Quercetin loaded silver nanoparticles in hydrogel matrices for diabetic wound healing.

Quercetin (QCT) is an effective antioxidant, antifibrotic and wound healing agent. Silver nanoparticles (AgNPs) are an effective antimicrobial, antifungal and wound healing agent and considered as gold standard for wound treatment especially diabetic and burn wounds. The present study aimed to investigate QCT loaded AgNPs in hydrogel matrices (QCT-AgNPs hydrogel) as synergistic treatment paradigms for diabetic wound. Quality by Design approach was employed for the optimization of hydrogel preparation using carbopol-934 andaloevera.The developed QCT-AgNPs hydrogel was characterized for hydrodynamic diameter, %entrapment efficiency (%EE), surface morphology, texture analysis,in-vitrodrug release, skin irritation study,ex-vivopermeation study (confocal study), and antimicrobial efficacy. The optimized formulation showed hydrodynamic diameter of ∼44.1 nm with smooth spherical surface morphology and ∼92.09% of QCT was entrapped in QCT-AgNPs hydrogel matrices. The antimicrobial study revealed superior therapeutic efficacy of QCT-AgNPs hydrogel in comparison to marketed (MRKT) gel onS. aureusandE. coli. Moreover,in-vivoresults demonstrated that QCT-AgNPs hydrogel significantly (p < 0.001) reduced the wound gap and increased % re-epithelialization compared with diabetic control after 18 d of post treatment in excisional diabetic wound model. In conclusion, this study opens up an avenue for the treatment of diabetic wound.

Filgrastim loading in PLGA and SLN nanoparticulate system: a bioinformatics approach.

OBJECTIVE: In this research work, we hypothesized to predict the nanoparticulate system, best suited for targeted delivery of filgrastim. Significance: Targeted delivery of filgrastim to bone marrow is required to decrease the incidence of neutropenia/febrile neutropenia. This is achieved by nanoparticulate systems, duly designed by bioinformatics approach. METHOD: The targeted delivery of filgrastim in nanoparticulate system was achieved by molecular dynamics (MD) simulation studies. Two matrices comprising PLGA and SLN (tripalmitin, core component of SLN system) were modeled separately with proposed drug filgrastim. Energy minimization of all systems was done using the steepest descent method. PLGA and tripalmitin systems were equalized at 310 °C, at 1 bar pressure with Berendsen barostat for 200 ps using a v-rescale thermostat for 100 ps. Atomistic MD simulations of four model system and mass density of interacting systems were calculated. RESULTS: The mass density maps of each nanoparticle system, that is, PLGA and tripalmitin showed an increase in density toward the end of the simulation. The contact numbers attained equilibria with the average number of approx.. 1500 contacts in case of tripalmitin-filgrastim system. While PLGA-filgrastim system shows lesser contacts as compared to tripalmitin with average contacts of approx. 1000.The binding free energy was predicted to be -1104 kJ/mol in tripalmitin-filgrastim complex and -421 kJ/mol in PLGA-filgrastim system. CONCLUSION: Findings of study revealed that both nanoparticle systems assumed to be good model for drug-carrier systems. Though SLN systems were thought to be more appropriate than PLGA, still the in vivo findings could ascertain this hypothesis in futuristic work.

Enhancement in brain uptake of vitamin D3 nanoemulsion for treatment of cerebral ischemia: formulation, gamma scintigraphy and efficacy study in transient middle cerebral artery occlusion rat models.

AIM: For the treatment of cerebral ischaemia, vitamin-D3 loaded nanoemulsions were developed. METHOD: Tween 20 and polyethylene glycol were chosen as surfactant/co-surfactant, while oleic acid as the oil phase. The formulation was characterised for various in-vitro parameters. Targeting efficiency was investigated through radiometry, gamma scintigraphy and efficacy was studied in transient middle cerebral artery occlusion (MCAo) rat model. RESULT: Vitamin D3-nanoemulsion showed a mean size range of 49.29 ± 10.28 nm with polydispersity index 0.17 ± 0.04 and zeta potential 13.77 mV. The formulation was found stable during thermodynamic stability study and permeated within 180 min through sheep nasal mucosa (permeation coefficient 7.873 ± 0.884 cm/h). Gamma scintigraphy and radiometry assay confirmed better percentage deposition (2.53 ± 0.17%) of 99mTc-vitamin D3-nanoemulsion through nasal route compared to IV administered 99mTc-vitamin D3 solution (0.79 ± 0.03%). Magnetic Resonance Imaging (MRI) of the ischaemic model confirmed better efficacy of vitamin D3-nanoemulsion. CONCLUSION: This work demonstrated better permeation, deposition, and efficacy of vitaminD3-nanoemulsion through the intranasal route.

Decontamination of rat and human skin experimentally contaminated with 99mTc, 201Tl and 131I radionuclides using "Dermadecon" - a skin decontamination kit: an efficacy study.

Radioactive skin contamination is one of the most likely risks which occurs after accidental or occupational radiological accidents apart from internal contamination. In such cases where the radioactive contamination has occurred, the person who is contaminated should be decontaminated as early as possible to reduce the damaging health effects of radiation. In the present study, the decontamination efficiency of a developed skin decontamination kit "dermadecon" has been evaluated in animal models and human subjects using gamma scintigraphy. Decontamination efficiency (percentage of the radioactive contaminant removed) was calculated for each radioactive isotope of the study and compared with control where general washing procedure was followed using liquid and soap. The effectiveness of the kit was calculated in animal model with respect to 99mTc-sodium-pertechnetate (99mTcO4-), 201TlCl and 131I and was found 92.84 ± 4.9%, 91.18 ± 3.23% and 94.67 ± 2.92%, respectively. Whereas, in case of human skin, the decontamination efficiency for 99mTcO4- was observed to be 95.00 ± 3.21%. On the basis of findings from the study, it can be concluded that the decontamination agents of the used skin decontamination kit are effective for removal of localized radioactive contaminants from skin, as compared with normal decontamination using soap and water.

Development and Gamma Scintigraphy Study of Trigonella foenum-graecum (Fenugreek) Polysaccharide-Based Colon Tablet.

The major concern with the use of some synthetic excipients is their safety towards biological tissues, hence influencing the reliability of products. With the aim to minimize dependency on highly toxic synthetic excipients, the present study was designed to deliver metronidazole (MNZ) into the colonic region for localized treatment of amoebiasis using natural polysaccharide-based drug delivery. Compression-coated tablets were prepared using water extractable natural polysaccharide from Trigonella foenum-graecum (FG). Physical properties of the tablets were evaluated and dissolution study was performed at pH 1.2, 6.8, and 7.4 with rat cecal material. Results indicate that all batches demonstrated pH-dependent drug release and prevented release into the stomach, allowing traces into the intestine and highest availability into the colon. A significant correlation (r2 = 0.975) was found between the coating levels of extracted polysaccharide and lag time release of drug. Gamma scintigraphy images of in vivo study conducted on human volunteers showed a small intestinal transit time, i.e., 3-5 (4.2 ± 0.4) h and confirmed that the tablets reached the colon within 6-8 h. The present study revealed that the FG polysaccharide-based double compression tablets may be promising colon-specific drug carriers with reduced toxic effects of commonly used synthetic excipients.

Development and gamma scintigraphy evaluation of gastro retentive calcium ion-based oral formulation: an innovative approach for the management of gastro-esophageal reflux disease (GERD).

Calcium chloride is an essential calcium channel agonist which plays an important role in the contraction of muscles by triggering calcium channel. First time hypothesized about its role in the treatment of GER (gastro-esophageal reflux) and vomiting disorder due to its local action. There are two objectives covered in this study as first, the development and optimization of floating formulation of calcium chloride and another objective was to evaluate optimized formulation through gamma scintigraphy in human subjects. Gastro retentive formulation of calcium chloride was prepared by direct compression method. Thirteen tablet formulations were designed with the help of sodium chloride, HPMC-K4M, and carbopol-934 along with effervescing agent sodium bicarbonate and citric acid. Formulation (F8) fitted best for Korsmeyer-Peppas equation with an R2 value of 0.993. The optimized formulation was radiolabelled with 99mTc-99 m pertechnetate for its evaluation by gamma scintigraphy. Gastric retention (6 h) was evaluated by gamma scintigraphy in healthy human subjects and efficacy of present formulation confirmed in GER positive human subjects. Gamma scintigraphy results indicated its usefulness in order to manage GERD. Stability studies of the developed formulation were carried out as per ICH guidelines for region IV and found out to be stable for 24 months.

Reporting multitargeted potency of Tiaprofenic acid against lung cancer: Molecular fingerprinting, MD simulation, and MTT-based cell viability assay studies.

Lung Cancer (LC) is among the most death-causing cancers, has caused the most destruction and is a gender-neutral cancer, and WHO has kept this cancer on its priority list to find the cure. We have used high-throughput virtual screening, standard precision docking, and extra precise docking for extensive screening of Drug Bank compounds, and the uniqueness of this study is that it considers multiple protein targets of prognosis and metastasis of LC. The docking and MM\GBSA calculation scores for the Tiaprofenic acid (DB01600) against all ten proteins range from -8.422 to -5.727 kcal/mol and - 47.43 to -25.72 kcal/mol, respectively. Also, molecular fingerprinting helped us to understand the interaction pattern of Tiaprofenic acid among all the proteins. Further, we extended our analysis to the molecular dynamic simulation in a neutralised SPC water medium for 100 ns. We analysed the root mean square deviation, fluctuations, and simulative interactions among the protein, ligand, water molecules, and protein-ligand complexes. Most complexes have shown a deviation of <2 Å as cumulative understanding. Also, the fluctuations were lesser, and only a few residues showed the fluctuation with a huge web of interaction between the protein and ligand, providing an edge that supports that the protein and ligand complexes were stable. In the MTT-based Cell Viability Assay, Tiaprofenic Acid exhibited concentration-dependent anti-cancer efficacy against A549 lung cancer cells, significantly reducing viability at 100 µg/mL. These findings highlight its potential as a therapeutic candidate, urging further exploration into the underlying molecular mechanisms for lung cancer treatment.

Emerging global trends and development in forensic toxicology: A review.

This study conducts a comprehensive analysis of forensic toxicology research trends, publication patterns, author's contributions, and collaboration. Utilizing the Scopus database, we scrutinized 3259 articles across 348 journals spanning from 1975 to 2023. Analysis employed diverse software tools such as VOSviewer, RStudio, MS Excel, and MS Access to dissect various publication aspects. We observed a notable surge in publications post-2007, indicating heightened research interest. Leading contributors included the United States, Germany, and Italy, with Logan B.K. emerging as the most prolific author. Forensic Science International stood out as the primary journal, publishing 888 articles and accruing significant citations. Keyword co-occurrences such as "forensic toxicology," "forensic science," and "toxicology" underscored core thematic areas in the field. Moreover, extensive research collaboration, especially among Western nations in Europe, was evident. This study underscores the imperative for enhanced collaboration between developing and developed nations to foster further advancements in forensic science. Strengthened partnerships can catalyze innovation, facilitate knowledge dissemination, and address emerging challenges, thereby propelling the field of forensic toxicology toward new frontiers of discovery and application.

COVID-19 influenced gut dysbiosis, post-acute sequelae, immune regulation, and therapeutic regimens.

The novel coronavirus disease 2019 (COVID-19) pandemic outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has garnered unprecedented global attention. It caused over 2.47 million deaths through various syndromes such as acute respiratory distress, hypercoagulability, and multiple organ failure. The viral invasion proceeds through the ACE2 receptor, expressed in multiple cell types, and in some patients caused serious damage to tissues, organs, immune cells, and the microbes that colonize the gastrointestinal tract (GIT). Some patients who survived the SARS-CoV-2 infection have developed months of persistent long-COVID-19 symptoms or post-acute sequelae of COVID-19 (PASC). Diagnosis of these patients has revealed multiple biological effects, none of which are mutually exclusive. However, the severity of COVID-19 also depends on numerous comorbidities such as obesity, age, diabetes, and hypertension and care must be taken with respect to other multiple morbidities, such as host immunity. Gut microbiota in relation to SARS-CoV-2 immunopathology is considered to evolve COVID-19 progression via mechanisms of biochemical metabolism, exacerbation of inflammation, intestinal mucosal secretion, cytokine storm, and immunity regulation. Therefore, modulation of gut microbiome equilibrium through food supplements and probiotics remains a hot topic of current research and debate. In this review, we discuss the biological complications of the physio-pathological effects of COVID-19 infection, GIT immune response, and therapeutic pharmacological strategies. We also summarize the therapeutic targets of probiotics, their limitations, and the efficacy of preclinical and clinical drugs to effectively inhibit the spread of SARS-CoV-2.

Nanoparticles toxicity: an overview of its mechanism and plausible mitigation strategies.

Over the last decade, nanoparticles have found great interest among scientists and researchers working in various fields within the realm of biomedicine including drug delivery, gene delivery, diagnostics, targeted therapy and biomarker mapping. While their physical and chemical properties are impressive, there is growing concern about the toxicological potential of nanoparticles and possible adverse health effects as enhanced exposure of biological systems to nanoparticles may result in toxic effects leading to serious contraindications. Toxicity associated with nanoparticles (nanotoxicity) may include the undesired response of several physiological mechanisms including the distressing of cells by external and internal interaction with nanoparticles. However, comprehensive knowledge of nanotoxicity mechanisms and mitigation strategies may be useful to overcome the hazardous situation while treating diseases with therapeutic nanoparticles. With the same objectives, this review discusses various mechanisms of nanotoxicity and provides an overview of the current state of knowledge on the impact of nanotoxicity on biological control systems and organs including liver, brain, kidneys and lungs. An attempt also been made to present various approaches of scientific research and strategies that could be useful to overcome the effect of nanotoxicity during the development of nanoparticle-based systems including coating, doping, grafting, ligation and addition of antioxidants.

Retrospection of Seldom-Known Causes and Presentations of Partial Empty Sella Syndrome.

Pituitary gland shrinkage or flattening obscures it from view on an MRI, giving the impression that it is an empty sella. On the other hand, if some viable pituitary gland tissue is still seen on the MRI scan, a diagnosis of partial empty sella can be made. Diminished physiological and functional reserve in the elderly can result in a bad prognosis if not treated early. Therefore, there is a need to become familiar with fewer known causes and presentations of the empty sella or partial empty sella syndrome in older patients. We report a case of a 71-year-old female with multiple known ailments presenting with hypotension as the sole symptom. It urged us to investigate further and reach the root cause as partial empty sella syndrome with panhypopituitarism.

Illuminating Insights: Clinical Study Harnessing Pharmacoscintigraphy for Permeation Study of Radiolabeled Nimesulide Topical Formulation in Healthy Human Volunteers.

An alternative to oral administration for the delivery of therapeutic substances is the topical route, which frequently has comparable efficacy but may have a better tolerability profile. Gamma scintigraphy is a noninvasive technique that involves the application of radioactive substances to conduct biodistribution studies of therapeutic substances delivered through various routes. Nimesulide (NSD) was radiolabeled with technetium pertechnetate (Technetium99m [99mTc]) and this radiolabeled drug complex (99mTc-NSD) was used to prepare a topical gel formulation. The permeation of the radiolabeled drug from the topical gel was determined by gamma scintigraphy on human volunteers. The region of interest was calculated for the quantification of permeated radiolabeled drugs. This was observed that the mean percentage permeation of 99mTc-NSD was found to be 0.32 ± 0.22 to 36.37 ± 2.86 at 5 and 240 min. It was demonstrated that gamma scintigraphy may be a noninvasive and reliable technique for the determination of drug permeation through topical routes.

A calcium and zinc composite alginate hydrogel for pre-hospital hemostasis and wound care.

We developed, characterized, and examined the hemostatic potential of sodium alginate-based Ca2+ and Zn2+ composite hydrogel (SA-CZ). SA-CZ hydrogel showed substantial in-vitro efficacy, as observed by the significant reduction in coagulation time with better blood coagulation index (BCI) and no evident hemolysis in human blood. SA-CZ significantly reduced bleeding time (≈60 %) and mean blood loss (≈65 %) in the tail bleeding and liver incision in the mice hemorrhage model (p ≤ 0.001). SA-CZ also showed enhanced cellular migration (1.58-fold) in-vitro and improved wound closure (≈70 %) as compared with betadine (≈38 %) and saline (≈34 %) at the 7th-day post-wound creation in-vivo (p < 0.005). Subcutaneous implantation and intra-venous gamma-scintigraphy of hydrogel revealed ample body clearance and non-considerable accumulation in any vital organ, proving its non-thromboembolic nature. Overall, SA-CZ showed good biocompatibility along with efficient hemostasis and wound healing qualities, making it suitable as a safe and effective aid for bleeding wounds.

Green synthesis of ginger-encapsulated zinc oxide nanoparticles: Unveiling their characterization and selective cytotoxicity on MDA-MB 231 breast cancer cells.

Zinc oxide nanoparticles (ZnO-NPs) were synthesized using ginger (Zingiber officinale) extracts in a green synthesis approach and evaluated their in vitro cytotoxicity effect on the MDA-MB 231 breast cancer cell line. The bottom-up approach was employed to develop the green-synthesized ginger-encapsulated ZnO-NPs (GZnO-NPs) without using hazardous substances. The most substantial Fourier-transform infrared absorption peak of the ginger root extract was seen at 1634.24 cm-1. The peak also confirmed the presence of ginger root extract-encapsulated ZnO-NPs at 1556.79, 1471.54, and 1019.83 cm-1. It indicates that the biomolecules found in plant extracts behave as capping agents, aiding in the formation of nanoparticles. The mean particle sizes (PSs) of optimized GZnO-NPs of the ratios 1:2 were found to be 104.01 ± 7.12 nm with a zeta potential of -11.5 ± 1.31 mV. The X-ray diffraction and scanning electron microscope analysis confirmed that the prepared nanoparticles were spherical and crystalline, with PS ranging from 100 to 150 nm. The GZnO-NPs were subjected to MTT assay and cellular migration potential, and it was found that the inhibitory concentration on the MDA-MB 231 (breast) cancer cell line and scratch area showed a dose-dependent efficacy. The successfully green-synthesized GZnO-NPs effectively induced cell death in the MDA-MB 231 cancer cell line. The scratch assay results confirmed that prepared GZnO-NPs inhibited the proliferation and migration of cancerous cells.

A Case of Amoebic Liver Abscess Presenting as a Therapeutic Conundrum Necessitating the Exploration of Other Under-the-Radar Treatment Modalities.

Tropical countries have recorded incidences of amoebic liver abscess (ALA) owing to the more significant epidemiology and pathogenicity of the intestinal protozoan Entamoeba histolytica in these regions. However, the rise in the number of immigrants from such areas to developed countries has made it necessary to thoroughly review the diseases caused by the parasite globally. Patients generally present with the usual features of right upper quadrant pain, painful hepatomegaly, mild jaundice, and vomiting, to name a few; however, the condition can manifest varied presentations accompanied by a plethora of findings non-responsive to the standard treatment. Therefore, newer modalities should be considered by weighing their risks and benefits to reduce morbidity and mortality and improve patient outcomes.

Protective Effect of Organ Preservation Fluid Supplemented With Nicorandil and Rutin Trihydrate: A Comparative Study in a Rat Model of Renal Ischemia.

OBJECTIVES: The objective of organ preservation is sustained viability of detached/removed/isolated organs and subsequent successful posttransplant outcomes. Nicorandil (an ATP-sensitive potassium channel opener) is an efficacious agent to preserve lungs and heart. Rutin trihydrate (an antioxidant) inhibits free radical-mediated cytotoxicity and lipid peroxidation. We aimed to evaluate the efficacy of nicorandil and rutin trihydrate to enhance kidney preservation. MATERIALS AND METHODS: We prepared 2 versions of organ preservation fluid, supplemented with either nicorandil or rutin trihydrate, and used 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assays to evaluate the efficacy of these solutions in vitro (HEK293 human embryonic kidney cells), according to various cellular parameters such as ATP levels, reactive oxygen species, and cell viability. We also investigated the in vivo preservation efficacy in a rat model of renal ischemia and evaluated the immunohistological expression of apoptotic markers (caspase 3) in preserved rat kidney. RESULTS: We observed significant improvement of intracellular ATP levels (32 999 ± 1454 pmol/cell, n = 3; P < .05) in cells preserved in the nicorandil- supplemented solution compared with Custodiol solution (23 216 ± 1315 pmol/cell). Reactive oxygen species declined 1.25-fold (P < .05) in the presence of rutin trihydrate. Cell viability assays revealed a 4.8-fold increase in viability of renal cells preserved in the solutions supplemented with nicorandil or rutin trihydrate after 24-hour incubation compared with controls. In vivo, there were significant effects on serum creatinine (0.5480 ± 0.052, 0.956 ± 0.043 mg/dL) and blood urea nitrogen (85.36 ± 4.64, 92.85 ± 3.15 mg/dL) with the nicorandil and rutin trihydrate solutions, respectively. We observed suppressed expression of the apoptotic marker caspase 3 in groups treated with the 2 supplemented preservation fluids. CONCLUSIONS: Our results showed that solutions of organ preservation fluid supplemented with either nicorandil or rutin trihydrate can ameliorate cellular problems/dysfunction and facilitate sustained impro - vement of tissue survival and subsequent organ viability.

Evaluation of Decontamination Efficacy of Electrolytically Generated Hypochlorous Acid for the Vesicating Agent: A Multimodel Study.

BACKGROUND: Sulfur Mustard is a strong vesicant and chemical warfare agent that imposes toxicity to the lungs, eyes, and skin after accidental or intended exposure. OBJECTIVES: The current study was intended to explore in vitro and in vivo decontamination properties of electrolytically generated HOCl (hypochlorous acid) against CEES (2-chloroethyle ethyle sulphide), a known sulfur mustard simulant & vesicating agent. METHODS: in vitro studies were carried out using UV spectroscopy and GC-MS methods. In vivo studies were performed in Strain A and immune-compromised mice by subcutaneous as well as prophylactic topical administration of HOCl pretreated CEES. The blister formation and mortality were considered as end-point. Histopathological study was conducted on skin samples by H & E method. DNA damage studies measuring γ-H2AX and ATM have been carried out in human blood using flow cytometry. Anti-bacterial action was tested by employing broth micro dilution methods. A comparative study was also carried out with known oxidizing agents. RESULTS: The topical application of pre-treated CEES at 5, 30 min and 1 h time points showed significant (p<0.001) inhibition of blister formation. DNA damage study showed reduced mean fluorescence intensity of DSBs nearly 17-20 times, suggesting that HOCl plays a protective role against DNA damage. Histopathology showed no sign of necrosis in the epidermis upto 5 min although moderate changes were observed at 30 min. Pretreated samples were analyzed for detection of reaction products with m/z value of 75.04, 69.08, 83.93, 85.95, 123.99, 126.00, and 108.97. HOCl showed a strong bactericidal effect at 40 ppm. The absorbance spectra of HOCl treated CEES showed lowered peaks in comparison to CEES alone and other oxidizing agents. CONCLUSION: In a nutshell, our results signify the decontamination role of HOCl for biological surface application.

In vivo-wound healing studies of sodium thiosulfate gel in rats.

Sodium Thiosulfate (STS) is already reported as an antioxidant, anti-inflammatory agent with antiseptic, antifungal properties. The search for an ideal antiseptic still continues, which is lethal to all types of bacteria and their spores and sustain the activity for a longer time without any harm to the host tissue. The aim of the present study is to evaluate the effect of STS on curing of wounds in rats when compared to Betadine. We developed topical gels having 6% and 12% STS. The effects of STS on wound healing rate of Rats were evaluated against Betadine as positive control. Wounds of control group, selected as Group 1 was treated with normal saline (0.2 ml), twice a day. Reference standard control, designated as Group 2 rats were given with 0.2 ml Betadine twice a day. Rats in Groups 3 and 4 were treated with 0.2 ml of STS gel (6% or 12% respectively) twice a day. In our study, STS formulation has proved to be a safe and efficient wound healing product. It has a neutral pH and longer half life (>12 months). Higher STS dose of 12% proved to have a wound curing rate equivalent to that of Betadine. On 11th Day, 97 ± 0.79% healing was achieved with Betadine and 98 ± 0.67% with 12% STS Gel (∗P < 0.05). Microscopic images of H&E stained skin tissue from animals treated with Betadine and 12% STS formulation showed a reduction in scar size, lesser amount of inflammatory cells, higher fibroblasts and blood vessels, with considerable collagen accumulation. Furthermore, a significant enhancement in the levels of GPx, CAT and SOD was observed in the tissue at the wound site of the treated group. The IL 10 levels in both groups of STS-treated rats was increased, whereas, TNF-α levels were reduced significantly in tissue homogenate compared with control. Thus, this study shows the wound-healing performance of STS formulation. Further studies are necessary to understand the real mechanism of how STS formulation heals wounds.

Intranasal solid lipid nanoparticles for management of pain: A full factorial design approach, characterization & Gamma Scintigraphy.

Pain is a noxious stimulus caused due to tissue damage and varies from mild to severe. Nalbuphine (NLB) is an approved, inexpensive, non-controlled, opioid agonist/antagonist analgesic used worldwide in various clinical settings for pain management. The current study aims to formulate NLB loaded solid lipid nanoparticles (SLNs) using solvent injection technology. The morphological and chemical structure of the developed SLNs were characterized using Field Emission Scanning Electron Microscopy (FESEM), Transmission Electron Microscopy (TEM) and Fourier Transformation Infrared Spectroscopy (FTIR). The results revealed from the point prediction confirmation in design expert software was the formulation of NLB-SLNs with an average particle size of (170.07 ± 25.1 nm), encapsulation efficiency (93.6 ± 1.5%) & loading capacity of 26.67%. The in-vitro permeation of developed NLB-SLNs was observed to be 94.18% at 8 h when compared with NLB solution whose maximum permeation was seen within 3 h of application. Efficacy of the formulation was also evaluated using eddy's hot plate method, where the onset of action started within 10 min of administration, and the maximum effect was observed at 1 h. The NLB-SLNs was screened for cytotoxicity in human embryonic kidney cells (HEK-293), and the dosage was considered safe when administered intranasally in animal since no detectable effect to the brain was observed. Biodistribution and gamma scintigraphy study of NLB-SLNs showed the prepared formulation reaching the target site, i.e. brain and was retained. Conclusively, the prepared NLB-SLNs formulation was safe and effective in producing an analgesic effect in vivo.

Intranasal delivery of Naloxone-loaded solid lipid nanoparticles as a promising simple and non-invasive approach for the management of opioid overdose.

Naloxone is an opioid receptor antagonist that can eradicate all pre-indications of the toxicity and inverse the opioid overdose. However, oral administration of naloxone offers limitations such as its extensive first-pass metabolism that results in poor therapeutic effects. In order to resolve this issue, we developed intranasal solid-lipid nanoparticles in which naloxone was incorporated for the higher brain disposition of naloxone with superior therapeutic effects for the reversal of toxicity of opioid overdose. The preparation of naloxone loaded solid-lipid nanoparticles was done by employing the solvent evaporation method. Later, the designed formulation was optimized by Quality by Design approach, specifically, Box-Behnken method. The composition of optimized formulation was Glyceryl monostearate as a solid lipid (40 mg), Pluronic127 (0.5%) and Tween 80 (0.1%) as a surfactant and co-surfactant, respectively. Furthermore, the characterization of optimized formulation was achieved in terms of particle size, PDI, zeta potential, entrapment efficiency, and drug loading which were 190.2 nm, 0.082, -16 mV, 95 ± 0.532% and 19.08 ± 0.106%, respectively. Afterwards, in vitro, ex vivo and in vivo experiments were performed in which higher drug release and superior drug uptake by nasal membrane were observed for naloxone-loaded solid-lipid nanoparticles, later it was confirmed by confocal microscopy of ex vivo nasal membrane tissue. The findings of gamma scintigraphy investigation exhibited better deposition of naloxone-loaded solid-lipid nanoparticles as compared to naloxone solution. Also, the better deposition of naloxone by gamma scintigraphy was further validated by the investigation through the biodistribution study. Additionally, the key findings of the pharmacokinetic study revealed Cmax, Tmax, AUC0-t, AUC0-∞, T1/2 and Ke was found to be 163.95 ± 2.64 ng/ml, 240 ± 2.1 min, 17.75 ± 1.08 ng.hr/ml, 18.82 ± 2.51 ng.hr/ml, 70.71 ± 0.115 min, 0.098 ± 0.01 h-1 respectively. Lastly, investigations such as weight variation and histopathological proved the plausible potential of naloxone-loaded solid-lipid nanoparticles in terms of safety as no toxicity was noticed even after the administration of the three-folds dose of the normal dose. Therefore, considering all these findings, it could be easy to say that these developed naloxone-loaded solid-lipid nanoparticles could be administrated via intranasal route and can act as successful novel nanoformulation for the effective treatment of opioid overdose.