Search Results (499)

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

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

Gel-based novel drug delivery systems (NDDS) occupy a mechanistically distinct niche among controlled-release platforms because they decouple three design variablesnetwork cross-link density, continuous-phase polarity, and stimulus sensitivitythat in particulate carriers (liposomes, polymeric nanoparticles) are often interdependent. This critical review synthesizes 102 primary and secondary sources published predominantly between 2010 and 2026 to interrogate, rather than merely catalog, how hydrogels, organogels, aerogels, nanogels, in situ gelling systems, and hydrogel-forming microneedles have been engineered for site-specific pharmacotherapy. Beyond a taxonomic overview, the review quantitatively contrasts formulation parameters sol–gel transition temperatures (typically 32–37 °C for poloxamer 407/188 systems), swelling ratios, mesh sizes, and reported drug-release half-lives across oncology, chronic diabetic wound care, ophthalmic and nasal-to-brain delivery, musculoskeletal (intra-articular) therapy, subunit vaccine depots, periodontal pocket therapy, and glucose-responsive insulin delivery. Particular attention is paid to the mechanistic basis of burst release, the porosity–mechanical-integrity trade-off inherent to interconnected hydrogel networks, and the divergence between preclinical rodent efficacy and the comparatively sparse controlled human trial data available for most gel platforms. The review concludes that while stimuli-responsive and 3D/4D-printed gel architectures have matured substantially as engineering constructs, clinical translation remains bottlenecked less by materials science than by inconsistent characterization standards, unresolved terminal-sterilization compatibility, and a paucity of head-to-head comparative trials against existing standard-of-care formulations. Full article

Background/Objectives: The aim of this study was to develop and validate a simple, accurate, reproducible, and sensitive reverse-phase high-performance liquid chromatography method for the quantification of reproxalap (RP) in cyclodextrin (CD) inclusion complexes and poloxamer 407 hydrogel formulations. Methods: Chromatographic separation was achieved using a mobile phase of deionized water and an organic phase (methanol:acetonitrile, 55:45 v/v) in a 40:60 (v/v) ratio, at a flow rate of 0.9 mL/min and a run time of 10 min. Validation assessed linearity, specificity, accuracy, and sensitivity over a concentration range of 1–60 μg/mL. Phase-solubility studies were conducted to determine the apparent stability constant (K_1:1), and inclusion complexes were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Results: The method demonstrated specificity, linearity, sensitivity, and accuracy within the tested concentration range of 1–60 μg/mL. The apparent stability constants (K_1:1), calculated from the phase-solubility plot slopes, were 2666.66 M⁻¹ for Sulfobutyl Ether β-Cyclodextrin (SBE-β-CD) and 526.3 M⁻¹ for Hydroxypropyl-β-Cyclodextrin (HP-β-CD). The solubility of RP in deionized water (0.25 mM) increased 8.6-fold to 2.15 mM with the HP-β-CD inclusion complex and 22.4-fold to 5.6 mM with the SBE-β-CD inclusion complex. The method was successfully applied to determine RP in inclusion complexes and poloxamer 407 hydrogel formulations, with no interference from formulation excipients. Conclusions: The validated RP-HPLC method is suitable for quality control analysis of RP in CD inclusion complexes and poloxamer 407 hydrogel formulations, supporting its application in the future development of these drug delivery systems. Full article

Extrusion-based bioprinting imposes stringent mechanical constraints on bioink formulations, yet the rheological parameters governing cell survival during the printing process are rarely reported in a standardized way, limiting cross-study comparison. In this work, we systematically characterized the viscoelastic properties of alginate/methylcellulose bioinks incorporating strontium-enriched hydroxyapatite (Sr-OHAp) particles and Poloxamer 188, and assessed their effect on PANC-1 cell viability in bioprinted constructs. The power law consistency index K and pseudoplasticity index n were used as quantitative descriptors of bioink behavior. Addition of Poloxamer 188 reduced K by 52.1% in particle-free inks and by 64.6% in particle-containing inks, while n remained largely unchanged (≤2% variation), indicating that particles selectively modulate consistency without compromising shear-thinning behavior. On day 1, bioprinted constructs showed lower cell viability than cell-seeded scaffolds (53.9–58.9% vs. 96.7%); however, constructs containing Sr-OHAp (B3) displayed progressive recovery, reaching 84.0% viability by day 7, compared to 72.9% for particle-free bioinks (B1). These results demonstrate that Sr-OHAp particles act as rheological sensitizers that reduce extrusion-induced shear stress while simultaneously promoting long-term cell recovery, likely through their bioactive surface chemistry. We propose that systematic reporting of K and n indices should become standard practice in bioprinting studies to enable rational bioink design and consistent knowledge accumulation across the field. Full article

An effective dermal scaffold is expected to provide a three-dimensional porous architecture that supports fibroblast adhesion, infiltration, and proliferation; evolve structurally to meet the progressive physiological needs of the entire healing process; and absorb without adverse tissue response during tissue repair. This study evaluates a fully synthetic absorbable composite electrospun matrix comprising three polymer components within a single fiber network, each contributing a distinct yet complementary function. Poloxamer 188 provides immediate wettability and conformability; PLGA undergoes progressive hydrolytic degradation over days, enlarging pore dimensions through fiber cleavage; and polydioxanone, as the slowest-degrading component, maintains the fiber network throughout this structural remodeling process. The matrix achieved instantaneous wetting and 91% maximum pore-equivalent diameter enlargement within 7 days, creating a microenvironment associated with progressive cellular accommodation. In vitro, fibroblasts adhered, remained fully viable, and exhibited Day-1 spreading on the 7-day pre-degraded matrices approaching that observed at Day 3 on fresh matrices, consistent with the evolving pore architecture facilitating initial cellular accommodation. In a splinted rat full-thickness wound model, the matrix accelerated wound-area reduction versus the control (Day 14: p < 0.001; Day 21: p < 0.01), was macroscopically undetectable by Day 14, and elicited no adverse foreign-body reaction. Quantitative collagen area fraction analysis (Masson’s trichrome) revealed significantly greater collagen content in the scaffold group at Day 7 (p < 0.05) and Day 28 (p < 0.01) relative to the control, suggesting that the composite matrix provides favorable conditions for collagen accumulation that persists into the remodeling phase. These findings demonstrate that the matrix functions as an effective dermal scaffold by providing an evolving pore architecture that supports fibroblast adhesion and accommodation, accelerating full-thickness repair throughout the healing trajectory, and undergoing safe absorption without adverse reactions, thereby highlighting its promising translational potential for clinical wound management. Full article

Objective: This study aimed to enhance wound healing by developing a delivery platform that combines camel milk-derived extracellular vesicles (CM-EVs) with a thermosensitive chitosan/Poloxamer 407 hydrogel (CM-EVs–Gel), addressing the challenges of instability, poor skin penetration, and burst release associated with EVs. Methods: CM-EVs were isolated and analyzed for size, markers, and protein content. A thermosensitive hydrogel was created and infused with CM-EVs. Its gelation, injectability, and release kinetics (using the Higuchi model) were tested. Safety was evaluated through ocular irritation and 28-day skin toxicity in rabbits. Wound healing effectiveness was tested in rats with full-thickness wounds, comparing CM-EVs–Gel, a blank hydrogel, and untreated controls. Results: CM-EVs had an average size of 108.5 nm and expressed CD63, CD81, and Alix. The hydrogel solidified at 37 °C within 10 min and followed the Higuchi model for diffusion-controlled release (R² = 0.974), releasing 81.7% of EVs over 48 h without toxicity. In rats, CM-EVs–Gel achieved 76.31% wound closure by day 6 and 94.7% by day 15, outperforming blank hydrogel (48.77% and 82.1%) and untreated controls (43.14% and 72.3%) (p < 0.01). Histology showed improved re-epithelialization, collagen deposition, and angiogenesis. Conclusions: This study shows that integrating biogenic particle engineering with optimized hydrogel systems allows for controlled release, safety, and enhanced wound healing. Despite missing free EV controls, full rheological data, and mechanistic insights, it highlights comprehensive delivery strategies from particle design to system performance, aligning with the Special Issue’s focus. Full article

Eye diseases are common in veterinary clinical practice and are most often treated with topical ophthalmic preparations. Increasing resistance to antimicrobial agents is driving the search for safe and effective alternatives to traditional treatment methods. The aim of this study was to develop and evaluate gel-based ophthalmic formulations based on poloxamer 407 and sodium carboxymethylcellulose, containing propolis extracts and diclofenac sodium, by assessing their physical and chemical properties, antimicrobial activity, and cytotoxicity in vitro. Propolis extracts were prepared using a solvent consisting of ethanol and choline chloride, and the developed formulations were evaluated for pH, viscosity, refractive index, gelation temperature, SIRC cell viability and apoptosis, and antimicrobial activity against clinical and reference bacterial strains. The developed formulations exhibited physicochemical properties suitable for ophthalmic preparations and antimicrobial activity, particularly against Gram-positive bacteria. Most of the concentrations of the active ingredients tested were well tolerated by SIRC cells, although higher concentrations of the ethanol propolis extract caused a greater cytotoxic effect. The results obtained indicate that gelled ophthalmic formulations based on propolis extracts and diclofenac sodium are promising for the further development of topically acting ophthalmic preparations; however, their biological efficacy and safety must be confirmed. The results obtained indicate that gelled ophthalmic formulations based on propolis extracts and diclofenac sodium are promising for the further development of topical ophthalmic preparations; however, their bioavailability and safety must be confirmed by further in vivo studies. Full article

Intratympanic (IT) injection of corticosteroids is a standard clinical treatment for sensorineural hearing loss; however, achieving both biocompatibility and efficient cochlea drug delivery remains a significant challenge. Herein, we engineered a novel drug nanocrystal (NS)-loaded thermo-reversible hydrogel (NS-TG) system of dexamethasone-21-palmitate (DEX-P), a lipophilic prodrug of dexamethasone (DEX), for improved IT delivery. NSs with a mean diameter of 835.0 nm were fabricated using a dual centrifugation process with polyvinyl alcohol as the stabilizer. The NS-TG system, comprising NSs in a 19% (w/v) Poloxamer 407 hydrogel, exhibited rapid gelation (2–3 min) and a 31-fold increase in drug solubility (1.57 ± 0.02 mg/mL) compared to NS alone, through micellar solubilization. In vitro cytotoxicity assays in HEI-OC1 cells revealed that NS-TG is highly biocompatible, maintaining cell viability, whereas the commercial lipid emulsion (Lipothason^®) induced significant cytotoxicity. In vivo pharmacokinetic evaluation in mice revealed that IT NS-TG provided superior cochlear drug absorption compared to DEX-SP solutions and DEX-P NS, despite showing lower absorption than the lipid emulsion. These findings suggest that the DEX-P NS-TG system, pending further investigation, could serve as a promising platform for cochlear steroidal delivery, offering an optimal balance between delivery efficiency and local safety for treating inner ear diseases. Full article

Oral ulcerations are complex pathological lesions with multifactorial etiology and diverse clinical manifestations. Current treatment options are mostly symptomatic with a different adverse effect. Therefore, this study aimed to develop a mucoadhesive oral gel containing Potentilla erecta L. ethanol extract (PEOG) and evaluate its healing effects in a rat model of oral ulceration. Dried rhizomes of Potentilla erecta were extracted with 70% ethanol using ultrasonic extraction, followed by low-pressure evaporation. The extract was incorporated into a gel base composed of poloxamer 407 and carbomer 934. Rheological characterization was performed to assess the viscoelastic and flow properties of the formulation. Therapeutic efficacy was evaluated through macroscopic assessment of ulcer healing, histopathological analysis, and determination of systemic oxidative stress biomarkers. Animals were assigned to three groups: untreated control, gel base (GB), and PEOG-treated. Rats were sacrificed on days 0, 3, 6, and 10 for blood and tissue sampling. PEOG treatment significantly accelerated ulcer healing, resulting in a marked reduction in ulcer size compared with controls. Histopathological findings indicated enhanced collagen deposition, while biochemical analyses suggested attenuation of oxidative stress. These results demonstrate that PEOG possesses considerable ulcer-healing potential and may represent a promising mucoadhesive formulation for the treatment of oral ulcerations. Full article

Andrographolide-loaded microparticles with an aqueous-based carrier system were developed with the aim of pulmonary drug delivery. Five formulations of andrographolide (0.6–5.8% w/w) loaded on mixed-polymer carriers containing chitosan (CHS), hydroxyethyl cellulose (HEC), Poloxamer 188, and PEG 20,000, with various ratios were produced under various spray-drying parameters: solution viscosity (5–20 cP), atomization air pressure (0.8–1.5 bar) and solution feed rate (3–6 mL/min). The physiochemical properties of the microparticles were strongly affected by carrier composition and atomization air pressure. The optimal formulation: andrographolide 0.6% w/w, CHS 62.2% w/w, HEC 15.5% w/w and Poloxamer 188 21.7% w/w, spray dried using solution viscosity 15 cP, atomization air pressure 1.1 bar and feed rate 3 mL/min, was selected according to its particle sizes (3–5 µm) with rough morphology, encapsulation efficiency (54.47%) and release behaviors (22.31%/h and 89.23% within 4 h). Good physical, chemical, and thermal stabilities under room storage condition (28 ± 2 °C, 50% relative humidity) were also proven. Importantly, it demonstrated potent antiviral activity against Influenza A/H1N1, achieving a 3.3-log₁₀ reduction in viral titer with 99.95% inhibition. Overall, this aqueous-based carrier approach and spray-drying technique offer a stable and effective inhalable formulation for localized treatment of influenza infections. Full article

Propolis is a widely studied natural raw material, the composition of which varies depending on the plant origin, harvest season, geographical area, climate and bee species. This large variety of chemical composition limits the use of propolis extracts in the pharmaceutical industry, which makes it difficult to ensure standardization of the raw material. One of the challenges that limit the modeling of oral pharmaceutical forms with propolis extract is the limited solubility and bioavailability of active compounds. Solid dispersion technology is commonly used in the production of oral capsules. The aim of this study is to evaluate the influence of different materials (HPMC, poloxamer and β-cyclodextrin) on the dissolution kinetics of phenolic compounds of propolis dry extract contained in capsules and their antioxidant activity in vitro. Analysis of the selected formulations showed that the major phenolic compounds detected in the propolis extract were also present in the dissolution medium samples. The auxiliary polymeric materials selected for the capsules formed a prerequisite for the dissolution kinetics profile. The addition of poloxamer and cyclodextrin increased the solubility and dissolution kinetics of hydrophobic propolis compounds in the test media. The addition of HPMC prolonged the dissolution kinetics of propolis active compounds. The antioxidant activity of the tested samples depends on the concentration of active compounds in the receptor medium by both the ABTS and DPPH methods. Full article

Dissolving microneedles (DMN) could be considered as a minimally invasive alternative for transdermal delivery of naltrexone hydrochloride (NTX). In the present study, DMN patches with smart design were developed via a two-step micromoulding technique. The systems were composed of drug-free polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) blend microneedle tips, combined with a drug-loaded backing layer based on PVP and Poloxamer 407. The influence of polymer concentration in DMN tips and backing-layer composition on morphology, mechanical properties, drug release and permeation was evaluated. Mechanical studies revealed that intermediate polymer concentration (formulation MN-20%/2:1) provided superior structural integrity (13.57 ± 1.43% height reduction after compression) and efficient penetration up to the fourth Parafilm^® layer. Incorporation of NTX into the backing layer allowed for high drug loading, while a 2:1 PVP:P407 ratio provided higher toughness (1806 g/mm) as well as thermoresponsive and controlled drug release. In vitro permeation studies demonstrated significantly enhanced NTX delivery from DMN systems compared to simple matrix patches—an almost 4-fold increase in flux with 56% permeation of NTX up to 8 h. These findings highlight the importance of polymer composition in DMN design and demonstrate the potential of the developed systems as an effective platform for transdermal delivery of NTX. Full article

Background/Objectives: Gliclazide’s limited water solubility restricts its absorption across the gastrointestinal tract and compromises its therapeutic performance. This study developed a thermoresponsive solid dispersion based on the inverted thermoresponsive behavior of poloxamer 188 in propylene glycol. Methods: A solubility study was conducted to select components for the thermoresponsive solid dispersion. An I-optimal mixture design was used to optimize the concentrations of the thermoresponsive solid dispersion components (poloxamer 188, propylene glycol, and labrasol). FTIR and XRD were used to investigate the mechanism underlying the inverted thermoresponsive behavior. Finally, the influence of the thermoresponsive solid dispersion on gliclazide dissolution was evaluated through in vitro dissolution testing. Results: Surfactant screening identified labrasol as the optimal surfactant owing to a superior increase in gliclazide solubility compared to propylene glycol alone (2.29-fold). The optimized thermoresponsive solid dispersion (poloxamer 188, propylene glycol, and labrasol at 13.89, 21.43, and 64.68% w/w, respectively) achieved a drug solubility of 10.68 mg/g and a phase transition temperature of 36 °C. XRD and FTIR confirmed that hydrogen bonding is responsible for the system’s conversion between the solid and liquid states. Compared with raw gliclazide, the optimized formulation demonstrated an 8.4-fold increase in the initial dissolution rate and significantly improved dissolution efficiency from 21.77 ± 4.74% to 74.85 ± 2.33%. Conclusions: The present thermoresponsive solid dispersion provides a green alternative to conventional solid dispersion techniques. It avoids reliance on organic solvents, processing that demands high energy input, and additional post-processing operations. Full article

Trimethyl chitosan (TMC)-coated alginate/dextran sulfate (ADS) nanoparticles were developed as mucoadhesive nanocarriers for oral insulin delivery using a Quality-by-Design strategy. In a first screening step, a two-level factorial design was applied to evaluate the influence of ADS concentration, TMC concentration, insulin concentration, and poloxamer^® concentration on particle size and encapsulation efficiency. The screening design identified the ADS-TMC pair as the main formulation parameter for particle size, while TMC and poloxamer^® were the most influential factors for encapsulation efficiency. In a second step, formulation optimization was performed using a three-factor, three-level Box–Behnken design in which ADS concentration, TMC concentration, and the degree of quaternization (DQ) of TMC were investigated as critical material attributes. Particle size, zeta potential, and in vitro mucoadhesion were selected as critical quality attributes. Across the Box–Behnken design, the experimental formulations showed particle sizes ranging from 316 to 1340 nm, zeta potentials between +17 and +39 mV, and mucin-binding values from 7 to 87%. Numerical optimization by Design-Expert^® desirability analysis identified an optimal formulation composed of 0.096% (w/v) ADS and 0.700% (w/v) TMC with 60% DQ. The model predicted a particle size of 316.24 nm, a zeta potential of +38.43 mV, and an in vitro mucoadhesion of 87.14%. Experimental confirmation yielded values of 330.79 nm, +37.09 mV, and 84.61%, respectively, with prediction errors below 5% for all responses. In simulated gastric medium, partial insulin leakage was observed during the first 120 min, whereas cumulative insulin release reached 54% after 5 h in simulated intestinal medium. These results demonstrate the usefulness of a QbD framework combined with desirability-based optimization for defining robust formulation conditions for mucoadhesive TMC-coated ADS nanoparticles intended for oral insulin delivery. Full article