Insight into the mechanism of the aggregation behavior of wheat protein modulated by l-lysine under microwave irradiation.

This study explored the mechanism of l-lysine intervention in wheat gluten protein (WG) gel formation under a microwave (MW) field. The results showed that the MW treatment had higher ζ-potential values at the same heating rate. After adding l-lysine, the solution conductivity and dielectric loss were significantly increased. Moreover, the WG gel strength enhanced 4.40% under the MW treatment. The Fourier spectra showed that the α-helix content was decreased 13.78% with the addition of lysine. The ultraviolet absorption spectra and fluorescence spectra indicated that MW irradiation impacted the interactions between WG molecules more effectively than the water bath heating, promoting the denaturation and unfolding of the protein structure. In addition, scanning electron microscopy analysis showed that the incorporation of lysine promoted an ordered network structure formation of the protein, which enhanced the gel properties. This indicated that the zwitterion of l-lysine played a regulatory role in the aggregation of proteins in the MW field.

Concentrated surfactant gel dressing for effective wound healing in pediatric patients: a case series.

BACKGROUND: CSG dressing is water-soluble and helps to hydrate the wound, control exudate, and provide gentle debridement by virtue of a high concentration of surfactant micelles. The primary objective of this retrospective case series is to report on the feasibility of CSG use in pediatric wounds and its mechanism of action. The secondary aim was to measure pain during application and removal of CSG. METHODS: Eight pediatric patients ranging in age from newborn to a few months old with wounds requiring medical intervention were treated with CSG. The CSG dressing was applied twice daily at initiation of treatment in some patients, but mostly once daily. NIPS was utilized for pain measurements. RESULTS: Near-complete healing of wounds was observed by the end of treatment duration, which was only a few days. The calm temperament of these patients during dressing changes and objective NIPS suggested minimal to no pain. None of the patients experienced any adverse events related to the use of this dressing. CONCLUSION: The CSG dressing could be the dressing of choice in this population to enhance debridement and maintain moist healing and support granulation, either proactively or if other treatments fail.

Efficacy of autologous platelet-rich plasma gel in patients with hard-to-heal diabetic foot ulcers: a multicentre study in Japan.

OBJECTIVE: To evaluate the healing outcome of a platelet-rich plasma (PRP) gel prepared using TKKT01 (a wound care device to prepare the PRP gel) in patients with hard-to-heal diabetic foot ulcers (DFUs) and who showed an inadequate response to ≥4 weeks of standard of care (SoC). METHOD: This open-label, single-arm, multicentre study was conducted in 15 centres in Japan. Eligible patients received PRP gel treatment twice a week for eight weeks, followed by a final evaluation after the completion of week 8 (day 57). The primary endpoint was the percentage of patients who achieved ≥50% reduction in wound radius at the final evaluation (achievement criterion, ≥60% of patients). Secondary endpoints included: wound area and volume reduction rates; time to possible wound closure by secondary intention; time to possible wound closure using a relatively simple procedure (e.g., skin graft and suture); and safety at the final evaluation. RESULTS: A total of 54 patients were included in the full analysis set, with 47 patients included in the per protocol set; the primary endpoint was met in 38/47 (80.9%) (95% confidence interval: 66.7-90.9%) patients who achieved ≥50% wound radius reduction at the final evaluation. High rates of wound area (72.8%) and volume (92.7%) reduction were observed at the final evaluation. The median time to possible wound closure by secondary intention and by use of a relatively simple procedure was 57 and 43 days, respectively. Complete wound closure at the final evaluation was achieved in 27 (57.4%) patients. No safety concerns were raised. CONCLUSION: In this study, the efficacy and safety of PRP gel treatment with TKKT01 in patients with hard-to-heal DFUs in Japan were confirmed by our findings. DECLARATION OF INTEREST: This study was funded by Rohto Pharmaceutical Co., Ltd., Japan. NO has been paid a consulting fee by Rohto Pharmaceutical Co., Ltd. KH is the Chief Medical Officer of Rohto Pharmaceutical. Co., Ltd. The other authors have no conflict of interest to declare.

Investigating the effects of oil type, emulsifier type, and emulsion particle size on textured fibril soy protein emulsion-filled gels and soybean protein isolate emulsion-filled gels.

The effects of oil type, emulsifier type, and emulsion particle size on the texture, gel strength, and rheological properties of SPI emulsion-filled gel (SPI-FG) and TFSP emulsion-filled gel (TFSP-FG) were investigated. Using soybean protein isolate or sodium caseinate as emulsifiers, emulsions with cocoa butter replacer (CBR), palm oil (PO), virgin coconut oil (VCO), and canola oil (CO) as oil phases were prepared. These emulsions were filled into SPI and TFSP gel substrates to prepare emulsion-filled gels. Results that the hardness and gel strength of both gels increased with increasing emulsion content when CBR was used as the emulsion oil phase. However, when the other three liquid oils were used as the oil phase, the hardness and gel strength of TFSP-FG decreased with the increasing of emulsion content, but those of SPI-FG increased when SPI was used as emulsifier. Additionally, the hardness and gel strength of both TFSP-FG and SPI-FG increased with the decreasing of mean particle size of emulsions. Rheological measurements were consistent with textural measurements and found that compared with SC, TFSP-FG, and SPI-FG showed higher G' values when SPI was used as emulsifier. Confocal laser scanning microscopy (CLSM) observation showed that the distribution and stability of emulsion droplets in TFSP-FG and SPI-FG were influenced by the oil type, emulsifier type and emulsion particle size. SPI-stabilized emulsion behaved as active fillers in SPI-FG reinforcing the gel matrix; however, the gel matrix of TFSP-FG still had many void pores when SPI-stabilized emulsion was involved. In conclusion, compared to SPI-FG, the emulsion filler effect that could reinforce gel networks became weaker in TFSP-FG.

Efficacy of soothing cream gel in the range of motion and chronic pain at the shoulder and elbow: protocol of a double-blinded, randomised, placebo-controlled trial.

INTRODUCTION: Upper limb problems have a significant impact on the global population leading to pain and restricted joint mobility, ultimately impacting their quality of life. Traditional treatments, such as non-steroidal anti-inflammatory drugs and corticosteroids, often come with undesirable side effects, prompting patients to seek alternative therapies. In this trial, we hypothesise that soothing cream gel (SCG) will improve range of motion and chronic pain in the shoulder and elbow. The objective of this trial is to evaluate the efficacy of SCG in improving the range of motion and chronic pain in the shoulder and elbow. METHODS AND ANALYSIS: A double-blinded, randomised, placebo-controlled trial is conducted to compare the effects of SCG and placebo gel. SCG contains Vitis vinifera essence, Melaleuca viridiflora essential oil, etc, and is manufactured according to Good Manufacturing Practice standards. The placebo gel will be processed with similar appearance, texture and scent but will lack active ingredients. 70 participants with upper limb problems will be recruited from four study sites, including clinical centres and a sport department at the Chinese University of Hong Kong (CUHK). Participants will be randomly assigned to either treatment group or placebo group for 2 weeks. Primary outcome will be the range of motion in the upper limb, assessed by a goniometer, to measure active flexion and abduction for the shoulder, and active flexion and extension for the elbow. The primary efficacy analyses will be based on the full analysis set following the intention-to-treat principle. ETHICS AND DISSEMINATION: The trial has obtained approval from the joint CUHK-New Territories East Cluster (CRE-2023.142), and the patient enrolment commenced in July 2023. Written informed consent will be obtained from all participants prior to participation. Study results will be disseminated through publication in peer-reviewed journals and presentations at conference. TRIAL REGISTRATION NUMBER: NCT05799391.

Preparation of Microsponge Drug Delivery System (MSDDS) Followed by a Scale-Up Approach.

In 1987, Won invented the solid-phase porous microsphere (MS), which stores bioactive compounds in many interconnected voids. Spherical particles (5-300 µm), MS, may form clusters of smaller spheres, resulting in many benefits. The current investigation focussed on gel-encased formulation, which can be suitable for dermal usage. First, quasi-emulsion (w/o/w) solvent evaporation was used to prepare 5-fluorouracil (5 FU) MS particles. The final product was characterized (SEM shows porous structure, FTIR and DSC showed drug compatibility with excipients, and gel formulation is shear-thinning) and further scaled up using the 8-fold method. Furthermore, CCD (Central Composite Design) was implemented to obtain the optimized results. After optimizing the conditions, including the polymer (600 mg, ethyl cellulose (EC), eudragit RS 100 (ERS)), stirring speed (1197 rpm), and surfactant concentration (2% w/v), we achieved the following results: optimal yield (63%), mean particle size (152 µm), drug entrapment efficiency (76%), and cumulative drug release (74.24% within 8 h). These findings are promising for industrial applications and align with the objectives outlined in UN Sustainable Development Goals 3, 9, and 17, as well as the goals of the G20 initiative.

Alternatives to Conventional Topical Dosage Forms for Targeted Skin Penetration of Diclofenac Sodium.

Skin penetration of an active pharmaceutical ingredient is key to developing topical drugs. This penetration can be adjusted for greater efficacy and/or safety through the selection of dosage form. Two emerging dosage forms, cream-gel and gel-in-oil emulsion, were tested for their ability to deliver diclofenac into the skin, with the target of maximising skin retention while limiting systemic exposure. Prototypes with varying amounts of solvents and emollients were formulated and evaluated by in vitro penetration testing on human skin. Cream-gel formulas showed better skin penetration than the emulgel benchmark drug even without added solvent, while gel-in-oil emulsions resulted in reduced diffusion of the active into the receptor fluid. Adding propylene glycol and diethylene glycol monoethyl ether as penetration enhancers resulted in different diclofenac penetration profiles depending on the dosage form and whether they were added to the disperse or continuous phase. Rheological characterisation of the prototypes revealed similar profiles of cream-gel and emulgel benchmark, whereas gel-in-oil emulsion demonstrated flow characteristics suitable for massaging product into the skin. This study underlined the potential of cream-gel and gel-in-oil emulsions for adjusting active penetration into the skin, broadening the range of choices available to topical formulation scientists.

Controlling Drug Partitioning in Individual Protein Condensates through Laser-Induced Microscale Phase Transitions.

Gelation of protein condensates formed by liquid-liquid phase separation occurs in a wide range of biological contexts, from the assembly of biomaterials to the formation of fibrillar aggregates, and is therefore of interest for biomedical applications. Soluble-to-gel (sol-gel) transitions are controlled through macroscopic processes such as changes in temperature or buffer composition, resulting in bulk conversion of liquid droplets into microgels within minutes to hours. Using microscopy and mass spectrometry, we show that condensates of an engineered mini-spidroin (NT2repCTYF) undergo a spontaneous sol-gel transition resulting in the loss of exchange of proteins between the soluble and the condensed phase. This feature enables us to specifically trap a silk-domain-tagged target protein in the spidroin microgels. Surprisingly, laser pulses trigger near-instant gelation. By loading the condensates with fluorescent dyes or drugs, we can control the wavelength at which gelation is triggered. Fluorescence microscopy reveals that laser-induced gelation significantly further increases the partitioning of the fluorescent molecules into the condensates. In summary, our findings demonstrate direct control of phase transitions in individual condensates, opening new avenues for functional and structural characterization.

A co-assembly process for high strength and injectable dual network gels with sustained doxorubicin release performance.

Adopting a non-covalent co-assembly strategy shows great potential in loading drugs efficiently and safely in drug delivery systems. However, finding an efficient method for developing high strength gels with thixotropic characteristics is still challenging. In this work, by hybridizing the low molecular weight gelator fluorenylmethyloxycarbonyl-phenylalanine (Fmoc-F) (first single network, 1st SN) and alginate (second single network, 2nd SN) into a dual network (DN) gel, gels with high strength as well as thixotropy were prepared efficiently. The DN gels showed high strength (103 Pa in SN gels and 105 Pa in DN gels) and thixotropic characteristics (yield strain <25%; recovery ratio >85% within 100 seconds). The application performance was verified by loading doxorubicin (DOX), showing better encapsulation capacity (77.06% in 1st SN, 59.11% in 2nd SN and 96.71% in DN) and sustained release performance (lasting one week under physiological conditions) than single network gels. Experimental and DFT results allowed the elaboration of the specific non-covalent co-assembly mechanism for DN gel formation and DOX loading. The DN gels were formed by co-assembly driven by H-bond and π-π stacking interactions and then strengthened by Ca2+-coupling. Most DOX molecules co-assembled with Fmoc-F and alginate through π-π stacking and H-bond interactions (DOX-I), with a few free DOX molecules (DOX-II) left. Proven by the release dynamics test, DOX was released through a diffusion-erosion process, in an order of DOX-I first and then DOX-II. This work suggests that non-covalent co-assembly is a useful technique for effective material strengthening and drug delivery.

Formulation of 1% α-mangostin in orabase gel induces apoptosis in oral squamous cell carcinoma.

BACKGROUND: Plant-derived compounds have chemopreventive properties to be used as alternative medicine. Pericarp of Mangosteen (Garcinia mangostana Linn.), a tropical fruit in Southeast Asia contains a phytochemical α-mangostin (α-MG) that demonstrates potent anticancer effects against various types of cancer. α-MG has been reported to be the most effective agent in human cancer cell lines. The objectives of this study were to develop oral gel formulations containing α-MG and determine their (1) anticancer activity, (2) anti-HPV-16 and antimicrobial activities, (3) nitric oxide (NO) inhibitory activity, and (4) wound healing effect. METHODS: Formulations of oral gel containing α-MG were developed. Anticancer activity on SCC-25 was assessed. Apoptotic induction was determined using flow cytometry technique. Antiviral activity against HPV-16 pseudovirus and antimicrobial activity against S. mutans, P. gingivalis and C. albicans were investigated. NO inhibition was carried out. Fibroblast cell migration was determined by in vitro scratch assay. RESULTS: The formulation of 1% α-MG in orabase gel demonstrated anticancer activity by promoting apoptosis in SCC-25. The induction of apoptotic activity was dose dependent with pronounced effect in late apoptosis. The formulation appeared to reduce cell viability of oral keratinocytes (OKC). At CC50 it showed an inhibition against HPV-16 pseudovirus infection. The formulation had no antimicrobial activity against S. mutans, P. gingivalis and C. albicans. No significant NO inhibitory activity and wound healing effects were found. CONCLUSIONS: 1% α-MG in orabase gel exhibited anticancer activity by inducing apoptosis although low level of cytotoxicity observed in OKC was present. The appropriate carrier for novel nano-particles targeting cancer cells should be further investigated.

The decomposition rate and bleaching efficacy of in-office bleaching gels with different pHs: a randomized controlled trial.

BACKGROUND: To evaluate the decomposition rate of active hydrogen peroxide (HP) and bleaching efficacy during in-office bleaching using high-concentration HP gels with different pHs. METHOD: A randomized, parallel, double-blind controlled trial was conducted with 40 volunteers randomized into four groups (pH 5.4; pH 7.0; pH 7.7, and pH 8.0). During the first session in-office bleaching, approximately 0.01 g of the gel was collected and titrated with potassium permanganate to obtain the concentration of active HP and pH values were measured using an electrode. Bleaching efficacy was assessed using a spectrophotometer [∆Eab, ∆E00, and WID], Vita Classical and Vita Bleachedguide scales [∆SGU]. The decomposition rate of HP concentration and pH values change were calculated using ANOVA one-way. The bleaching efficacy was assessed using two-way repeated measures ANOVA. Tukey's test was applied as a post-hoc test (p < 0.05). RESULTS: All gels experienced decreasing HP concentration over time. pH 5.4 gel showed greatest reduction after 50 min (p < 0.001). pH 8.0 and 7.7 gels remained stable; pH 5.4 remained acidic, while pH 7.0 turned acidic (p < 0.001). No significant difference in bleaching degree was observed among gels. They all showed a similar and clinically important color change after two clinical sessions, remained stable 1-month post-treatment (p > 0.05). CONCLUSIONS: All bleaching gels kept at least 70% of their HP content after 50 min, suggesting that there is a surplus of HP. They provided similar whitening efficacy 1-month after bleaching. PRACTICAL IMPLICATIONS: It is possible that lower HP concentrations may be equally effective in achieving desired results while reducing the potential for side effects. CLINICAL TRIAL REGISTRY NAME: RBR-35q7s3v.

Preparation and Screening of SRB Gel Particles Used for Deep Purification of Acid Mine Drainage.

The progressive decline of the coal industry necessitates the development of effective treatment solutions for acid mine drainage (AMD), which is characterized by high acidity and elevated concentrations of heavy metals. This study proposes an innovative approach leveraging sulfate-reducing bacteria (SRB) acclimated to contaminated anaerobic environments. The research focused on elucidating the physiological characteristics and optimal growth conditions of SRB, particularly in relation to the pH level and temperature. The experimental findings reveal that the SRB exhibited a sulfate removal rate of 88.86% at an optimal temperature of 30 °C. Additionally, SRB gel particles were formulated using sodium alginate (SA) and carboxymethyl cellulose (CMC), and their performance was assessed under specific conditions (pH = 6, C/S = 1.5, T = 30 °C, CMC = 4.5%, BSNa = 0.4 mol/L, and cross-linking time = 9 h). Under these conditions, the SRB gel particles demonstrated an enhanced sulfate removal efficiency of 91.6%. Thermal analysis via differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) provided further insights into the stability and properties of the SRB gel spheres. The findings underscore the potential of SRB-based bioremediation as a sustainable and efficient method for AMD treatment, offering a novel and environmentally friendly solution to mitigating the adverse effects of environmental contamination.

Optimizing the feasibility of polyvinyl alcohol-potassium iodine gel for medical dosimeter.

This work aims to improve the post stabilty of reusable potassium iodide hydrogel dosimter. A reusable and low-cost radiochromic dosimeter containing a gel matrix of polyvinyl alcohol, potassium iodide dye, froctose as reducing agent and glutaraldehyde as cross-linking agent was developed for dose calibration in radiotherapy. The gel samples were exposed to different absorbed doses using a medical linear acceleration. UV-vis Spectrophotometry was utilized to investigate the changes in optical-properties of irradiated gels with regard to peak wavelength of 353 nm. The stability of the gel (one of the most limitation of using this dosimeter) was improved significantly by the addition of certain concentrations of dimethyl sulfoxide. The two-dimensional optical imaging system of charge-coupled-device (CCD) camera with a uniform RGB light-emitting-diode (LED) array source was used for diffusion coefficient purpose using two dimensional gel template. The value of diffusion coefficient reported is significant and highly reduced compared with other dosimeters reported in the literatures. Moreover, heating the improved gels to certain temperatures results in resetting their optical properties, which makes it possible to reuse for multiple times.

Anti-quorum sensing activity of α-amidoamides against Agrobacterium tumefaciensNT1: Insights from molecular docking and dynamic investigations to synergistic approach of metronidazole release from gel formulations.

A unique approach is imperative for the development of drugs aimed at inhibiting various stages of infection, rather than solely focusing on bacterial viability. Among the array of unconventional targets explored for formulating novel antimicrobial medications, blocking the quorum-sensing (QS) system emerges as a highly effective and promising strategy against a variety of pathogenic microbes. In this investigation, we have successfully assessed nine α-aminoamides for their anti-QS activity using Agrobacterium tumefaciensNT1 as a biosensor strain. Among these compounds, three (2, 3and, 4) have been identified as potential anti-QS candidates. Molecular docking studies have further reinforced these findings, indicating that these compounds exhibit favorable pharmacokinetic profiles. Additionally, we have assessed the ligand's stability within the protein's binding pocket using molecular dynamics (MD) simulations and MMGBSA analysis. Further, combination of antiquorum sensing properties with antibiotics viaself-assembly represents a promising approach to enhance antibacterial efficacy, overcome resistance, and mitigate the virulence of bacterial pathogens. The release study also reflects a slow and gradual release of the metronidazole at both pH 6.5 and pH 7.4, avoiding the peaks and troughs associated with more immediate release formulations.

Mechanical release of homogenous proteins from supramolecular gels.

A long-standing challenge is how to formulate proteins and vaccines to retain function during storage and transport and to remove the burdens of cold-chain management. Any solution must be practical to use, with the protein being released or applied using clinically relevant triggers. Advanced biologic therapies are distributed cold, using substantial energy, limiting equitable distribution in low-resource countries and placing responsibility on the user for correct storage and handling. Cold-chain management is the best solution at present for protein transport but requires substantial infrastructure and energy. For example, in research laboratories, a single freezer at -80 °C consumes as much energy per day as a small household1. Of biological (protein or cell) therapies and all vaccines, 75% require cold-chain management; the cost of cold-chain management in clinical trials has increased by about 20% since 2015, reflecting this complexity. Bespoke formulations and excipients are now required, with trehalose2, sucrose or polymers3 widely used, which stabilize proteins by replacing surface water molecules and thereby make denaturation thermodynamically less likely; this has enabled both freeze-dried proteins and frozen proteins. For example, the human papilloma virus vaccine requires aluminium salt adjuvants to function, but these render it unstable against freeze-thaw4, leading to a very complex and expensive supply chain. Other ideas involve ensilication5 and chemical modification of proteins6. In short, protein stabilization is a challenge with no universal solution7,8. Here we designed a stiff hydrogel that stabilizes proteins against thermal denaturation even at 50 °C, and that can, unlike present technologies, deliver pure, excipient-free protein by mechanically releasing it from a syringe. Macromolecules can be loaded at up to 10 wt% without affecting the mechanism of release. This unique stabilization and excipient-free release synergy offers a practical, scalable and versatile solution to enable the low-cost, cold-chain-free and equitable delivery of therapies worldwide.

Preparation and in vivo and ex vivo studies of sirolimus nano-in-situ gel ophthalmic formulation.

Sirolimus (SR) is a macrolide with antifungal and antitumor immunosuppressant properties, classified as a selective inhibitor of mammalian target of rapamycin (mTOR). In this study, an ionic in situ gel of SR (SR-SUS-ISG) was formulated using gellan gum, exhibiting stability regardless of temperature and pH variations, causing minimal irritation. Harnessing the physiological conditions of the eye, SR-SUS-ISG underwent gelation upon contact with ions, increasing drug viscosity and prolonging retention on the ocular surface. Concurrently, SR-SUS-ISG displayed favorable shear dilution properties, reducing viscosity at ambient temperature, enhancing fluidity, and facilitating convenient packaging and transport. Biocompatibility assessments on both human corneal epithelial cells and rabbit eyes demonstrated that SR-SUS-ISG could well be tolerated. Pharmacokinetic investigations in rabbit ocular aqueous humor revealed sustained release, improved corneal penetration, and enhanced bioavailability. Additionally, in a rat corneal alkali burn model, SR-SUS-ISG exhibited inhibitory effects on corneal neovascularization, associated with decreased levels of the inflammatory factors VEGF and MMPs. These findings suggested that SR-SUS-ISG held promise as an effective ocular drug delivery system.

Stabilization of Non-Native Folds and Programmable Protein Gelation in Compositionally Designed Deep Eutectic Solvents.

Proteins are adjustable units from which biomaterials with designed properties can be developed. However, non-native folded states with controlled topologies are hardly accessible in aqueous environments, limiting their prospects as building blocks. Here, we demonstrate the ability of a series of anhydrous deep eutectic solvents (DESs) to precisely control the conformational landscape of proteins. We reveal that systematic variations in the chemical composition of binary and ternary DESs dictate the stabilization of a wide range of conformations, that is, compact globular folds, intermediate folding states, or unfolded chains, as well as controlling their collective behavior. Besides, different conformational states can be visited by simply adjusting the composition of ternary DESs, allowing for the refolding of unfolded states and vice versa. Notably, we show that these intermediates can trigger the formation of supramolecular gels, also known as eutectogels, where their mechanical properties correlate to the folding state of the protein. Given the inherent vulnerability of proteins outside the native fold in aqueous environments, our findings highlight DESs as tailorable solvents capable of stabilizing various non-native conformations on demand through solvent design.

Formulation, Optimization and In-Vivo Characterization of Thermosensitive In-Situ Nasal Gel Loaded with Bacoside a for Treatment of Epilepsy.

The intranasal route has demonstrated superior systemic bioavailability due to its extensive surface area, the porous nature of the endothelial membrane, substantial blood flow, and circumvention of first-pass metabolism. In traditional medicinal practices, Bacopa monnieri, also known as Brahmi, is known for its benefits in enhancing cognitive functions and potential effects in epilepsy. This study aimed to develop and optimize a thermosensitive in-situ nasal gel for delivering Bacoside A, the principal active compound extracted from Bacopa monnieri. The formulation incorporated Poloxamer 407 as a thermogelling agent and HPMC K4M as the Mucoadhesive polymer. A 32-factorial design approach was employed for Optimization. Among the formulations. F7 exhibited the most efficient Ex-vivo permeation through the nasal mucosa, achieving 94.69 ± 2.54% permeation, and underwent a sol-gel transition at approximately 30.48 °C. The study's factorial design revealed that gelling temperature and mucoadhesive strength were critical factors influencing performance. The potential of in-situ nasal Gel (Optimized Batch-F7) for the treatment of epilepsy was demonstrated in an in-vivo investigation using a PTZ-induced convulsion model. This formulation decreased both the occurrence and intensity of seizures. The optimized formulation F7 showcases significant promise as an effective nasal delivery system for Bacoside A, offering enhanced bioavailability and potentially increased efficacy in epilepsy treatment.

Green micellar factorial design optimized first derivative synchronous spectrofluorimetric method for tripelennamine and diphenhydramine determination in pharmaceutical gel.

A green micellar synchronous spectrofluorimetric method was developed and validated for simultaneous determination of tripelennamine hydrochloride and diphenhydramine in bulk and combined pharmaceutical formulation. Synchronous fluorescence of tripelennamine hydrochloride and diphenhydramine was determined using Δλ = 60 nm. The first derivative of synchronous fluorescence was computed to resolve overlap in the synchronous fluorescence spectra. Tripelennamine hydrochloride was quantified at 375 nm, whereas diphenhydramine was quantified at 293 nm; each is the zero-crossing point of the other. As diphenhydramine exhibited weak native fluorescence, micelle enhancement upon incorporation of sodium dodecyl sulfate was considered. Two-level full factorial design was carried out to optimize experimental parameters. Optimum conditions involved using SDS (2% w/v) along with Teorell and Stenhagen buffer (pH 9). The method was found to be linear over the range 0.2-4.5 and 0.2-5 µg/mL for tripelennamine and diphenhydramine, respectively, with limits of detection 0.211 and 0.159 µg/mL. The method was successfully applied for simultaneous determination of tripelennamine hydrochloride and diphenhydramine in laboratory-prepared gel containing all possible excipients with mean percent recoveries ±SD 100.59 ± 0.79 and 98.99 ± 0.98 for tripelennamine hydrochloride and diphenhydramine, respectively. The proposed method was proved to be eco-friendly using different greenness assessment tools.