In-vivo Studies Research Articles

Evaluation of Antiurolithiatic Effects of Moringa oleifera Lam. Leaves Extract: In-vitro, in-silico and in-vivo Approaches.

Objective: Moringa oleifera Lam. (Moringaceae), has traditionally been used for various renal diseases including urolithiasis. Considering the therapeutic and nutritional values, the present study was designed to investigate the antiurolithiatic potential of M. oleifera leaves through in-vitro, in-silico and in-vivo approaches. Methods: Methanolic aqueous extract of M. oleifera. leaves (MoL.Cr) was prepared and screened for phytoconstituents through FTIR and HPLC analysis, while antioxidant potential was determined by DPPH assay. Crystal nucleation, aggregation and growth assays were carried out to ascertain the in-vitro inhibitory effects of MoL.Cr. Molecular docking was performed to analyze the interactions between phytoconstituents and targeted proteins (Glycolate oxidase, Albumin and Tamm-Horsfall). Whereas, ethylene glycol-induced urolithiasis model (1% ammonium chloride +0.75% ethylene glycol) was used for in-vivo study. Presence of alkaloids, phenols, glycosides and flavonoids was confirmed by FTIR and HPLC analysis. Results: MoL.Cr significantly inhibited the CaOx crystal nucleation, aggregation as well as growth and normalized urinary and serum parameters. Histological studies showed that MoL.Cr significantly restored hyperoxaluria-induced irregular epithelial lining, interstitial inflammation and dilated proximal tubules. Conclusions: Thus, M. oleifera demonstrated marked stone inhibiting potential which can be due to its antioxidant, lowering of urinary concentration of stone forming constituents and anti-crystallization effects.

Identification of distinct stool metabolites in women with endometriosis for non-invasive diagnosis and potential for microbiota-based therapies.

Endometriosis, a poorly studied gynecological condition, is characterized by the presence of ectopic endometrial lesions resulting in pelvic pain, inflammation, and infertility. These associated symptoms contribute to a significant burden, often exacerbated by delayed diagnosis. Current diagnostic methods involve invasive procedures, and existing treatments provide no cure. Microbiome-metabolome signatures in stool samples from individuals with and without endometriosis were determined using unbiased metabolomics and 16S bacteria sequencing. Functional studies for selected microbiota-derived metabolites were conducted invitro using patient-derived cells and invivo by employing murine and human xenograft pre-clinical disease models. We discovered a unique bacteria-derived metabolite signature intricately linked to endometriosis. The altered fecal metabolite profile exhibits a strong correlation with that observed in inflammatory bowel disease (IBD), revealing intriguing connections between these two conditions. Notably, we validated 4-hydroxyindole, a gut-bacteria-derived metabolite that is lower in stool samples of endometriosis. Extensive invivo studies found that 4-hydroxyindole suppressed the initiation and progression of endometriosis-associated inflammation and hyperalgesia in heterologous mouse and in pre-clinical models of the disease. Our findings are the first to provide a distinct stool metabolite signature in women with endometriosis, which could serve as stool-based non-invasive diagnostics. Further, the gut-microbiota-derived 4-hydroxyindole poses as a therapeutic candidate for ameliorating endometriosis. This work was funded by the NIH/NICHD grants (R01HD102680, R01HD104813) and a Research Scholar Grant from the American Cancer Society to R.K.

Anticancer effects of emetine against cisplatin resistant pancreatic cancer cells via activation of Cyto-c/Caspase-9/Caspase-3/Bax/Bad axis

This investigation examines the potential pharmacotherapeutic efficacy of emetine, a natural alkaloid, against pancreatic ductal carcinoma, utilizing the PaCa3 cell line as a model. Employing a multifaceted approach, the study explores emetine's impact on cell viability, clonogenic potential, and apoptotic pathways, unravelling its molecular mechanisms. Additionally, an in-vivo assessment is conducted to evaluate emetine's antitumor efficacy against PaCa3 xenografts. Under standard conditions, PaCa3 cells were treated with varying emetine concentrations and subjected to MTT, clonogenic, DAPI, AO/EB, Annexin V-FITC/PI, and Western blot assays. In-vivo experiments involved the administration of emetine to female nude mice with PaCa3 xenografts, with subsequent measurement of tumor weight and volume. Statistical analyses included Tukey-test and ANOVA. Emetine demonstrated a significant and dose- and time-dependent cytotoxic effect on PaCa3 cells, reducing viability from 98% to 8% (***p<0.001). Clonogenic assay indicated a substantial inhibition of colony formation. DAPI staining revealed nuclear chromatin condensation, while AO/EB staining indicated heightened apoptosis. Annexin V-FITC/PI assay exhibited a dose-dependent decrease in normal cell viability and an increase in apoptotic events. Western blot analysis showcased concentration-dependent downregulation of anti-apoptotic Bcl-2 and upregulation of pro-apoptotic markers. In-vivo experiments illustrated a dose-dependent reduction in tumor weight (5 g to 1.6 g) and volume (2400 mm³ to 844 mm³) with emetine treatment. In conclusion, emetine emerges as a potent anticancer agent against pancreatic ductal carcinoma, exhibiting cytotoxicity, clonogenic inhibition, and apoptotic induction in PaCa3 cells. The in-vivo study further highlights its promising therapeutic potential, laying the groundwork for future clinical studies in pancreatic cancer treatment.

Impact of oil type on the development and oral bioavailability of self-nanoemulsifying drug delivery systems containing simvastatin

The aim of this work is to develop and evaluate self-nanoemulsifying drug delivery systems (SNEDDS) containing simvastatin to increase its oral bioavailability. Formulation EO 5 (Ethyl oleate 9.3% w/w: Tween 80 49.4% w/w: Propylene glycol 39.3% w/w) and Formulation CL 14 (Clove oil 54.3% w/w: Tween 80 34.4% w/w: Transcutol-P 9.3% w/w) were thoroughly studied. They showed emulsification time less than 1 min, droplet size in the nanometric range, and almost a complete drug release after 2 h. The in-vitro dissolution profile of both formulations was found to be significant in comparison to the pure drug in pH 1.2 and 7.4 buffers (P < 0.0001). Furthermore, they demonstrated superior anti-hyperlipidemic activity in comparison to simvastatin suspension (10 mg/kg/day). In order to investigate the impact of oil type on oral bioavailability, the selected formulations have been examined in terms of the in-vivo pharmacokinetic study, and formulation EO 5 was found to have higher bioavailability. After oral administration of a single dose (40 mg/kg) of simvastatin-loaded SNEDDS (CL14 and EO 5), a 1.5-fold and 1.95-fold increase in bioavailability were observed, respectively, as compared to simvastatin suspension. Hence, the results indicated that the developed SNEDDS could enhance the therapeutic efficacy and oral bioavailability of simvastatin.

The relationship between CYP2C9 gene polymorphisms and azilsartan metabolism in vitro

ABSTRACT Background The gene polymorphisms of the CYP2C9, as well as the substrate specificity of the enzyme, result in different clearances for different substrates by CYP2C9 variants. Research designand methods The CYP2C9 wild type and 38 CYP2C9 variants, expressed in insectmicrosomes, were incubated with azilsartan. The resulting metabolite,O-desethyl azilsartan, was determined by HPLC-MS/MS. The enzyme kineticparameters of the 38 variants were calculated and compared with the wild type.Subsequently, we selected CYP2C9*1, *2, and *3 as target proteins for molecular docking with azilsartan to elucidate the mechanisms underlying changes in enzyme function. Results Compared with CYP2C9*1, three variants (CYP2C9*29, *39, and *49) exhibited markedlyincreased CLint values (from 170%-275%, *p < 0.05), whereas 28 variants exhibited significantly decreased CLint values (from 3-63%,*p < 0.05). The molecular docking results showed that the binding energy of CYP2C9*2 and *3 was lower than that of the wild type. Conclusion Thisassessment revealed the effect of CYP2C9 gene polymorphisms on azilsartan metabolism, establishing a theoretical basis for further in-vivo studies and clinical applications. This study will help expand the database of CYP2C9 gene-drug pairs and identify appropriate treatment strategies for azilsartan, contributing to the field of precision medicine.

Distortion Assessment of Different Materials in Full-Arch Dentate Impressions in Relation to Operator Experience: A Comparative In Vivo Study.

To evaluate the distortion probability in impressions of completely dentate arches when different impression materials are used in relation to operator experience. A total of 28 students (Group A) and 7 dentists (Group B) performed three maxillary impressions on 28 participants, each using vinyl siloxane ether (VSE), polyether (PE), and irreversible hydrocolloid (IHC). Gypsum master casts were fabricated and subsequently digitized. Intraoral scans were taken as a control. Differences between master casts and intraoral scans were visualized with heatmaps, and planar deviations were investigated. If planar deviations > 120 μm were found, the impression was rated as 'distorted.' An additional superimposition using the casts from VSE or PE was performed to confirm the presence of distortions. The relative number of surfaces with distortions in each impression was calculated. The procedure was repeated for a distortion threshold of 500 μm. The statistical analyses included repeated measures ANOVA (RMA) and post hoc tests (α < .05). When 120 μm was considered as the threshold for distortions, IHC impressions showed higher distortion probability than PE impressions in Group A (P &#61; .003) and Group B (P < .0001). In Group B, PE showed a lower distortion probability than VSE (P &#61; .02). There was no significant difference between the study groups (P &#61; .42). Considering 500 μm as a threshold for distortions, there was no difference between impression materials (P &#61; .17) or study groups (P &#61; .53). There were no statistically significant differences in relation to operator experience. Different impression materials had a significant impact on distortion probability. PE impressions showed the lowest distortion probability.

Can shoe tip modifications on safety shoes reduce the braking forces in a trip-simulating, free-body shoe collision test?

Tripping often results in injury, especially in occupational settings, leading to both loss in production and increased medical expenses. Trips may occur over small perturbations, as low as 5 mm, making it almost impossible to provide effective safety precautions in many occupational settings. This explorative study evaluated the mechanical effects of collisions applied to three novel trip-reducing elements placed on the tip of a safety shoe. The assessment was conducted using a new mechanical free-body collision test, to analyse how the braking forces were affected by the trip-reducing elements. The elements tested showed a decrease of up to 83% in peak braking force and 89% in braking impulse suggesting a possible reduction in the risk of fall after tripping. Still, in-vivo studies are warranted to test if such trip-reducing elements can minimise the risk of falls in settings mimicking real life.

Development and Characterization of Gingerol-Assisted Silver Nanoparticle and Chitosan Alginate Membrane for Antibacterial and Wound Healing Activity.

This study synthesized and characterized gingerol-loaded silver nanoparticles (Ag-NPs), which were incorporated into chitosan-alginate (Cs/Alg) films for advanced wound care applications. Gingerol was isolated with a 9.81% yield, forming pale-yellow needle-shaped crystals with a melting point of 32ºC. The purity and structure of gingerol were confirmed through thin-layer chromatography (TLC), UV-visible, fourier-transform infrared spectroscopy (FTIR), and high-performance liquid chromatography (HPLC) analyses. The synthesized Ag-NPs, particularly from the GN3 batch, exhibited a small particle size (36.52 ± 3.52 nm), high stability (zeta potential of -23.20 mV), and notable encapsulation efficiency (76.35%) and yield (74.11%). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses revealed their spherical and smooth morphology. Stability tests over three months showed no substantial changes in particle size, ZP, or %EE. The Cs/Alg films demonstrated appropriate thickness, weight, water uptake, and pH changes, with GN-CM4 showing the best performance. In-vitro drug release studies indicated increased release rates, especially for GN-CM4, which also exhibited the highest antibacterial activity. In-vivo studies on excision and burn wound models showed that GN-CM4 promoted complete wound closure by day 21, enhanced hydroxyproline levels, reduced myeloperoxidase content, and facilitated superior tissue regeneration. These findings underscore the potential of gingerol-loaded Ag-NPs in enhancing wound healing through their anti-inflammatory and antibacterial properties.

In-vivo Evaluation Methods for Preparation of Ophthalmic In-situ Gel

The eye is a vital component of the human sensory system, but various things can pose a threat to its cleanliness and well-being. An in-situ ophthalmic gel is one of the preparations developed to optimize the pharmacological activity in the eye. This formulation is intended to extend the drug's duration in the eye. An assessment is necessary to guarantee its occurrence and mitigate any adverse repercussions. The literature search conducted in this evaluation focused on an in-vivo study, enabling the collection of various pharmacokinetic data, including Cmax, Tmax, area under curve (AUC), and mean residence time (MRT). The polymer is an essential element in this inquiry, so the selection must be accurate according to the results of the literature review. The most effective method is high-performance liquid chromatography (HPLC), and the most effective polymer is a composite polymer formed by combining different types of polymers, such as Pluronic F127 and carbopol, pectin and thiolate, poloxamer and carbopol, and gellan gum and hydroxyethylcellulose. Aside from the polymer mixture, the poloxamer solution has the potential to produce highly positive results.

Design, Development and Characterization of Gastroretentive Floating Tablet of Levofloxacin using Natural Polymer Peanut Husk.

In the present study, levofloxacin gastroretentive floating tablet (GRFT) was formulated using peanut husk powder as a natural release modifier for providing sustained drug delivery at the stomach to effectively treat infections. Preformulation studies such as UV analysis and drug excipients study using Fourier-transform infrared (FTIR) were performed. Peanut husk powder was prepared by crushing and grinding the dried peanut husk. The GRFT formulations (GRFT1- GRFT9) were formulated using the direct compression method with varied concentrations having peanut husk powder, HPMCK4M and carbapol 934, along with other ingredients. Formulations were characterized based on the pre-compressional parameter and post-compressional parameters. The results for GRFT5 were found to be best among all batches as it showed sustained %drug release of 89.52 ± 0.3% upto 12 hours and it revealed enhanced therapeutic performance of the drug. However, in-vivo study needs to be performed for a better comparison of data with in-vitro results.

Tofacitinib Citrate-Loaded Topical Gel for the Treatment of Rheumatoid Arthritis: Formulation and In-vitro-In-vivo Characterization.

This study aims to create and assess the anti-arthritic activity of tofacitinib citrate (TC) as a topical gel formulation. Using the gelling agent Carbopol 980 P, seven gel formulations were formed. The gel formulations were assessed for pH, drug content, spreadability, homogeneity, and in-vitro diffusion profile. Out of all the formulations, G7 exhibited superior release characteristics (99.1%) in comparison to the other formulations. The DSC research revealed a strong endothermal peak at 214.17°C and demonstrated an interaction with the excipients taken into consideration in this investigation. While carrying out the in-vivo study, formulation G7 successfully reduced inflammation induced by CFA. Ultimately, the optimal formulation for the “G7” can be determined &amp; successfully treats inflammation associated with arthritis. As per stability studies, it was specified that there are no such major changes in the long-term and accelerated stability testing study.

Formulation and Evaluation of Sustained Release Dosage Form of Venlafaxine Hydrochloride for Enhanced Treatment of Neurodisorders

In the present study, we have designed and developed a sustained-release tablet formulation of Venlafaxine Hydrochloride. The optimized formulation was then subjected to various evaluation parameters. The formulation of venlafaxine hydrochloride sustained release tablets with a dosage of 500 mg included the utilization of several hydrophilic polymers, including jackfruit mucilage, HPMC K4, and PVPK30, as release retardants. This was done to extend the duration of drug release to 12 hours. The formulation features, including pre-compression and post-compression investigations, were conducted individually according to established protocols. The tablets were determined to be compliant in terms of weight uniformity, hardness, thickness, diameter, friability, and drug content. Separate in-vitro dissolution studies were done for both tablets. The venlafaxine hydrochloride SR formulation F18 was optimized to provide the desired release profile for up to 12 hours. The Venlafaxine Hydrochloride SR formulation was optimized and exhibited zero-order release kinetics. The stability studies conducted under accelerated conditions at a temperature of 40 ± 2°C and a relative humidity of 75 ± 5% yielded good results. The study indicated that the sustained release administration of Venlafaxine HCl is potentially efficacious. It reduces the frequency at which the patient has to take medication and improves patient adherence. Our objective is to conduct in-vivo pharmacokinetic studies of the formulation to verify the drug’s entry into the systemic circulation.

In-vitro and in-vivo comparative studies of treatment effects on enamel demineralization during orthodontic therapy: implications for clinical early-intervention strategy

ObjectivesThis study aimed to investigate if CPP-ACP / infiltrating resin was superior in treating enamel demineralization during orthodontic therapy compared with fluoride varnish, in order to provide early-intervention implications for dental professionals.Materials and methodsIn the in-vitro study, premolars were grouped into four: remineralization with fluoride varnish / CPP-ACP, sealing with infiltrating resin, and negative control. Experimental demineralization of enamel surfaces was analyzed using techniques of QLF, SEM, EDS and micro-hardness testing. An in-vivo intervention study was conducted on patients randomly assigned into three groups. At the baseline and every-3-month follow-up, QLF parameters were compared temporally and parallelly to yield potential implications for promotion in clinical practice.ResultsThe in-vitro study performed on 48 experimental tooth surfaces demonstrated that sealing with infiltrating resin reduced enamel surface porosity and increased surface micro-hardness significantly. In the in-vivo intervention study on 163 tooth surfaces, it was suggested that for those who meet the criteria of -10 < ΔF < -6 and − 1000 < ΔQ < -20 at the baseline, all these treatment methods could achieve acceptable outcomes; with the rising of absolute values of ΔF and ΔQ, sealing with infiltrating resin showed more evident advantages.ConclusionFor enamel demineralization during orthodontic therapy, all the treatment methods involved in this study showed acceptable effectiveness but had respective characteristics in treatment effects. QLF parameters could be used as indicators for clinical early-intervention strategy with regards to this clinical issue.Clinical relevanceWith QLF parameters, clinical early-intervention strategy for enamel demineralization during orthodontic therapy could be optimized.

Experimental and Theoretical Studies for Noncovalent Interactions Analysis of 2-Phenyl Imidazole Derivative: Perspective for Anti-Inflammatory Activity

Synthesis of 2-Phenyl imidazole derivative has been carried out for the studies of quantitative non-covalent interactions and anti-inflammatory activity. Hirshfeld surface analysis, crystal structure, and non-covalent interaction computation have all been used to do quantitative investigations of non-covalent interactions. The intermolecular interactions calculations have been done with crystalexplorer 17. Further, anti-inflammatory activities of synthesized molecules were evaluated by molecular docking studies through autodock vina and in-vivo studies through carrageenan rat model. The molecular docking and in-vivo studies revealed that all molecules have shown significant anti-inflammatory activity, compared to standard drugs nimesulide.

A dual-layer nano dressing with enhanced antimicrobial and healing properties via sesame nanoemulgel with efficient levofloxacin delivery for wound management

Creating suitable wound dressings is considered a promising approach for treating severe skin injuries, as they can provide the environment for healing and protection against infection. The optimum wound dressing should possess biocompatibility, high absorbency, antimicrobial activity, breathability, and mechanical strength. So, in this study, we created a two-layer dressing that includes a surface layer composed of xanthan, polyvinyl alcohol, and sesame oil, as well as a nanofibrous sublayer that contains polyvinyl alcohol, collagen, levofloxacin, and sesame oil nanoemulsion (Video 1). This dual structure is designed to offer antimicrobial properties and facilitate wound healing while having suitable physical stability. The films showed desirable morphological features and significantly increased flexibility (less than 1000). These features were respectively proven through scanning electron microscopy and tensile strength. Laboratory investigations were conducted to examine the precise compatibility and anti-inflammatory features. According to the obtained results, the nanosystems showed compatibility with hemolysis below 5 percent and by adding sesame oil to the films, their anti-inflammatory properties (88 ± 0.19 %) and blood compatibility (1.3507 ± 0.20) increased. In-vivo studies using the rat skin defect model showed that the dressings significantly accelerate the closure of skin wounds and enhance the reconstruction of skin appendage structures. The therapeutic effect resulted from reducing inflammatory factors, and the film's antimicrobial properties effectively prevent the growth of harmful microorganisms. In conclusion, the study suggests that the new nano-biocomposite films suit wound management.

Solid Self Nano-Emulsifying Drug Delivery System of Dasatinib: Optimization, In-vitro, Ex-vivo and In-vivo assessment.

Aim: Dasatinib (DST) is an oral tyrosine kinase inhibitor with poor aqueous solubility. To outwit this issue, a solid self-nano emulsifying drug delivery system (S-SNEDDS) of DST was formulated.Methods: I-optimal mixture design was used for optimization of DST-loaded SNEDDS using Linalool, Cremophor RH40 and Transcutol P. S-SNEDDS underwent physicochemical characterization, in-vitro release and ex-vivo permeation, cell-based assays and pharmacokinetic study.Results: DST-S-SNEDDS showed globule size and PDI of 141.53±5.371nm and 0.282±0.020, respectively. DST-S-SNEDDS revealed significantly lower IC50 (1.825μg/mL) than free DST (7.298μg/mL) in MDA-MB-231. In-vivo pharmacokinetic study revealed 1.94-fold increment in AUC0-t for the DST-S-SNEDDS group than free DST.Conclusion: S-SNEDDS could be promising approach for improving bioavailability and efficacy of DST.

Bioactive Properties of Enzymatic Gelatin Hydrolysates Based on In Silico, In Vitro, and In Vivo Studies.

This current study aims to analyze the potential bioactivities possessed by the enzymatic hydrolysates of commercial bovine, porcine, and tilapia gelatins using bioinformatics in combination with in vitro and in vivo studies. The hydrolysate with superior inhibition of angiotensin converting enzyme (ACE) activity was used to treat the D-galactose (DG)-induced amnesic mice. In silico digestion of the gelatins led to the identification of peptide sequences with potential antioxidant, ACE-inhibitory, and anti-amnestic properties. The results of in vitro digestion revealed that the <1 kDa peptide fraction of porcine gelatin hydrolysate obtained after 1 h digestion with papain (PP) (PP1, <1 kDa) potently inhibited ACE, acetylcholinesterase, and prolyl endopeptidase activities at 87.42%, 21.24%, and 48.07%, respectively. Administering the PP1 to DG-induced amnesic mice ameliorated the spatial cognitive impairment and Morris water maze learning abilities. The dentate area morphology in the PP1-treated mice was relatively similar to the control group. In addition, PP1 enhanced the antioxidant capacity in the DG-induced amnesic mice. This study suggests that PP1 could serve as a potential treatment tool against oxidative stress, hypertension, and neurodegenerative diseases.

Breast cancer cell derived exosomes reduces glycolysis of activated CD8 + T cells in a AKT-mTOR dependent manner.

Cytotoxic CD8+ T cells plays a pivotal role in the adaptive immune system to protect the organism against infections and cancer. During activation and response, T cells undergo a metabolic reprogramming that involves various metabolic pathways, with a predominant reliance on glycolysis to meet their increased energy demands and enhanced effector response. Recently, extracellular vesicles (EVs) known as exosomes have been recognized as crucial signaling mediators in regulating the tumor microenvironment (TME). Recent reports indicates that exosomes may transfer biologically functional molecules to the recipient cells, thereby facilitate cancer progression, angiogenesis, metastasis, drug resistance, and immunosuppression by reprogramming the metabolism of cancer cells. This study sought to enlighten possible involvement of cancer-derived exosomes in CD8 + T cell glucose metabolism and discover a regulated signalome as a mechanism of action. We observed reduction in glucose metabolism due to downregulation of AKT/mTOR signalome in activated CD8 + T cells after cancer derived exosome exposure. In-vivo murine breast tumor studies showed better tumor control and antitumor CD8 + T cell glycolysis and effector response after abrogation of exosome release from breast cancer cells. Summarizing, the present study establishes an immune evasion mechanism of breast cancer cell secreted exosomes that will act as a foundation for future precision cancer therapeutics.

Washing Illness Away: A Systematic Review of the Impact of Nasal Irrigation and Spray on COVID-19.

Nasal irrigation is a common treatment for sinonasal disorders; however, it is unknown if it can reduce SARS-CoV-2 nasopharyngeal viral load (NVL). This systematic review investigated the efficacy of nasal irrigation with saline, povidone iodine (PVP-I), and intranasal corticosteroids (INCS) at reducing SARS-CoV-2 NVL and transmissibility. Databases including Embase, MEDLINE, Web of Science, and ClinicalTrials.gov. A systematic review was completed with pre-defined search criteria using keywords related to nasal irrigation and COVID-19 from 1946 through January 2024. This review followed PRISMA reporting guidelines and was registered on PROSPERO. Only in-vivo studies testing nasal irrigation with either saline, PVP-I, or INCS for reducing NVL were included. Nine out of ten studies on saline-based solutions reported positive effects in reducing NVL, with benefits noted in earlier time to negative nasopharyngeal PCR and a greater decline in NVL during early study time points, compared with controls. Isotonic and hypertonic saline mediums were found to be effective with three studies demonstrating enhanced efficacy with additives. Four out of seven studies on PVP-I showed a positive effect on reducing NVL, but results were heterogenous. Four studies demonstrated reduction of transmission with saline or PVP-I. No studies were found on INCS. Saline nasal irrigation showed the best efficacy in reducing SARS-CoV-2 NVL. Additives to saline may have a clinical benefit, but further studies are needed to elucidate their isolated impacts on NVL. Data on PVP-I is inconclusive and further studies are warranted to determine the ideal concentration for irrigation. Laryngoscope, 2024.

Intranasal delivery of sulpiride nanostructured lipid carrier to central nervous system; in vitro characterization and in vivo study

The low and erratic oral absorption of sulpiride (SUL) a dopaminergic receptor antagonist, and its P-glycoprotein efflux in the gastrointestinal tract restricted its oral route for central nervous system disorders. An intranasal formulation was formulated based on nanostructured lipid carrier to tackle these obstacles and deliver SUL directly to the brain. Sulipride-loaded nanostructured lipid carrier (SUL-NLC) was prepared using compritol®888 ATO and different types of liquid lipids and emulsifiers. SUL-NLCs were characterized for their particle size, charge, and encapsulation efficiency. Morphology and compatibility with other NLC excipients were also studied. Moreover, SUL in vitro release, nanodispersion stability, in vivo performance and SUL pharmacokinetics were investigated. Results delineates that SUL-NLC have a particle size ranging from 366.2 ± 62.1 to 640.4 ± 50.2 nm and encapsulation efficiency of 75.5 ± 1.5%. SUL showed a sustained release pattern over 24 h and maintained its physical stability for three months. Intranasal SUL-NLC showed a significantly (p < 0.01) higher SUL brain concentration than that found in plasma after oral administration of commercial SUL product with 4.47-fold increase in the relative bioavailability. SUL-NLCs as a nose to brain approach is a promising formulation for enhancing the SUL bioavailability and efficient management of neurological disorders.