Association of cholesterol with hepatorenal markers and quality of life in diabetic patients before and after magnesium and potassium supplements.

Background: Magnesium and potassium are two critical minerals that have been linked to the treatment of diabetes and its consequences. A lack of magnesium has been linked to insulin resistance and diabetes, whereas potassium has been found to promote insulin sensitivity and glucose metabolism. The study aimed to determine the relationship between cholesterol, liver and kidney markers, and quality of life in diabetic patients before and after magnesium and potassium supplementation. Methods: It was a single-blind randomized controlled study at Lahore Garrison University and Lahore Medical Research Centre (LMRC). The study included 200 diabetes participants. Four groups were made based on supplements. Blood samples of all diabetes patients were obtained to assess their quality of life before and after using Mg + and K + supplements, as well as the association between cholesterol, liver, and kidney markers. Results: The participants' average age was 51.0 ± 11.08. 139 (69.5 %) of the 200 participants were female, whereas 26 (30.5 %) were male. There was no correlation between the quality of life measure and the patients' cholesterol levels before and after the magnesium and potassium supplementation. Furthermore, the kidney and liver indicators were not dependent on the diabetes individuals' cholesterol levels. Conclusions: The study concluded that none of the four groups noticed a significant effect of magnesium and potassium therapies on the patient's quality of life or cholesterol levels. However, more research is needed to determine if liver and kidney problems are linked to cholesterol levels before and after medication, as the current study found no significant correlation between the two parameters.

A Canadian single institution real-world experience using the CROSS trial regimen in the treatment of oesophageal and gastroesophageal junction carcinoma.

BACKGROUND: Trimodality therapy using the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial protocol is an accepted standard of care for locally advanced oesophageal and gastroesophageal junction cancers. For medically inoperable patients, chemoradiotherapy (CRT) has been a therapeutic option. AIMS: This single institution review aimed to assess the real-world application of the CROSS trial protocol. METHODS: This is a retrospective review of 83 patients who underwent CRT with carboplatin and paclitaxel with trimodality or definitive intent between June 2012 and June 2018. Sixty-five patients underwent neoadjuvant CRT (NCRT); 40 had surgery, 18 had definitive CRT (DCRT). Patients' demographics, clinical, pathological, treatment and surgical characteristics were assessed. The data were analysed in exploratory analyses and Kaplan-Meier curves. RESULTS: For 83 patients, the following median values were seen: radiotherapy dose, 50.4 Gy; chemotherapy doses, 5; and time from CRT to surgery, 62 days. Twenty-three percent NCRT and 72% DCRT patients were aged ≥75 years, and 49% and 33% of these respectively had no interruptions to CRT. Patients aged ≥75 years were more likely to have DCRT (P = 0.001). Patients who underwent surgery were younger (P = 0.04). For NCRT and surgery, NCRT only and DCRT respectively, median overall survival was 35.5, 12.1 and 17.1 months (log rank P = 0.008); progression-free survival was 32.2, 10 and 9.6 months (log rank P = 0.001). CONCLUSIONS: Despite broadening of the CROSS trial eligibility criteria in our real-world data, there appears to be a survival benefit with trimodality therapy. The use of carboplatin and paclitaxel in DCRT may be of value and requires further study.

Surfactant free synthesis of cationic nano-vesicles: A safe triple drug loaded vehicle for the topical treatment of cutaneous leishmaniasis.

The basic aim of the study was to develop and evaluate the triple drug loaded cationic nano-vesicles (cNVs), where miltefosine was used as a replacement of surfactant (apart from its anti-leishmanial role), in addition to meglumine antimoniate (MAM) and imiquimod (Imq), as a combination therapy for the topical treatment of cutaneous leishmaniasis (CL). The optimized formulation was nano-sized (86.2 ±â€¯2.7 nm) with high entrapment efficiency (63.8 ±â€¯2.1% (MAM) and 81.4 ±â€¯2.3% (Imq)). In-vivo skin irritation assay showed reduced irritation potential and a decrease in the cytotoxicity of cNVs as compared to conventional NVs (having sodium deoxycholate as a surfactant). A synergistic interaction between drugs was observed against intracellular amastigotes, whereas the in-vivo antileishmanial study presented a significant reduction in the parasitic burden. The results suggested the potential of surfactant free, triple drug loaded cNVs as an efficient vehicle for the safe topical treatment of CL.

7ß-(3-Ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z Notonipetranone Attenuates Neuropathic Pain by Suppressing Oxidative Stress, Inflammatory and Pro-Apoptotic Protein Expressions.

7ß-(3-Ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a sesquiterpenoid obtained from a natural source has proved to be effective in minimizing various side effects associated with opioids and nonsteroidal anti-inflammatory drugs. The current study focused on investigating the effects of ECN on neuropathic pain induced by partial sciatic nerve ligation (PSNL) by mainly focusing on oxidative stress, inflammatory and apoptotic proteins expression in mice. ECN (1 and 10 mg/kg, i.p.), was administered once daily for 11 days, starting from the third day after surgery. ECN post-treatment was found to reduce hyperalgesia and allodynia in a dose-dependent manner. ECN remarkably reversed the histopathological abnormalities associated with oxidative stress, apoptosis and inflammation. Furthermore, ECN prevented the suppression of antioxidants (glutathione, glutathione-S-transferase, catalase, superoxide dismutase, NF-E2-related factor-2 (Nrf2), hemeoxygenase-1 and NAD(P)H: quinone oxidoreductase) by PSNL. Moreover, pro-inflammatory cytokines (tumor necrotic factor-alpha, interleukin 1 beta, interleukin 6, cyclooxygenase-2 and inducible nitric oxide synthase) expression was reduced by ECN administration. Treatment with ECN was successful in reducing the caspase-3 level consistent with the observed modulation of pro-apoptotic proteins. Additionally, ECN showed a protective effect on the lipid content of myelin sheath as evident from FTIR spectroscopy which showed the shift of lipid component bands to higher values. Thus, the anti-neuropathic potential of ECN might be due to the inhibition of oxidative stress, inflammatory mediators and pro-apoptotic proteins.

Antinociceptive properties of 25-methoxy hispidol A, a triterpinoid isolated from Poncirus trifoliata (Rutaceae) through inhibition of NF-κB signalling in mice.

The 25-methoxy hispidol A (25-MHA) is a triterpenoid, isolated from the immature fruit of Poncirus trifoliata (Rutaceae). The pretreatment with 25-MHA markedly (p < 0.001) attenuated the formalin-induced biphasic responses as well as acetic acid-induced writhing responses. The intraperitoneal administration of 25-MHA significantly attenuated the mechanical hyperalgesia (p < 0.001) and allodynia (p < 0.05). Similarly, 25-MHA also significantly attenuated (p < 0.001) complete Freund's adjuvant (CFA)-induced paw edema in mice. The 25-MHA treatment significantly attenuated the production of nuclear kappa B (NF-κB) (p65 nuclear subunit). The cytokines are the important mediators of inflammation and pain; however, treatment with 25-MHA exhibited significant inhibition (p < 0.001) on the mRNA expression levels of various inflammatory mediators. The 25-MHA administration also significantly enhanced antioxidant enzymes (p < 0.001) and inhibited the oxidative stress markers. The current study indicates that 25-MHA significantly (p < 0.001) inhibited the nitric oxide (NO) in mice plasma. Similarly, the haematoxylin and eosin (H&E) staining shows that 25-MHA administration significantly inhibited the inflammatory process in the mice paw tissue compared with the CFA-treated group. The 25-MHA treatment did not exhibited any toxicity on the liver, kidney, muscles strength, and motor co-ordination in mice. The 25-MHA was coadministered with the various drugs such as tramadol, piroxicam, and gabapentin to observe the synergistic effect.

Biaryl scaffold-focused virtual screening for anti-aggregatory and neuroprotective effects in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a primary cause of dementia in ageing population affecting more than 35 million people around the globe. It is a chronic neurodegenerative disease caused by defected folding and aggregation of amyloid beta (Aß) protein. Aß is formed by the cleavage of membrane embedded amyloid precursor protein (APP) by using enzyme 'transmembrane aspartyl protease, ß-secretase'. Inhibition of ß-secretase is a viable strategy to prevent neurotoxicity in AD. Another strategy in the treatment of AD is inhibition of acetylcholinesterase. This inhibition reduces the degradation of acetylcholine and temporarily restores the cholinergic function of neurons and improves cognitive function. Monoamine oxidase and higher glutamate levels are also found to be linked with Aß peptide related oxidative stress. Oxidative stress leads to reduced activity of glutamate synthase resulting in significantly higher level of glutamate in brain. The aim of this study is to perform in silico screening of a virtual library of biaryl scaffold containing compounds potentially used for the treatment of AD. Screening was done against the primary targets of AD therapeutics, acetylcholinesterase, ß-secretase (BACE1), Monoamine oxidases (MAO) and N-Methyl-D-aspartate (NMDA) receptor. Compounds were screened for their inhibitory potential by employing molecular docking approach using AutoDock vina. Binding energy scores were embodied in the heatmap to display varies strengths of interactions of the ligands targeting AD. RESULTS: Several ligands showed notable interaction with at least two targets, but the strong interaction with all the targets is shown by very few ligands. The pharmacokinetics of the interacting ligands was also predicted. The interacting ligands have good drug-likeness and brain availability essential for drugs with intracranial targets. CONCLUSION: These results suggest that biaryl scaffold may be pliable to drug development for neuroprotection in AD and that the synthesis of further analogues to optimize these properties should be considered.

Correction to: Anti-inflammatory, anti-rheumatic and analgesic activities of 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-N-propylbenzenesulphonamide (MOPBS) in rodents.

Unfortunately, Fig. 1 was incorrectly published in the original publication. The corrected Fig. 1 is given as below.

Anti-inflammatory, anti-rheumatic and analgesic activities of 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-N-propylbenzenesulphonamide (MOPBS) in rodents.

Chronic inflammation is pathologically associated with various clinical conditions such as rheumatoid arthritis. Several anti-inflammatory and analgesic drugs currently available in market presents a wide range of problems. Therefore, the current study was aimed to evaluate anti-inflammatory and analgesic activities of newly synthesized compound 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-N-propylbenzenesulphonamide (MOPBS). Carrageenan and CFA-induced models were developed for evaluation of anti-inflammatory and analgesic activity. Quantitative real-time PCR (qRT-PCR) was performed to determine the mRNA expression levels of inflammatory mediators. Pain behaviours were evaluated by performing Von Frey, Randall Selitto, cold acetone and hot plate test respectively. X-ray imaging and haematoxylin and eosin (H&E) staining were performed for examination of soft tissues of treated mice paw. Additionally, Kodzeila's screen test and weight test were performed for determination of any side effects on motor function and muscle strength. Acute pretreatment of animals with MOPBS (1, 10, 50 and 100 mg/kg, i.p.) produced a significant reduction of paw oedema against carrageenan-induced acute inflammation as well as notable inhibition of mechanical hyperalgesia, allodynia and thermal hyperalgesia. Similarly, in chronic inflammation model, administration of MOPBS (50 mg/kg, i.p.) produced a remarkable reduction of paw oedema. Additionally, MOPBS pretreatment showed a significant inhibition of thermal hyperalgesia, mechanical allodynia, and mechanical hyperalgesia in chronic arthritis model. Several pro-inflammatory mediators such as nitric oxide (NO), vascular endothelial growth factor (VEGF), interleukins (IL-1ß, IL-6) and tumor necrosis factor-α (TNF-α) were inhibited by MOPBS treatment in blood plasma and paw tissues, respectively. MOPBS also enhanced the mRNA expression levels of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), superoxide dismutase (SOD2) and heme oxygenase (HO-1) and in turn reduced arthritis severity and inflammation. Furthermore, anti-inflammatory data were confirmed by X-rays and histological analysis. MOPBS pretreatment did not produce any apparent toxic effect on gastric, kidney and liver function and on muscle strength and motor function. Hence, the present data suggest that MOPBS might be a candidate for several chronic inflammatory diseases such RA and other auto-immune diseases.

COVID-19 outbreak: Impact on global economy.

COVID-19 has been considered the most significant threat since World War II and the greatest global health disaster of the century. Wuhan City, Hubei Province, China, reported a new infection affecting residents in December 2019. The Coronavirus Disease 2019 (COVID-19) has been named by the World Health Organization (WHO). Across the globe, it is spreading rapidly, posing significant health, economic, and social challenges for everyone. The content of this paper is solely intended to provide a visual overview of COVID-19 global economic impact. The Coronavirus outbreak is causing a global economic collapse. Most countries have implemented full or partial lockdown measures to slow the spread of disease. The lockdown has slowed global economic activity substantially, many companies have reduced operations or closed down, and people are losing their jobs at an increasing rate. Service providers are also affected, in addition to manufacturers, agriculture, the food industry, a decline in education, the sports industry, and of entertainment sector also observed. The world trade situation is expected to deteriorate substantially this year.

Triple-combination therapy for cutaneous leishmaniasis using detergent-free, hyaluronate-coated elastic nanovesicles.

Aim: To develop and evaluate detergent-free, triple-drug-loaded, hyaluronate-coated elastic nanovesicles (H-ENVs) for the topical treatment of cutaneous leishmaniasis. Materials & methods: H-ENVs were developed and evaluated for vesicle size, entrapment efficiency, skin permeation and antileishmanial potential. Results: A 15.7 and 28.6% decrease in the cytotoxicity of paromomycin and amphotericin B, respectively, was observed in detergent-free ENVs compared with conventional ENVs. H-ENVs improved the efficacy of paromomycin against promastigote and amastigote models of leishmaniasis by 4- and 7.5-fold, respectively. In vivo investigation of H-ENVs demonstrated efficient topical management of cutaneous leishmaniasis. Conclusion: The results indicate the potential of H-ENVs as a safe topical treatment choice for cutaneous leishmaniasis.

Application of topical gel is an attractive alternative to oral or intravenous administration of drugs and is likely to deliver a higher dose of the drug to the target site with only rare systemic adverse effects. Nanotechnology-based topical drug delivery is an attractive aspect of pharmaceutical sciences that expresses interest in the topical treatment of cutaneous leishmaniasis. The authors' research focuses on the development and evaluation of novel multidrug-loaded, detergent-free nanovesicles for the simple and effective topical treatment of cutaneous leishmaniasis.

Unlocking the Effect of Supervisor Incivility on Work Withdrawal Behavior: Conservation of Resource Perspective.

Workplace incivility has gotten a lot of attention in recent decades. Researchers have looked at many forms of aggressive conduct in the workplace and their negative impacts on individuals and businesses. The goal of this study was to see how incivility among supervisors leads to work withdrawal and when this link might be mitigated. We argued that supervisor incivility indirectly influences work withdrawal behavior through job insecurity, and that emotional intelligence moderates this connection. This study attempted to evaluate the influence of supervisor incivility on the job withdrawal behavior of personnel working in several banks Lahore by drawing on affective events theory and conservation of resource theory. Data were gathered from 350 workers of banks in Lahore, Gujranwala, and Sheikhupura to test our assumptions, and SPSS 24 was used to generate and analyze data with Hayes Process. The findings revealed a strong link between supervisor incivility and job insecurity but no link between supervisor incivility and work withdrawal behavior. The idea of moderation was validated, since emotional intelligence moderates the relationship between job insecurity and job withdrawal behavior. There are also suggestions for more empirical studies and theoretical and practical ramifications.

Palyno-morphological attributes of some selected plant species of family Asteraceae from district Dera Ismail Khan, KPK, Pakistan.

The current study aimed to investigate the palyno-morphological features of Asteraceous species from District Dera Ismail Khan, Khyber Pakhtunkhwa, Pakistan. A total of 13 species were collected, pressed, identified, and examined by using light and scanning electron microscopy. Both qualitative and quantitative pollen characters were observed, that is, equatorial and polar diameter, number of pores and colpi, exine thickness, exine sculpturing, pollen shape, and P/E ratio. Pollen shapes observed in studied taxa were spheroidal, suboblate, oblate-spheroidal, and lophate-spheroidal. The aperturation patterns of pollens vary from tricolporate to tetracolporate. The maximum polar and equatorial diameter of 75-100 (87.5 ± 13.6) µm and 87.5-117.5 (102.5 ± 16.4) µm, respectively, was recorded in Echinops echinatus, while minimum polar and equatorial diameter of 20-22.5 (21 ± 1.36) µm and 22.5-25 (23.5 ± 1.36) µm, respectively, was recorded in Aster subulatus. Six types of exine sculpturing patterns were observed; echinate, micro-echinate, echinate-microreticulate, microreticulate, echinate-perforate, and scabrate. Maximum exine thickness of 8.75 µm was recorded in E. echinatus and minimum of 1.25 µm in Launaea mucronata. The pollen morphology has valuable significance in understanding the taxonomy of different plant groups and plays a central role in the correct identification and classification of Asteraceous flora at species, generic, and tribe levels.

Safety of Immunotherapy Rechallenge After Immune-related Adverse Events in Patients With Advanced Cancer.

This retrospective study aimed to investigate the safety profile of continuing or rechallenging patients with advanced cancer who developed grade≥2 immune-related adverse events (irAEs) on immunotherapy-based regimens. Our study had 25, 20, and 40 patients (N=85) in the Treatment Continuation (TCG), Non-Rechallenge (NRG), and Rechallenge Groups (RG), respectively. Subsequent irAEs recurrence were more common in RG than TCG and NRG (78% vs. 56% vs. 25%, P<0.001). The same subsequent irAEs recurrences occurred on 42% of RG, 4% of TCG, and 15% of NRG (P<0.001). On the RG, there was a nonstatistical trend of shortening interval time between time from treatment rechallenge to subsequent irAEs when compared with time from first treatment to initial grade≥2 irAEs (5.86 vs. 8.86 wk, P=0.114). Patients who had cardiac irAEs were not rechallenged. Several high-risk features were identified to prognosticate risk of irAEs recurrences upon treatment rechallenge, including age 65 years and above (P=0.007), programmed cell death protein 1 inhibitors (P<0.001), grade 3 irAEs (P=0.003), pneumonitis type (P=0.048), any systemic corticosteroid use (P=0.001)/high-dose systemic corticosteroid use (P=0.007)/prolonged ≥4-week corticosteroid use (P=0.001) for irAEs management, and early development of irAEs (P=0.003). Our study concluded that it was relatively safe to continue or rechallenge patients with advanced cancers on immunotherapy-based regimens postdevelopment of certain grade≥2 irAEs, except for cardiac, neurological, or any grade 4 irAEs. Subsequent irAEs were common, no more severe, involved the same organ sites, and occurred more quickly than the original irAE. Close monitoring of all potential irAEs is required when rechallenging a patient on immunotherapy, especially for patients with high-risk features.

Prognostic Significance of Substance P/Neurokinin 1 Receptor and Its Association with Hormonal Receptors in Breast Carcinoma.

Expression and immunolocalization of Substance P (SP)/Neurokinin-1 Receptor (NK-1R) in breast carcinoma (BC) patients and its association with routine proliferative markers (ER, PR, HER2/neu, and Ki-67) were evaluated. A cross-sectional study was performed on 34 cases of BC. There were 23 cases of group A (grade III), 8 of group B (grade II), and only 3 cases of group C (grade I). All samples were then processed for SP and NK-1R immunohistochemistry for few cases. 14/23 cases (61%) of group A, 7/8 cases (88%) of group B, and 2/3 (67%) cases of group C were SP positive. Overall, strong staining (≥10% tumor cells), labeled as "+3," was observed in 9/14 (64.2%) cases of group A and 1/8 (12.5%) cases of group B. Moderate staining labelled as "+2" (in ≥10% tumor cells) was observed in 3/14 (21.4%) cases of group A and 4/8 (50%) cases of group B. Weak positive staining "+1" was observed in only 2/14 (14.28%) cases of group A, 2/8 (25%) cases of group B, and all 2/2 (100%) cases of group C. SP and NK-1R are overexpressed in breast carcinomas, and there is significant association between the grade of tumor and their overexpression.

Comprehensive Analysis of Genes Associated With Sudden Infant Death Syndrome.

Background: Sudden infant death syndrome (SIDS) is a tragic incident which remains a mystery even after post-mortem investigation and thorough researches. Methods: This comprehensive review is based on the genes reported in the molecular autopsy studies conducted on SIDS so far. A total of 20 original studies and 7 case reports were identified and included in this analysis. The genes identified in children or adults were not included. Most of the genes reported in these studies belonged to cardiac channel and cardiomyopathy. Cardiac channel genes in SIDS were scrutinized for further analysis. Results: After screening and removing the duplicates, 42 unique genes were extracted. When the location of these genes was assessed, it was observed that most of these belonged to Chromosomes 11, 1 and 3 in sequential manner. The pathway analysis shows that these genes are involved in the regulation of heart rate, action potential, cardiac muscle cell contraction and heart contraction. The protein-protein interaction network was also very big and highly interactive. SCN5A, CAV3, ALG10B, AKAP9 and many more were mainly found in these cases and were regulated by many transcription factors such as MYOG C2C1 and CBX3 HCT11. Micro RNA, "hsa-miR-133a-3p" was found to be prevalent in the targeted genes. Conclusions: Molecular and computational approaches are a step forward toward exploration of these sad demises. It is so far a new arena but seems promising to dig out the genetic cause of SIDS in the years to come.

Vascular endothelial growth factor attenuates status epilepticus-induced behavioral impairments in rats.

Vascular endothelial growth factor (VEGF) is a vascular growth factor more recently recognized as a neurotrophic factor (for review, see Storkebaum E, Lambrechts D, Carmeliet P. BioEssays 2004;26:943-54). We previously reported that endogenous VEGF protein is dramatically upregulated after pilocarpine-induced status epilepticus in the rat, and that intra-hippocampal infusions of recombinant human VEGF significantly protected against the loss of hippocampal CA1 neurons in this model (Nicoletti JN, Shah SK, McCloskey DP, et al. Neuroscience 2008;151:232-41). We hypothesized that we would see a preservation of cognitive and emotional functioning with VEGF treatment accompanying the neuroprotection previously observed in this paradigm. Using the Morris water maze to evaluate learning and memory, and the light-dark task to assess anxiety, we found a selective profile of preservation. Specifically, VEGF completely preserved normal anxiety functioning and partially but significantly protected learning and memory after status epilepticus. To determine whether the ability of VEGF to attenuate behavioral deficits was accompanied by sustained preservation of hippocampal neurons, we stereologically estimated CA1 pyramidal neuron densities 4 weeks after status epilepticus. At this time point, we found no significant difference in neuronal densities between VEGF- and control-treated status epilepticus animals, suggesting that VEGF could have protected hippocampal functioning independent of its neuroprotective effect.

Serum neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in prognosticating immunotherapy efficacy.

Aim: To examine neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in prognosticating immunotherapy efficacy. Methods: A retrospective study of 156 patients with metastatic melanoma and non-small-cell lung cancer on PD-1 inhibitors. Results: Baseline NLR ≥5 was associated with worse progression-free survival (hazard ratio [HR]: 1.53; 95% CI: 1.01-2.31; p = 0.043) but nonsignificant worse overall survival trend (HR: 1.51; 95% CI: 0.98-2.34; p = 0.064). PLR ≥200 was associated with worse overall survival (HR: 1.94; 95% CI: 1.29-2.94; p = 0.002) and worse progression-free survival (HR: 1.894; 95% CI: 1.27-2.82; p = 0.002). NLR or PLR are prognosticating factors regardless of cancer types, with PLR having a stronger association with outcomes than NLR. Conclusion: High baseline NLR or PLR (alone and combined) were associated with worse immunotherapy efficacy regardless of cancer type, indicating their potential role as an agnostic marker for immunotherapy efficacy.

Nano-elastic liposomes as multidrug carrier of sodium stibogluconate and ketoconazole: A potential new approach for the topical treatment of cutaneous Leishmaniasis.

The present study evaluates the efficacy of sodium stibogluconate (SSG) co-loaded with ketoconazole (KTZ) in nano-elastic liposomes (NELs) for the topical treatment of cutaneous leishmaniasis (CL). SSG-KTZ co-loaded NELs were developed and assessed for various physicochemical properties and anti-leishmanial potential. The optimized nano-vesicles have an average size of 212.8 ± 3.1 nm and entrapment efficiency of 61.2 ± 2.9%. SSG-KTZ co-loaded NELs displayed 5.37-fold higher skin permeation of SSG as compared to drug solution. SSG and KTZ displayed a synergistic interaction and flow cytometry revealed enhanced killing of DsRed Leishmania mexicana in infected macrophages. In-vitro and in-vivo anti-leishmanial studies indicated a 10.67-fold lower IC50 value and a 35.33-fold reduced parasitic burden as compared with plain SSG solution, respectively. SSG-KTZ co-loaded NELs were found to be a promising approach for the topical treatment of CL.