Gelation Temperature Research Articles

Formulation and Characterization of Intranasal Mucoadhesive Gel of Antiallergic Drug Loratadine for Improved Bioavailability

The present study aimed to formulate and characterize an intranasal mucoadhesive gel of loratadine to enhance its bioavailability. Loratadine, an antihistamine, is commonly used for the treatment of allergic conditions, but its low bioavailability due to extensive first-pass metabolism can limit its effectiveness. To address this issue, an in situ gel formulation was developed using Poloxamer 407 and Carbopol 934 as excipients. The gel's physicochemical properties, including pH, drug content, viscosity, gel strength, gelation temperature, and drug release profile, were evaluated. FT-IR analysis revealed no significant chemical interaction between the drug and excipients, confirming the stability of the formulation. The gel exhibited shear-thinning behavior and gelation temperatures suitable for nasal administration. In vitro drug release studies showed a sustained release profile, with higher Carbopol concentrations resulting in slower drug release. The mucoadhesion time increased with Carbopol 934 concentration, ensuring prolonged retention at the nasal site. Stability studies demonstrated that the formulations remained stable under standard storage conditions. The results suggest that the loratadine-loaded mucoadhesive gel has the potential to improve the bioavailability of loratadine through intranasal delivery, offering a promising alternative to conventional oral dosage forms. Keywords: Loratadine, Mucoadhesive Gel, Poloxamer 407, Carbopol 934, In Situ Gel, Bioavailability, Drug Release, Nasal Delivery, Stability, FT-IR

Thermoresponsive Gels with Rosemary Essential Oil: A Novel Topical Carrier for Antimicrobial Therapy and Drug Delivery Applications

This study investigates the development and comprehensive characterization of innovative thermoresponsive gels incorporating rosemary essential oil (RoEO) encapsulated in poly(lactic-co-glycolic acid) (PLGA) microparticles, with a focus on their potential applications in topical antimicrobial and wound healing therapies. RoEO, renowned for its robust antimicrobial, antioxidant, and wound-healing properties, was subjected to detailed chemical profiling using gas chromatography-mass spectrometry (GC–MS), which identified oxygenated monoterpenes as its dominant constituents. PLGA microparticles were synthesized through an optimized oil-in-water emulsion technique, ensuring high encapsulation efficiency and structural integrity. These microparticles were thoroughly characterized using Fourier-transform infrared (FTIR) spectroscopy to confirm functional group interactions, scanning electron microscopy (SEM) for surface morphology, X-ray diffraction (XRD) for crystalline properties, and thermal analysis for stability assessment. The synthesized microparticles displayed uniform size distribution and efficient encapsulation, demonstrating compatibility with the gel matrix. Two distinct thermoresponsive gel formulations were developed using varying ratios of Poloxamer 407 and Poloxamer 188 to achieve optimal performance. The gels were evaluated for key physicochemical properties, including pH, gelation temperature, viscosity, and rheological behavior. Both formulations exhibited thermoresponsive gelation at skin-compatible temperatures (27.6 °C and 32.9 °C), favorable pH levels (6.63 and 6.40), and shear-thinning behavior suitable for topical application. Antimicrobial efficacy was assessed against common pathogens associated with skin infections, including Staphylococcus aureus, Escherichia coli, and Candida albicans. The RoEO-PLGA-loaded gels demonstrated significant inhibitory effects, confirming their potential as effective carriers for controlled and localized drug delivery. These findings underscore the promising application of RoEO-PLGA-loaded thermoresponsive gels in addressing challenges associated with topical antimicrobial therapies and wound care, offering an innovative approach to enhancing therapeutic outcomes. By integrating the bioactive potential of RoEO with the advanced delivery capabilities of PLGA microparticles and thermoresponsive gels, this study paves the way for the development of next-generation formulations tailored to meet the specific needs of localized drug delivery in skin health management.

Gelatins derived from aronia-supplemented fish diets: Structural effect and molecular simulation.

Fish gelatin, a sustainable substitute for mammalian gelatin, frequently exhibits weaker gel strength and thermal stability, limiting its industrial uses. This study investigated an in vivo method to improve functional characteristics by supplementing Nile tilapia diets with Aronia extract. The control diet (A0) contained no Aronia extract, while the remaining four diets consisted of commercial pelleted feed enriched with 250mg/kg (A250), 500mg/kg (A500), 750mg/kg (A750), and 1000mg/kg (A1000) of Aronia extract. The gelatin samples revealed thermo-reversible behavior with increasing temperature. A250 exhibited the highest melting temperature of 29.65°C, compared to 27.43°C for A0. The gelation temperature for A250 was 17.56°C, indicating a relatively stable gelatin structure. The elastic modulus (G') was the highest in A250, suggesting an improved gel network compared to the other samples. The gelation rate constant (kgel) was highest in A250 (540.67Pa), followed by A750 (447.32Pa), A500 (393.85Pa), and A1000 (370.97Pa), compared to 391.15Pa for A0. The gel strength was improved, with A250 showing the highest value at 133.9g, followed by A750, A1000, and A500, while A0 was 102.1g. The glass transition temperatures (Tg) for A250, fish gelatin (FG), bovine gelatin (BG), and A0 were 76.72°C, 74.31°C, 70.71°C, and 73.52°C, respectively. Molecular docking studies revealed strong binding interactions between A250 and phenolic compounds, which contributed to the observed structural enhancements. These findings suggest that supplementing fish diets with Aronia extract can substantially enhance gelatin quality, offering a promising alternative to traditional gelatin sources.

Spatiotemporal evolution of heterogeneous structures in agarose gels revealed by particle tracking.

Upon decreasing the temperature, agarose solution exhibited gelation and phase separation, forming a cloudy gel consisting of agarose-rich and agarose-poor phases. Both phenomena contribute to the formation of a heterogeneous gel structure, but the primary influence of both processes on this heterogeneity remains unclear. In this study, we defined the specific gelation and phase separation temperatures of an agarose solution and examined the resulting gel structures with and without phase separation. Microscopic observation and colloid diffusion analysis revealed that phase separation leads to inhomogeneities several micrometers in size. Furthermore, we found that the distributions of colloidal diffusion coefficients and particle displacements strongly reflected the heterogeneity primarily induced by phase separation and gelation. Our findings contribute to the physicochemical understanding of the heterogeneous structures of various (bio) polymer gels associated with the phase separation of polymers.

Thermoresponsive biomaterial system of Irinotecan and Curcumin for the treatment of colorectal cancer: In-vitro and in-vivo investigations

This study aims to develop a thermoresponsive biomaterial system of irinotecan (IRT) and curcumin (CUR) nano-transferosomal gel (IRT-CUR-NTG) for targeting colorectal cancer (CRC). The IRT-CUR-NTs were statistically optimized and loaded into poloxamer-based thermosensitive gel. Transmission electron microscopy (TEM), Differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) of the IRT-CUR-NTs were performed, whereas pH, gelation time, gelation temperature, gel and mucoadhesive strength of the IRT-CUR-NTG were investigated. In-vitro release and anticancer analyses were explored using HT29 cells. Additionally, in-vivo pharmacokinetics study was investigated followed by histopathological examination and in-vivo anticancer analysis. The PS, PDI, ZP, %EE of IRT and %EE of CUR were found to be 136.15 nm, 0.143, -15.5 mV, 95.05% and 85.12%, respectively. IRT-CUR-NTs exhibited spherical shape with no chemical interactions among the constituents. Similarly, IRT-CUR-NTG was homogenous gel suitable for rectal administration. IRT-CUR-NTG manifested prolonged release profiles of IRT and CUR. Moreover, a significantly enhanced (4-fold) bioavailability and no toxicity of IRT-CUR-NTG was observed when compared with conventional gel. IRT-CUR-NTs were found to be more effective against HT29 cell lines. In-vivo antitumor analysis demonstrated significantly reduced tumor volume and tumor mass after treatment with IRT-CUT-NTG, indicating improved antitumor effect. It can be concluded that IRT-CUR-NTG is suitable biomaterial system for colorectal cancer.

Upgrading skin barrier Protection: Addition of active ingredients to a Gelatin/Tannic Acid-Based hydrogel patch for treating skin lesions related to Personal protective Equipment.

Prolonged use of Personal Protective Equipment, like surgical masks, can cause skin issues such as acne ("maskne") and rosacea flare-ups due to pressure and moisture. While dressings can protect the skin, they often reduce mask effectiveness and lack pharmaceuticals to treat common skin lesions. This study introduces an innovative dual-function gelatin/tannic acid-based hydrogel patch incorporating metronidazole (1% w/w) or salicylic acid (2% w/w) to offer both skin protection and treatment. The hydrogels were characterized for gelation temperature, burst strength, extensibility, adhesivity, and tribological properties to assess the effects of the active ingredients on their mechanical performance. In vitro release studies using Franz diffusion cells under occlusive conditions evaluated the drug release profile from the patches. Results showed that gelatin/tannic acid and gelatin/tannic acid-metronidazole hydrogels had similar gelation temperatures (41.65 ± 1.95 °C), while the salicylic acid formulation exhibited a lower gelation temperature (33.24 ± 0.40 °C). Adhesivity improved with the addition of active ingredients, increasing by about 0.5 N, and burst strength significantly increased with metronidazole (about 6 N). Both formulations demonstrated enhanced extensibility and were suitable for all skin types in tribological studies. The in vitro release studies showed an initial burst release followed by controlled release, unaffected by mask placement. These findings suggest that dual-function hydrogel patches could provide effective skin protection and improve skin health during prolonged mask use, offering a promising solution for conditions like "maskne" and rosacea.

Influence of CO2 Treatment Pressure on the Chemical Composition and Rheological Properties of Degassed Waxy Crude Oil.

With the gradual application of enhanced oil recovery by CO2 (CO2-EOR), the rheological behavior of produced fluid is altered due to CO2 dissolution and degassing. This work focuses on the composition, physical properties, gelation and yield characteristics, and viscosity-temperature properties of crude oil containing paraffinic wax after CO2 treatment. Special attention is given to the effect of the phase state of CO2. It is found that the contents of light hydrocarbons (C9-) and liquid paraffin (C9-C16) decrease by 1.24% and 0.89%, respectively, while the contents of paraffin and microcrystalline wax increase by 1.90% and 1.71%, respectively, as the treatment pressure is increased to 25 MPa from atmospheric pressure. Besides, the content of the saturates decreases by 5.31%, while that of the aromatics, resins, and asphaltenes increases by 2.83%, 1.83%, and 0.65%, respectively, due to the extraction effect of CO2 on light hydrocarbons. In terms of wax precipitation characteristics, the wax appearance temperature (WAT) and wax precipitation content (WPC) increase with increasing pressure. Particularly, when the pressure increases from 5 to 15 MPa, the WAT and WPC increase by 4 °C and 1.27%, respectively, obviously greater than the other conditions due to the phase transition of CO2. Moreover, the morphology of the wax crystals becomes tinier after supercritical CO2 (scCO2) treatment because of the increase in the polarity of the crude oil. Likewise, considering the gelation and yield characteristics, the storage modulus, gelation temperature, and yield stress increase more obviously than the other pressure change conditions as the pressure increases from 5 to 15 MPa. All of the above structural enhancements are owing to the effect of CO2 treatment, especially scCO2 treatment, on the content and morphology of the precipitated wax crystals. Last, the apparent viscosity/viscosity also increases with the treatment pressure. The viscosity increases by 1.1 to 2.0 times with the pressure increasing from 5 to 15 MPa, again obviously greater than the other pressure change conditions due to the interior structural changes of the crude oil induced by scCO2 treatment..

Characterization of Biopolymer Hydrogels Prepared with Water Exposed to Indirect Plasma Treatment.

This study aimed to evaluate the influence of indirect-plasma-treated water (IPTW) in the preparation of hydrogels. Three commonly used natural, biodegradable polymers with the ability to form gels were selected: gelatin, carrageenan, and sodium alginate. The pH, gelling temperature, texture profile, swelling degree, and color of hydrogels were evaluated, and the polymers were subjected to Fourier-transform infrared (FTIR) spectroscopy. The morphology of the hydrogels was investigated using Scanning Electron Microscopy (SEM). Additionally, the physiochemical properties of the water media, which were distilled water (DW) and IPTW, were analyzed. The results indicated that the gels prepared using IPTW were characterized by a lower pH, higher hardness and lower gelation temperature. After 48 h of swelling ratio (SR) testing, gelatin and alginate hydrogels made with IPTW were characterized by lower SR, while an inverse relationship was found in the case of SR of carrageenan gels. The FTIR analysis confirmed changes in the water binding ability. The use of IPTW also significantly affected the microstructure of the tested materials. A statistically significant change in the color of IPTW gel samples was also noted. The results showed that IPTW induces physicochemical changes in hydrogels, which can lead to the enhancement of their practical applications.

Preparation and Antibacterial Activity Evaluation of Daphnetin-Loaded Poloxamers/Polyvinylpyrrolidone Thermosensitive Hydrogels.

Antibiotic misuse and bacterial resistance are pressing issues threatening public health. Natural plant extracts with bactericidal properties offer potential alternatives to reduce or replace antibiotic use. This study aims to develop a thermosensitive hydrogel containing daphnetin (DAP-TG) using poloxamers 407 (P407), polyvinylpyrrolidone (PVP), and poloxamers 188 (P188). We systematically evaluated the gel's antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), as well as its antibacterial mechanisms. By examining the gelation temperature and time, degradation time, and in vitro release performance of DAP-TG, we produced a sustained-release DAP-TG with a rapid phase transition at (31.6 ± 0.1) °C. Its structure was characterized through Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The results indicated that the DAP thermosensitive hydrogel was formed and presented a 3D network spatial structure. The biocompatibility of DAP-TG was explored through the hemolysis test and cytotoxicity test. The results indicated that DAP-TG possessed excellent biocompatibility. The antibacterial efficacy of DAP-TG against E. coli and S. aureus was assessed using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), growth curve, and inhibition zone tests. Results showed that DAP-TG exhibited excellent antibacterial activity against both E. coli and S. aureus, with MIC values of 1.28 and 0.32 mg/mL. The antibacterial mechanism of DAP-TG was preliminarily explored through the investigation of bacterial cell content leakage, AKP leakage, membrane permeability, SEM, ROS production, and biofilm inhibition activity. DAP-TG induced irreversible damage to the cell membranes of E. coli and S. aureus, resulting in enhanced permeability, elevated ROS levels, and inhibited biofilm formation. Our study indicates that DAP-TG exhibits effective sustained-release and antibacterial properties against E. coli and S. aureus in vitro, making it a promising candidate for antibacterial applications in food and pharmaceutical products.

Glycyrrhizic Acid-Loaded Poloxamer and HPMC-Based In Situ Forming Gel of Acacia Honey for Improved Wound Dressing: Formulation Optimization and Characterization for Wound Treatment.

The present study aims to formulate a stimuli-responsive in situ hydrogel system to codeliver acacia honey and glycyrrhizic acid for topical application that will aid in absorbing wound exudates, control microbial infestation, and produce angiogenic and antioxidant effects to accelerate wound healing. Therefore, both the natural active constituents were incorporated within an in situ hydrogel composed of poloxamer and hydroxypropyl methylcellulose (HPMC), where the concentrations of the polymers were optimized using Design-Expert software considering optimum values of the dependent variables, gelation temperature (34-37 °C), gelation time (<10 min), and the viscosity (2000-3500 cPs). The optimized formulation showed improved physicochemical properties such as mucoadhesiveness, porosity, swelling, and spreadability, which makes it suitable for wound application. Additionally, the in situ hydrogel exhibited potent in vitro and ex vivo antioxidant effects, in vitro antimicrobial activities, and ex ovo angiogenic effects. Furthermore, the optimized formulation was found to be nontoxic while tested in the HaCaT cell line and acute dermal irritation and corrosion study. The findings of the in vivo wound-healing studies in experimental animal models showed complete wound closure within 15 days of treatment and accelerated development of the extracellular matrix. In addition, the antioxidant, antimicrobial, angiogenic, and wound-healing properties of acacia honey and glycyrrhizic acid coloaded in situ hydrogel were also found to be promising when compared to the standard treatments. Overall, it can be concluded that the optimized stimuli-responsive in situ hydrogel containing two natural compounds could be an alternative to existing topical formulations for acute wounds.

In Situ Thermosensitive Mucoadhesive Nasal Gel Containing Sumatriptan: In Vitro and Ex Vivo Evaluations.

The aim of this study was to develop a thermosensitive mucoadhesive (MA) in situ nasal gel for sumatriptan. A 3D response surface methodology (Design of Expert version 11) was employed to formulate nine different formulations. The Pluronic F-127 concentration (X1) and chitosan concentration (X2) were selected as independent factors. The formulas were studied in terms of pH, clarity, drug content, gelation temperature, gelation time, gel strength, MA strength, viscosity, % release after 5 h, and release kinetics. The optimized formulas were studied for % permeated after 5 h and stability in addition to previous tests. The study of the stability of the optimized formula was performed under accelerated conditions (40 ± 2 °C, 75 ± 5% RH) for 3 months. The outcomes of the optimized formula were a clear gel with a gelation temperature of 33 °C and a reasonable gelation time of less than one minute, and the release and permeation during 5 h were 40% and 50%, respectively. The formulated gel decreased the mucociliary clearance (MCC) and thus increased the retention time in the nasal cavity, resulting in enhancing SMT absorption, which could improve the drug efficacy.

Mechanisms of Low Temperature Thickening of Different Materials for Deepwater Water-Based Drilling Fluids.

During deepwater drilling, the low mudline temperatures and narrow safe density window pose serious challenges to the safe and efficient performance of deepwater water-based drilling fluids. Low temperatures can lead to physical and chemical changes in the components of water-based drilling fluids and the behavior of low temperature gelation. As a coarse dispersion system, water-based drilling fluid has a complex composition of dispersed phase and dispersing medium. Further clarification of low temperature gelation would be helpful in developing technical approaches to enhance the flat rheology performance of deepwater water-based drilling fluids. In this paper, different components are separated in order to comprehensively analyze the gelation behavior of different materials in water-based drilling fluids at low temperatures. In the first place, the rheological and hydrodynamic radius alterations of inorganic salts, bentonite, and additives in aqueous solutions were examined at low temperatures. The effects of inorganic salts, bentonite, and additives on the purified water system were investigated at low (4 °C)-normal (25 °C)-high (75 °C) temperatures. The low temperature gelation of different materials in pure water systems are fully clarified. The mud containing 4% bentonite with weak low temperature gelation commonly used in deepwater water-based drilling fluids was selected as the basic test system. Inorganic salts, additives, and solid-phase materials were added to the mud containing 4% bentonite. The effects of the interactions between different materials and bentonite particles on the low temperature gelation behavior of mud were analyzed. The higher the bentonite dosage, the stronger the low temperature gelation behavior of mud. The higher the addition of inorganic salts, the more serious the low temperature gelation behavior of mud. Inorganic salts should be avoided as much as possible to add too much. The low temperature gelation behavior of mud with low-viscosity additives is weak. However, the viscosity of mud with high-viscosity additives has a small change in viscosity with increasing temperature. The low temperature gelation of mud with the addition of solid-phase particulate materials with reactive groups on the surface is strong, and the low temperature gelation with the addition of inert particles is weak. This paper elucidates the low temperature gelation mechanism of bentonite, inorganic salts, additives, and solid-phase materials in deepwater water-based drilling fluids. The conclusion can also be used to guide the construction of a drilling fluid system, which is of great significance for the research and development of deepwater water-based drilling fluid additives and the safe and efficient performance of deepwater drilling fluids.

Development of Lacosamide-loaded In-Situ Gels through Experimental Design for Evaluation of Ocular Irritation In Vitro and In Vivo.

Lacosamide (LCM) selectively increases the slow inactivation of voltage-gated sodium channels (VGSCs) and is a N-methyl D-aspartate acid (NMDA) receptor glycine site antagonist. Therefore, it can be used in dryness-related hyperexcitability of corneal cold receptor nerve terminals. Ocular in-situ gels remain in liquid form until they reach the target site, where they undergo a sol-gel transformation in response to specific stimuli. They can show mucoadhesive properties related to the polymer used and increase the residence time of the drug in the mucosa. In the presented study, ocular in-situ gel formulation of LCM, which has potential for use in ocular diseases and consists of hyaluronic acid and poloxamer 407 as polymers, was developed using cold method. The effect of formulation components on target product properties (pH, gelation temperature and viscosity) was evaluated by design of experiments (DoE) design. The optimized LCM-loaded in-situ gel had a pH value of 6.90 ± 0.01, showed pseudo-plastic flow with a viscosity of 562 ± 58 cP at 25°C, gelled at 33 ± 0.47°C, and released drugs via the Peppas-Sahlin mechanism. Ocular safety was confirmed via in vitro tests using two different cell lines (L929 and Arpe-19), along with in vivo Draize tests, histological examinations, and Hen's Egg Chario-Allontioc-Membrane (HET-CAM) analysis. In vitro studies confirmed the optimized LCM-loaded in-situ gel's suitability for ocular use, demonstrating long-acting effects through controlled release. In addition, ocular irritation and histological studies have supported that it will not show any toxic effect on the eye tissue.

Development of in vitro and in vivo evaluation of mucoadhesive in-situ gel for intranasal delivery of vinpocetine

Alzheimer’s disease (AD), which is marked by gradual neuronal decline and subsequent loss of cognitive functions and memory, poses significant treatment challenges. The present study involved the development, in vitro, and in vivo evaluation of a novel intranasal mucoadhesive in-situ gel of vinpocetine (VIN) with the aim to target the brain. An innovative gel formulation composed of poloxamer 407, HPMC E15 LV, and citric acid as a solubilizer was developed by 23 Factorial Design. The developed optimal formulation exhibited favorable rheological properties as it displayed ideal gelation time (31.6 ± 1.52 sec), optimum gelling temperature (32 ± 1.0 °C), enhanced mucoadhesive strength (6622 ± 2.64 dynes/cm2), prolonged adhesion (7.22 ± 0.57 hrs) compared with the baseline formulation (F18), and improved drug release in 12 hrs (39.59 ± 1.6%). In vivo, pharmacokinetics revealed a significant increase in Cmax (∼2-fold) and AUC0-t (∼2-fold) in the brain with the in-situ intranasal gel compared to the oral route. In the rat model of AD, in-situ intranasal gel demonstrated significantly greater efficacy (p < 0.001) than oral administration in alleviating AD symptoms as evidenced by behavioral and histological studies. Thus, VIN in-situ gel can be safe and noninvasive for nose-to-brain drug delivery.

Fabrication and evaluation of lidocaine-loaded thermoresponsive organogels for enhanced pain management in dry socket wounds

The study focuses on developing mucoadhesive thermoresponsive organogels for sustained lidocaine (LD) release, aiming to improve pain management in dry socket wounds. Using a three-level, two-factor full factorial design with a center point, lidocaine-loaded thermoresponsive organogels (LTG) formulations were created with varying concentrations of polyethylene glycol 400 (PEG400) and tween80 (T80), alongside key components like poloxamer407 (P407), PEG4000, and Sacha Inchi oil. Ten formulations were prepared and evaluated for particle size, polydispersity index, swelling index, viscosity, gelation temperature, and gelation time. Results revealed that PEG400 and T80 had significant quadratic or interaction effects on the LTG properties, with P407 and PEG4000 driving the thermoresponsive behavior. PEG400 and T80 notably improved mucoadhesion and increased viscosity. Higher concentrations of T80 enhanced heat tolerance, reduced swelling, and increased formulation stability, allowing autoclave sterilization, which ensures safe use on open wounds. The optimized LTP formulations provided sustained LD release for 72 h, following the Higuchi model. Biodegradability, measured by weight remaining, inversely correlated with viscosity and drug release. In vivo tests using mouse tail flick and hot plate models confirmed that LTG with high PEG400 and T80 concentrations exhibited superior anesthetic effects compared to LD hydrogel and LD solutions. These results suggest that the optimized LTG formulations offer significant potential for managing pain in dry socket wounds, combining ease of application, sustained release, and effective local anesthesia.

Optimizing Ocular Therapy: A Synergistic Approach with Thermosensitive Poloxamer 407 and Chitosan in In Situ Gel Formulation

Thermosensitive in situ gels in ocular drug delivery present a breakthrough in optimizing therapeutic outcomes. Responsive to physiological temperature, these gels undergo a transition from liquid to gel upon contact with the ocular surface. This unique property enhances drug bioavailability and extends retention time, overcoming challenges posed by rapid tear turnover. The gel viscosity promotes sustained drug release, minimizing the need for frequent administrations. In this study, a thermosensitive polymer base of poloxamer 407 was combined with chitosan to produce an in situ levofloxacin gel. Characterisation was carried out to see the effect of both polymers on the physicochemical properties of the resulting gel such as appearance, pH, gelation time and temperature, viscosity, and drug release. Attenuated Total Reflector (ATR) spectroscopy was employed to investigate the molecular interactions. Subsequently, the antibacterial activity was comparatively evaluated with a market product. This study aimed to develop Levofloxacin (LFX) in situ gel using poloxamer 407 (PLX407) and chitosan (CHT). Both polymers significantly influenced gelation characteristics, aligning with physiological eye mucosa temperature (34°C). PLX407's thermosensitivity played a vital role in gelation, decreasing solubility with temperature rise. Synergistic involvement of PLX407 and CHT resulted in lower gelation temperatures and times with higher PLX407 concentrations. At low CHT concentrations (&lt;0.4%), increased concentration decreased gelation time. CHT's ability to accelerate dehydration and form crosslinks enhanced gel strength. The drug release profile followed a first-order model, suggesting controlled release, but the Korsmeyer-Peppas model indicated a super case II mechanism. In practice, shear forces and dilution lead to dissolution and erosion, but the dialysis membrane may restrict observation. This highlights the importance of practical relevance in experimental design.

Thermosensitive in-situ gel of Nifedipine: A strategy to offset cognition impairment in Alzheimer's disease

Increased intracellular Ca2+ accumulation plays a pivotal role in the development and progression of Alzheimer's disease (AD). Thus, utilization of calcium channel blockers presents an elite option to combat AD-associated cognition impairment. The present work investigated the neuroprotective potential of nifedipine, a L-type calcium channel blocker (LTCC) by preparing a nanostructured lipid carrier-based intranasal in-situ gelling system (NF-NLC gel). The prepared NF-NLCs were optimized using 32 Full factorial design wherein the ratio of solid: liquid lipid was considered as an independent variable. The prepared NF-NLCs had optimal particle size of ∼94.86±14.04 nm, with PDI of ∼0.189±0.02, ZP of ∼−12.1 ± 10.05 mV, and % entrapment efficiency of ∼90.5±15.21%. Transmission electron microscopy displayed spherical morphology of NF-NLCs. Further, NF-NLCs were loaded into a thermosensitive gel matrix comprised of HPMC K4M (0.3%) and Poloxamer 407 (15%). The prepared NF-NLC gel exhibited optimal gelation time, temperature, and pseudo-thixotropic behavior. Moreover, the gelling system showed sustained release (∼24h) and enhanced permeation across the nasal mucosa. The in-vivo studies in the AlCl3 induced AD model revealed substantial improvement in cognitive ability along with reduced oxidative damage. Overall, the developed NF-NLC gel presents a viable strategy to combat cognition impairment in AD.

Preparation and Evaluation of Poloxamer/Carbopol In-Situ Gel Loaded with Quercetin: In-Vitro Drug Release and Cell Viability Study.

Periodontitis is a severe chronic inflammatory disease, whose traditional systemic antimicrobial therapy faces great limitations. In-situ gels provide an effective solution as an emerging local drug delivery system. In this study, the novel thermosensitive poloxamer/carbopol in-situ gels loaded with 20μmol/L quercetin for the treatment of periodontitis were prepared by cold method. Thirteen batches of in-situ gels based on two independent factors (X1: poloxamer 407 and X2: carbopol 934P) were designed and optimized by the statistical method of central composite design (CCD). The transparency, pH, injectability, viscosity, gelation temperature, gelation time, elasticity modulus, degradation rate and in-vitro drug release studies of the batches were evaluated, and the percentage of drug release in the first hour, the time required for 90% drug release, gelation temperature, and gelation time were selected as dependent variables. These two independent factors significantly affected the four dependent variables (p < 0.05). The optimization result displayed that the optimized concentration of poloxamer 407 was 20.84% (w/v), and carbopol 934P was 0.5% (w/v). The optimized formulation showed a clear appearance (++), acceptable injectability (Pass), viscosity(151,798mPas), gelation temperature (36°C), gelation time (213s), preferable cell viability and cell proliferation, conformed to first-order release kinetics, and had a significant antibacterial effect. The article demonstrates the great potential of the quercetin in-situ gel as an effective treatment for periodontitis.

Optimizing nutraceutical-loaded trehalosomes in-situ gel for diabetic cataract management: Comprehensive in vitro and in vivo evaluations

This study aimed to develop Baicalin-loaded trehalosomes in situ gel (BA-THs-ISG) for the treatment of cataract, a degenerative eye condition that requires innovative approaches to enhance visual acuity and quality of life. A 33 D-optimal design was implemented for the preparation and statistical optimization of BA-THs. Various in-vitro studies were conducted to evaluate the features of the optimized formula, which was subsequently loaded into an optimum ISG to sustain the release pattern. To assess the therapeutic efficacy of BA-THs-ISG, an in-vivo study was conducted using a streptozotocin (STZ) induced diabetic cataract model. The results demonstrated that the optimized formula of desirability function of 0.878 had a particle size (PS) of 237.9 ± 2.87 nm, a polydispersity index (PDI) of 0.27 ± 0.03, a zeta potential (ZP) of −27.31 ± 1.27 mV, an entrapment efficiency (EE%) of 74.32 ± 1.08 % and sustained drug release over 6 h. After being loaded into ISG, BA-THs-ISG exhibited a gelation temperature of 35.00 ± 0.30 °C and a gelation time of 49 ± 2.63 s, meeting the intended criteria. Moreover, it effectively maintained drug release for a duration of 12 h. Compared to the BA solution in the in-vivo studies, BA-THs-ISG significantly reduced malondialdehyde content and enhanced superoxide dismutase and glutathione peroxidase activities without any irritation potential. Therefore, BA-THs-ISG is inferred to be a highly effective option for improving cataract symptoms.

Effects of intravaginal curcumin gels combined with electroporation on vulvovaginal candidiasis

ObjectiveTo provide a curcumin-based vaginal gel combined with electroporation for the treatment of vulvovaginal candidiasis (VVC) caused by Candida albicans. MethodsTemperature-sensitive in situ gels (ISG) were prepared using poloxamers 407 and 188 as matrices. The mass ratio of poloxamer 407 and poloxamer 188 was 7:1 with a gelation temperature of approximately 29°C and gelation time of 2.5 min. ResultsElectroporation increased the transmucosal permeability of the model drug, doxorubicin and improved the antifungal effects of curcumin. In vitro antifungal experiments showed that the number of fungal colonies in curcumin ISG combined with electroporation was lower than that in pure curcumin ISG. In vivo pharmacodynamic experiments showed that, compared to the model group, curcumin ISG with electroporation inhibited the growth of C. albicans, alleviated vaginal mucosal edema, and reduced the inflammatory response. ConclusionCurcumin ISG combined with electroporation has substantial potential for the efficient clinical treatment of VVC.