pluronic F-68 and 9.98% w/w atorvastatin calcium. It converted to a solution state at 32 °C. At physiological temperature, the phase transition interval was 111.66 s. Dissolution studies demonstrated that the thermoresponsive solid dispersion enhanced the dissolution profile of atorvastatin calcium within 5 min, 96.6 ± 1.2% compared to 13.8 ± 4.2% for the raw drug. A comparison of process characteristics indicated fewer unit operations and no organic-solvent requirement relative to conventional techniques. Conclusions: This approach enhances dissolution performance and eliminates the need for organic solvents through simple manufacturing processes. Full article

Recurrent urinary tract infection (rUTI) continues to pose a formidable clinical challenge, largely owing to the rapid clearance of therapeutic agents from the bladder caused by short intravesical residence time and periodic urinary voiding. Although intravesical drug delivery has emerged as a promising local therapeutic strategy, conventional liquid instillations and physically crosslinked hydrogels frequently fail to sustain structural integrity and prolonged drug release within the dynamically changing bladder microenvironment. Herein, we develop a photocrosslinkable, pH-responsive intravesical floating drug delivery system (iFDDS) for sustained antimicrobial delivery. This system is fabricated using diacrylated Pluronic F127 (F127DA) as the core network-building component. The covalently crosslinked F127DA network confers superior mechanical stability while preserving amphiphilic micellar domains that enable efficient loading of hydrophobic drugs. A tertiary amine-based pH-responsive crosslinker (CLMA) is further integrated into the hydrogel matrix, endowing iFDDS with enhanced swelling capacity under the mildly acidic microenvironment. Additionally, lyophilization-induced porous architecture reduces the apparent density of the iFDDS below that of urine, achieving stable flotation for over 48 h and effectively mitigating the risk of urinary tract obstruction. The optimized iFDDS exhibits favorable catheter deliverability, shear-thinning rheological behavior adaptable to dynamic fluid conditions, and excellent biocompatibility with bladder epithelial cells. Upon loading with rifampicin, the iFDDS demonstrates potent and sustained antibacterial efficacy against Escherichia coli. This study establishes a robust, environment-adaptive platform for intravesical therapy, offering a viable strategy to address the short residence time limitation of conventional formulations and improve the therapeutic management of rUTI. Full article

Encapsulation of resveratrol (RVT), a natural polyphenol, in mixed Pluronic F127/P123 micelles (mRVT) has enhanced its pharmacological efficacy in experimental dementia models. The aim of this study was to evaluate neurochemical and behavioral parameters of mRVT treatment in healthy subjects. For this purpose, pure RVT and mRVT (both at 10 mg/kg i.p.) were applied for 9 consecutive days in healthy male Wistar rats. Memory performance was assessed using the novel object recognition and passive avoidance tests. Neurotransmitter levels, neurotrophic and transcription factors, and oxidative stress markers were quantified in the cortex and hippocampus using enzyme-linked immunosorbent assay kits. Our results showed that neither treatment altered locomotor activity or short-term memory performance. Both RVT and mRVT treatments reduced hippocampal acetylcholinesterase activity to a similar extent and elevated acetylcholine levels in the cortex and hippocampus, with mRVT producing significantly more pronounced effect in the hippocampus. Compared to pure RVT, mRVT elicited a greater increase in noradrenaline and serotonin levels in both brain regions and comparably upregulated BDNF and pCREB protein levels in the cortex. Furthermore, mRVT uniquely reduced cortical lipid peroxidation—an effect absent with pure RVT treatment. These findings demonstrate that micellar encapsulation substantially amplifies the neurochemical efficacy of resveratrol under physiological conditions without adverse behavioral effects. Full article

Subretinal and intravitreal injection of retinal gene therapy is associated with serious adverse events and poor efficacy. We sought to improve retinal gene therapy delivery by developing fibrin hydrogel encapsulated adeno-associated virus (FE-AAV). Here we investigate conditions for storage and stability for FE-AAV. FE-AAV containing 1.9 × 10⁹ genome copies of AAV2/2-CMV-GFP was manufactured using fibrinogen reconstituted in 0.01 M sodium citrate, pH 7 (NaC) or phosphate-buffered saline containing 0.001% (v/v) Pluronic F68 (F68). Samples were stored at either −80 °C or 4 °C for up to 16 weeks. Changes in transduction efficiency, and mechanical and physical properties were evaluated. In vitro transduction was significantly (p < 0.05) reduced for FE-AAV manufactured with NaC. In contrast, we observed no change in transduction through 16 weeks for FE-AAV made with F68. Physical changes occurred in FE-AAV stored at −80 °C. In contrast to FE-AAV formulated with NaC, FE-AAV formulated with F68 and stored at 4 °C for 16 weeks was essentially equivalent to freshly made FE-AAV and retained the ability to transduce retinal pigment epithelial (RPE) cells in the pig eye. We conclude that FE-AAV formulated with F68 and stored at 4 °C is stable and shows potential for retinal gene therapy for at least 4 months following manufacture. Full article

Donor–acceptor (D–A) molecular systems are gaining increasing attention in cancer imaging and phototherapy due to their tunable optical properties and high photosensitizing efficiency. Encapsulation of such D–A molecules in nano-sized polymeric carriers can enhance the efficiency of antitumor therapy by passive tumor accumulation and controlled drug release. Here, we synthesized two D–A molecules—TTDCV and TTInd—based on triphenylamine with thiophene π-spacers and electron-withdrawing dicyanovinyl or indene-1,3-dione moieties. These molecules were used to preparate nanoparticles (NPs) via nanoprecipitation with amphiphilic polymers—poly(ethylene glycol)-block polylactide methyl ether (PEG-b-PLA) and polyethylene oxide-polypropylene oxide (PEO-PPO-PEO, Pluronic^® F-127). The resulting NPs had spherical morphology, core–shell structure and a tunable mean size (66–139 nm), depending on the polymer type used. Photothermal and photodynamic properties of the NPs were confirmed by intracellular reactive oxygen species generation and efficient heating even under 530 nm low dose irradiation (1 J/cm²), leading to substantial in vitro cytotoxicity against Sk-Br-3 and MCF-7 human breast cancer cells. Pluronic-encapsulated systems showed the strongest effect, reducing IC₅₀ values down to 0.99 µg/mL and achieving phototoxicity indices up to 22, accompanied by increased intracellular accumulation studied by confocal microscopy and flow cytometry. This study establishes relationships between molecular design, encapsulation approaches, and the biological performance of nanoparticles, enabling the rational engineering of D–A-derived nanotherapeutics for precision cancer treatment. Full article

Monitoring ultraviolet (UV) radiation dose distribution is crucial in many fields, like medicine and materials science, but traditional point-of-care methods limit the ability to fully assess the spatial extent of the irradiated surface. This paper presents the characterisation of a two-dimensional (2D) dosimetry system based on Pluronic F-127 hydrogel matrix doped with 2,3,5-triphenyltetrazolium chloride (TTC) with respect to exposition to UVA radiation. The hydrogel matrix (25% w/w) provides both high transparency and mechanical stability, while TTC (0.1% w/w) functions as a colour precursor that undergoes irreversible reduction to form water-insoluble red formazan upon UVA exposure. The insolubility of TTC formazan ensures that the resulting colour changes remain spatially stable within the dosimeter. The study included sample preparation in flat PMMA containers and analysis of the effect of radiation field uniformity in a UVP CL-1000 exposure chamber. It was supported by application of Kodak X-Omat 100 NIF UV Film dosimetry. The actual dose distribution in the chamber was shown to be significantly heterogeneous (CV coefficient of variation of approximately 18%), which emphasises the need for 2D dosimeters for precise validation of irradiation devices. The use of flatbed scanning and dedicated image analysis software allowed obtaining precise 2D dose distribution maps. The dosimeter was characterised in the dose range of 0–5000 mJ/cm², showing a reproducible response (R² = 0.9967). A resolution test was conducted to assess the precision of geometric representation. In the final stage of the study, the suitability of the developed dosimetry system was verified under conditions simulating heterogeneous UV radiation dose distribution using patterns printed with Computer-to-Film (CtF) technology. The results showed that optical effects in printed films significantly affect UV transmission, limiting accurate dose recording for black coverage above approximately 40–50%. The results obtained confirm that the TTC-Pluronic F-127 system is an effective, simple and low-cost tool for 2D monitoring of UVA radiation, with potential applications in cosmetology, dermatology, and material ageing tests. Full article

The natural stilbene resveratrol is a widely researched molecule, owing to its antioxidant activity and abundance of pharmacological effects. However, its application is still hindered due to its low aqueous solubility, bioavailability and photostability. Therefore, in the current study, resveratrol was loaded in two types of polymeric nanoparticles, namely mixed Pluronic F127 and P123 micelles, and bovine serum albumin nanospheres. The loaded micelles and nanospheres possessed mean diameters of 33 nm and 145 nm, zeta potentials of −4 mV and −22.6 mV, and encapsulation efficiency levels of 89.4% and 76.2%, respectively. The aqueous solubility of resveratrol increased after loading, especially in the albumin nanospheres. A sustained release was observed, more pronounced for the micelles. The photostability of the encapsulated and pure resveratrol was evaluated under daylight exposure and UV irradiation. The micelles showed superior protective effect compared to the nanospheres. The antioxidant potentials of the formulations were examined through ABTS radical scavenging activity assay and in vitro cell model of oxidative stress in L929 fibroblasts. The resveratrol-loaded albumin nanospheres showed a more enhanced antioxidant effect. Thus, the encapsulation of resveratrol in both types of nanoparticles could be considered an advantageous approach due to improvements in solubility, stability and antioxidant activity. Full article