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Objective: To explore the effect of geraniol on cyclophosphamide- induced cardiotoxicity. Methods: Mice were divided into five groups: the control group, the cyclophosphamide group (200 mg/kg cyclophosphamide, i.p. on day 7), the group treated with geraniol 100 and 200 mg/kg from day 1 to day 14, along with a single dose of cyclophosphamide on day 7, and the geraniol alone group (200 mg/kg geraniol from day 1 to day 14). At the end of the study, animals were sacrificed, and blood and heart were collected and analyzed for biochemical, histopathological, and immunohistochemical changes. Results: Treatment with 200 mg/kg geraniol significantly reduced the levels of cardiac injury markers, malondialdehyde, and inflammatory and apoptotic markers, while increasing antioxidant activities in mice with cyclophosphamide-induced cardiotoxicity. Moreover, it remarkably alleviated histopathological aberrations in cardiac tissue. Conclusions: Geraniol attenuates cyclophosphamide-induced cardiotoxicity via antioxidant, anti-inflammatory, and antiapoptotic effects.

Empagliflozin (EMP) is known for its poor safety and efficacy profile due to its fast body distribution and poor solubility. Accordingly, an oral long-acting and floating/raft-forming nano gel was optimized to release coated EMP nanoparticles, and the released EMP nanoparticles showed enhanced dissolution compared to raw EMP particles. To repurpose EMP for cancer treatment, EMP shows anti-cancer and anti-inflammatory effects against cancer cells. EMP nanoparticles were characterized using FT-IR, PXRD, SEM, EMP encapsulation assay, and release studies. The raft-forming gel encapsulating the EMP was optimized and characterized. The EMP co-polymeric nanoparticles were studied to investigate EMP anti-cancer and anti-inflammatory activities against stomach cancer cells. The solubility of EMP nanoparticles was enhanced in 0.1 N HCl and pH 6.8 by 5 and 12 folds, respectively, compared to raw EMP powder. The particle size and zeta-potential values of improved EMP nanoparticles were 135.40 ± 18.60 nm, and −19.30 ± 0.80 mV, respectively. FT-IR, PXRD, SEM and TEM characterizations revealed polymeric coating of EMP particles. The study suggested that this optimized controlled-release raft-forming gel is a promising local oral approach against stomach cancer. The repurposing of EMP co-polymeric nanoparticles for stomach cancer and associated gastritis treatment was justified.

Polymethyl methacrylate (PMMA) has garnered significant attention in the field of dentistry due to its wide applications. This paper proposes the incorporation of the nystatin coated copper oxide (CuO) particles having desirable conductivity and antifungal properties, as a filler in the PMMA denture to address their low thermal conductivity, low impact strength, low fatigue resistance, and microbial adhesion. The prepared nystatin coated CuO particles were characterized with several analytical techniques. The nystatin coated CuO particles were mixed in different ratios (0%, 1%, 2%, and 4%) in PMMA corresponding to groups C, E1, E2, and E3, respectively. The prepared samples of composite PMMA with nystatin coated CuO were evaluated to determine their transverse strength, impact strength, Vickers hardness (HV), and thermal conductivity. Furthermore, antifungal properties of CuO particles, nystatin coated CuO particles, and their acrylic composites were evaluated against Candida albicans. Scanning electron microscopy (SEM) analysis confirmed the particles’ spherical and irregular shapes. The particle sizes range from nano to micron level. Fourier-transform infrared spectroscopy (FTIR) and energy dispersive X-ray spectroscopy (EDX) analysis confirmed the coating of nystatin on CuO. X-ray diffraction (XRD) analysis showed the diffraction patterns and planes of CuO monoclinic shape structure. The composite prepared to have higher values of HV (19.53 ± 0.65, 20.16 ± 0.37, and 21.11 ± 0.75, respectively) as compared to the control. The impact strength values were measured high at 14.12 ± 5.55 kJ/m2 for 2% containing nystatin coated CuO acrylic resins compared to control and other groups. The conductivity increased linearly with the addition of CuO particles. The addition of CuO particles causes a reduction in flexural strength as compared to the control group. As the concentration of nystatin coated CuO (1%, 2%, and 4%) in acrylic samples increased, the antifungal properties were improved. Thus, the incorporation of optimized concentrations of nystatin coated CuO particles in acrylic resin resulted in the improved mechanical, thermal, and antifungal properties.

The current study was designed to develop a nanoconjugate of cordycepin-melittin (COR-MEL) and assess its healing property in wounded diabetic rats. The prepared nanoconjugate has a particle size of 253.5 ± 17.4 nm with a polydispersity index (PDI) of 0.35 ± 0.04 and zeta potential of 17.2 ± 0.3 mV. To establish the wound healing property of the COR-MEL nanoconjugate, animal studies were pursued, where the animals with diabetes were exposed to excision and treated with COR hydrogel, MEL hydrogel, or COR-MEL nanoconjugate topically. The study demonstrated an accelerated wound contraction in COR-MEL nanoconjugate -treated diabetic rats, which was further validated by histological analysis. The nanoconjugate further exhibited antioxidant activities by inhibiting the accumulation of malondialdehyde (MDA) and exhaustion of superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic activities. The nanoconjugate further demonstrated an enhanced anti-inflammatory activity by retarding the expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Additionally, the nanoconjugate exhibits a strong expression of transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF)-A, and platelet-derived growth factor (PDGFR)-β, indicating enrichment of proliferation. Likewise, nanoconjugate increased the concentration of hydroxyproline as well as the mRNA expression of collagen, type I, alpha 1 (Col 1A1). Thus, it is concluded that the nanoconjugate possesses a potent wound-healing activity in diabetic rats via antioxidant, anti-inflammatory, and pro-angiogenetic mechanisms.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of chemotherapies’ most often documented side effects. Patients with CIPN experience spontaneous burning, numbness, tingling, and neuropathic pain in their feet and hands. Currently, there is no effective pharmacological treatment to prevent or treat CIPN. Activating the cannabinoid receptor type 1 (CB1) by orthosteric agonists has shown promising results in alleviating the pain and neuroinflammation associated with CIPN. However, the use of CB1 orthosteric agonists is linked to undesirable side effects. Unlike the CB1 orthosteric agonists, CB1 positive allosteric modulators (PAMs) don’t produce any psychoactive effects, tolerance, or dependence. Previous studies have shown that CB1 PAMs exhibit antinociceptive effects in inflammatory and neuropathic rodent models. This study aimed to investigate the potential benefits of the newly synthesized GAT229, a pure CB1 PAM, in alleviating neuropathic pain and slowing the progression of CIPN. GAT229 was evaluated in a cisplatin-induced (CIS) mouse model of peripheral neuropathic pain (3 mg/kg/d, 28 d, i.p.). GAT229 attenuated and slowed the progression of thermal hyperalgesia and mechanical allodynia induced by CIS, as evaluated by the hotplate test and von Frey filament test. GAT229 reduced the expression of proinflammatory cytokines in the dorsal root ganglia (DRG) neurons. Furthermore, GAT229 attenuated nerve injuries by normalizing the brain-derived neurotrophic factor and the nerve growth factor mRNA expression levels in the DRG neurons. The CB1 receptor antagonist/inverse agonist AM251 blocked GAT229-mediated beneficial effects. According to our data, we suggest that CB1 PAMs might be beneficial in alleviating neuropathic pain and slowing the progression of CIPN.

Objectives: Adenosine receptor signaling and suppressing potential pathways such as the aryl hydrocarbon receptor (AHR) and takeda G-protein-coupled receptor-5(TGR5) have been identified as potential targets for enhancing metabolic health. Certain adenosine receptor (AR) ligands have been suggested to reduce inflammation and improve thermogenesis in adipose tissue. Methods: This study employed in-silico biomolecular fractions of adenosine receptors and other potential targets to understand the mechanism of action of Asperuloside. Additionally, the anti-obesity potential of Asperuloside, a dual-acting ligand with A2A adenosine receptor (A2AAR) agonist and A3 adenosine receptor (A3AR) agonist activities, were examined using computational analysis in the obesity model. The impact of Asperuloside on inflammation and thermogenesis was studied through diverse protein structures such as the A2AAR complex with agonist/A2AAR complex with antagonist, the rhodopsin mutant with bound galphact peptide (as A3 adenosine receptor), The Human TGR5 complex with synthetic agonist 23H, and AHR receptors antagonism. Results: The study found that Asperuloside has therapeutic affinity for the binding site of adenosine receptors and revealed a novel binding interaction that helps reduce inflammation and improve thermogenesis-mediated obesity. Conclusion: Asperuloside may have anti-obesity effects through its dual-acting ligand with A2AAR and A3AR agonist activities. This study provides a major step towards understanding the mechanism of action of Asperuloside and its potential use as an anti-obesity drug. In vivo tests will help ascertain its pharmacokinetic characteristics, metabolite production in animals, and the effects of chronic daily absorption.

This study aims to fabricate, characterize and evaluate Guided tissue regeneration (GTR) membrane containing eggshell (ES), chlorhexidine (CHX) and polymeric matrix for periodontal application. ES powder ground to size 74 µm was mixed in Polylactic Acid (PLA) and Polyethylene Glycol (70:30 ratios) mixture in 10% and 30% wt to fabricate the membrane and named groups C-10 and C-30. Along with this, 0.25% and 0.5% CHX powder were adsorbed on ES powder and incorporated in PLA and PEG mixture to fabricate drug containing groups C-10CHX and C-30CHX respectively. UTM was used to measure tensile strength, Young’s Modulus, and percent elongation of the prepared GTR membrane. Experimental groups containing 10% ES powder (C-10 and C-30) had adequate tensile properties. The percent mass change of the samples was calculated by the change in weight of the samples (Wd) from the weight of samples after immersion in phosphate-buffered saline PBS (Wt). Contact angle measurement showed that all membranes were found to be hydrophilic (contact angle70%).

Myocardial injury (MI) is an important pathological driver of mortality worldwide., and arises as a result of imbalances between myocardial oxygen demand and supply. In MI, oxidative stress often leads to inflammatory changes and apoptosis. Current therapies for MI are known to cause various adverse effects. Consequently, the development of new therapeutic agents with a reduced adverse event profile is necessary. In this regard, 2-methoxyestradiol (2ME), the metabolic end-product of oestradiol, possesses anti-inflammatory and antioxidant properties. The aim of this research is to assess the impact of 2ME on cardiac injury caused by isoproterenol (ISO) in rats. Animals were separated into six groups; controls, and those receiving 2ME (1 mg/kg), ISO (85 mg/kg), ISO + 2ME (0.25 mg/kg), ISO + 2ME (0.5 mg/kg), and ISO + 2ME (1 mg/kg). 2ME significantly attenuated ISO-induced changes in electrocardiographic changes and the cardiac histological pattern. This compound also decreased lactate dehydrogenase activity, creatine kinase myocardial band and troponin levels. The ability of 2ME to act as an antioxidant was shown by a decrease in malondialdehyde concentration, and the restoration of glutathione levels and superoxide dismutase activity. Additionally, 2ME antagonized inflammation and cardiac cell apoptosis, a process determined to be mediated, at least partially, by suppression of Gal-3/TLR4/MyD88/NF-κB signaling pathway. 2ME offers protection against acute ISO-induced MI in rats and offers a novel therapeutic management option.

Dry mouth is characterized by lower saliva production and changes in saliva composition. In patients with some salivary gland function remaining, pharmaceutical treatments are not recommended; therefore, new, more effective methods of promoting saliva production are needed. Hence, this study aimed to provide an overview of the histological changes in the salivary gland in the model of isoproterenol (ISO)-induced degenerative changes in male Wistar rats and to evaluate the protective effect of piceatannol. Thirty-two male Wistar rats were randomly divided into four groups: the control group, the ISO group, and the piceatannol (PIC)-1, and -2 groups. After the third day of the experiment, Iso (0.8 mg/100 g) was injected intraperitoneally (IP) twice daily into the animals. PIC was given IP in different daily doses (20 and 40 mg/kg) for three days before ISO and seven days with ISO injection. The salivary glands were rapidly dissected and processed for histological, histochemical, immunohistochemical (Ki-67), and morphometric analysis. Upon seven days of treatment with ISO, marked hypertrophy was observed, along with an increased number of positive Ki-67 cells. Proliferation was increased in some endothelial cells as well as in ducts themselves. Despite the significant decrease in proliferation activity, the control group did not return to the usual activity level after treatment with low-dose PIC. Treatment with a high dose of PIC reduced proliferative activity to the point where it was substantially identical to the results seen in the control group. An ISO-driven xerostomia model showed a novel protective effect of piceatannol. A new era of regenerative medicine is dawning around PIC’s promising role.

Background: Hepatic fibrosis is a major health problem all over the world, and there is no effective treatment to cure it. Hence, the current study sought to assess the anti-fibrotic efficacy of apigenin against CCl4-induced hepatic fibrosis in mice. Methods: Forty-eight mice were put into six groups. G1: Normal Control, G2: CCl4 Control, G3: Silymarin (100 mg/kg), G4 and G5: Apigenin (2 &20 mg/Kg), G6: Apigenin alone (20 mg/Kg). Groups 2, 3, 4, and 5 were given CCl4 (0.5 mL/kg. i.p.) twice/week for six weeks. The level of AST, ALT, TC, TG, and TB in serum and IL-1β, IL-6, and TNF-α in tissue homogenates were assessed. Histological studies by H&E staining and Immunostaining of liver tissues were also performed. Results: The CCl4-challenged group showed increased serum AST (4-fold), ALT (6-fold), and TB (5-fold). Both silymarin and apigenin treatments significantly improved these hepatic biomarkers. The CCl4-challenged group showed reduced levels of CAT (89%), GSH (53%), and increased MDA (3-fold). Both silymarin and apigenin treatments significantly altered these oxidative markers in tissue homogenates. The CCl4-treated group showed a two-fold increase in IL-1β, IL-6, and TNF-α levels. Silymarin and apigenin treatment considerably decreased the IL-1β, IL-6, and TNF-α levels. Apigenin treatment inhibited angiogenic activity, as evidenced by a decrease in VEGF (vascular endothelial growth factor) expression in liver tissues, and a decline in vascular endothelial cell antigen expression (CD34). Conclusions: Finally, these data collectively imply that apigenin may have antifibrotic properties, which may be explained by its anti-inflammatory, antioxidant, and antiangiogenic activities.

Nephrotoxicity is a serious complication that limits the clinical use of gentamicin (GEN). Parthenolide (PTL) is a sesquiterpene lactone derived from feverfew with various therapeutic benefits. However, PTL possesses low oral bioavailability. This study aimed to evaluate the therapeutic protective effects of PTL-phytosomes against GEN-induced nephrotoxicity in rats. The PTL was prepared as phytosomes to improve the pharmacological properties with a particle size of 407.4 nm, and surface morphology showed oval particles with multiple edges. Rats were divided into six groups: control, nano-formulation plain vehicle, PTL-phytosomes (10 mg/kg), GEN (100 mg/kg), GEN + PTL-phytosomes (5 mg/kg), and GEN + PTL-phytosomes (10 mg/kg). The administration of PTL-phytosomes alleviated GEN-induced impairment in kidney functions and histopathological damage, and decreased kidney injury molecule-1 (KIM-1). The anti-oxidative effect of PTL-phytosomes was demonstrated by the reduced malondialdehyde (MDA) concentration and increased superoxide dismutase (SOD) and catalase (CAT) activities. Furthermore, PTL-phytosomes treatment significantly enhanced sirtuin 1 (Sirt-1), nuclear factor erythroid-2-related factor-2 (Nrf2), NAD(P)H quinone dehydrogenase 1 (NQO1), and heme oxygenase-1 (HO-1). Additionally, PTL-phytosomes treatment exhibited anti-inflammatory and anti-apoptotic properties in the kidney tissue. These findings suggest that PTL-phytosomes attenuate renal dysfunction and structural damage by reducing oxidative stress, inflammation, and apoptosis in the kidney.

Innovative drug delivery systems based on iron oxide nanoparticles (INPs) has generated a lot of interest worldwide and have prime biomedical benefits in anticancer therapy. There are still issues reported regarding the stability, absorption, and toxicity of iron oxide nanoparticles (INPs) when administered due to its rapid surface oxidation and agglomeration with blood proteins. To solve this problem, we have synthesized trehalose-coated stabilized iron oxide nanoparticles (TINPs) by a co-precipitation technique. The surface coating of INPs with trehalose helps to improve the stability, prevents protein binding, and increase absorption uptake inside the body. Developed TINPs was then loaded with anticancer drug cytarabine by chemical crosslinking encapsulation method using suitable solvent. Engineered cytarabine-loaded trehalose-coated stabilized iron oxide nanoparticles (CY-TINPs) were optimized for particle size, zeta potential (−13.03 mV), and solid-state characterization such as differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and transmission electron microscope (TEM) studies. The particle size of 50 nm was achieved for developed CY-TINPs. The developed CY-TINPs was further evaluated for in vitro cell line investigations which confirmed potential cytotoxic activity. Developed CY-TINPs show remarkable enhancement in in vivo pharmacokinetic parameters Cmax as 425.26 ± 2.11 and AUC0–72 as 11,546.64 ± 139.82 as compared to pure drug. Compared to traditional drug delivery, the CY-TINPs formulation can effectively delay release, improve bioavailability, and boost cytotoxic activity against tumors.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. Oxidative stress plays an important role in the pathophysiology of DPN. Red Sea marine sponge Xestospongia testudinaria extract has a promising neuroprotective effect, presumably owing to its antioxidant and anti-inflammatory properties. Thus, this study aimed to investigate the neuroprotective effect of the sponge X. testudinaria extract on in vitro and in vivo models of DPN. Mice dorsal root ganglia (DRG) were cultured with high glucose (HG) media and used as an in vitro model of DPN. Some of the DRGs were pre-treated with 2 mg/mL of X. testudinaria. The X. testudinaria extract significantly improved the HG-induced decreased neuronal viability and the neurite length. It improved the oxidative stress biomarkers in DRG cultures. The DPN model was induced in vivo by an injection of streptozotocin at a dose of 150 mg/kg in mice. After 35 days, 0.75 mg/kg of the X. testudinaria extract improved the hot hyperalgesia and the DRG histology. Although the sponge extract did not reduce hyperglycemia, it ameliorated the oxidative stress markers and pro-inflammatory markers in the DRG. In conclusion, the current study demonstrates the neuroprotective effect of Red Sea sponge X. testudinaria extract against experimentally induced DPN through its antioxidant and anti-inflammatory mechanisms.

The present study aimed to optimize luliconazole nanoemulsion using Box–Behnken statistical design, which was further incorporated into the polymeric gel of Carbopol 934. The formulation was characterized for its size, entrapment efficiency, ex vivo permeation, and mechanism of release. The size of the dispersed globules of the optimized drug-loaded nanoemulsion was found to be 17 ± 3.67 nm with a polydispersity index (PDI) less than 0.5. Although the surface charge was recorded at –9.53 ± 0.251, the stability was maintained by the polymeric matrix that prevented aggregation and coalescence of the dispersed globules. The luliconazole-nanoemulgel (LUL-NEG) was characterized for drug content analysis, viscosity, pH, and refractive index, where the results were found to be 99.06 ± 0.59%, 9.26 ± 0.08 Pa.s, 5.65 ± 0.17, and 1.31 ± 0.08, respectively. The permeation across the rat skin was found to be significantly higher with LUL-NEG when compared with LUL gel. Furthermore, the skin irritation test performed in experimental animals revealed that the blank NEG, as well as the LUL-NEG, did not produce any signs of erythema following 48 h exposure. In addition, the histopathological findings of the experimental skins reported no abnormal signs at the formulation application site. Finally, the NEG formulation was found to create a statistically significant zone of inhibition (P

The aim of the study was to develop and evaluate the Ginkgo biloba nanocomplex gel (GKNG) as a long-acting formulation for the wound healing potential. Pharmaceutical analysis showed an average particle size of 450.14 ± 36.06 nm for GKNG, zeta potential +0.012 ± 0.003 mV, and encapsulation efficiency 91 ± 1.8%. The rheological analysis also showed the optimum diffusion rate and viscosity needed for topical drug delivery. Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometry (PXRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) analysis further confirmed the success of GKNG. The in vivo study showed increments in the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) and a lower level of lipid peroxidation (MDA) after GKNG treatment. The GKNG group showed upregulations in collagen type I, as alpha 1 collagen (COL1A1), and collagen type IV, as alpha 1 collagen (COL4A1). Furthermore, the in vivo study showed increments in hydroxyproline, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta 1 (TGF-β1) after the GKNG. Additionally, GKNG effectively increased the wound contraction compared to GK gel and sodium alginate (SA) gel. Based on the in vitro and in vivo evaluation, GKNG effectively accelerated wound healing by modulation of antioxidant enzymes, collagens, angiogenic factors, and TGF-β1.

One of the major aggressive factors that affect gastric injury is non-steroidal anti-inflammatory drugs (NSAIDs). Indomethacin (Indo) showed higher potentiality in gastric injury over conventional NSAIDs. Piceatannol (PIC) is a natural polyphenolic stilbene that possesses potent antioxidant and anti-inflammatory properties. The gastroprotective properties of PIC have been overlooked previously. Hence, we aim to study gastric injury induced by Indo and the protective action manifested by PIC, as well as to elucidate the likely underlying mechanisms of action in a rat model. The rats have been treated with vehicle, Indo alone, combined treatment with Indo, and PIC at (5 mg/kg or 10 mg/kg), respectively. The rats were also treated with Indo and omeprazole. In our study, we found that PIC at both 5 and 10 mg/kg doses was effective by averting the rise in ulcer and lesion indices, acid production, and histological variations persuaded by Indo. Mechanistically, PIC significantly reduced lipid peroxidation product (MDA), increased the GSH content, and enhanced SOD and CAT activity. In addition, PIC exhibits a distinct reduction in the levels of inflammatory parameters (Cox-2, IL-6, TNF-α, and NFκB). Contrastingly, PIC augmented both mucin and PGE2 content. Moreover, PIC fostered angiogenesis by increasing the expression of proangiogenic factors (VEGF, bFGF, and PDGF). Overall, the above results suggest PIC exhibits a potential protective effect against Indo-induced gastric ulcers by the antioxidant, anti-inflammatory, and angiogenic mechanisms.

This study aimed to develop and evaluate sustained-release (SR) long-acting oral nanocomposites in-situ gelling films of resveratrol (Rv) to treat colorectal cancer. In these formulations, Rv-Soy protein (Rv-Sp) wet granules were prepared by the kneading method and then encapsulated in the sodium alginate (NA) dry films. The prepared nanocomposite in-situ gels films were characterized using dynamic light scattering, Fourier-transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy. The optimized formulations were further evaluated based on drug encapsulation efficiency, pH-drug release profile, swelling study, and storage time effects. The optimized formulation was tested for its anticancer activity against colorectal cancer cells using the cytotoxicity assessment, apoptosis testing, cell cycle analysis, gene expression analysis, and protein estimation by the reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay methods, respectively. The optimum film showed encapsulation efficiency of 97.87% ± 0.51 and drug release of 14.45% ± 0.043 after 8 h. All physiochemical characterizations confirmed, reasoned, and supported the drug release experiment’s findings and the encapsulation assay. The Rv nanocomposite formulation showed concentration-dependent cytotoxicity enhanced apoptotic activity as compared to free Rv (p < 0.05). In addition, Rv nanocomposite formulation caused a significant increase in Bcl-2-associated protein X (Bax) and a decrease in expression of B-cell lymphoma 2, interleukin 1 beta, IL-6, and tumor necrosis factor-alpha (Bcl2, IL-1β, IL-6, and TNF-α respectively) compared to that of free Rv in HCT-116 cells. These results suggest that long-acting Rv nanocomposite gels could be a promising agent for colorectal cancer treatment.

Pain is a common distress in chronic inflammatory diseases, and etoricoxib (ETB) is frequently used in its management. It possesses fewer adverse effects when compared with other non-steroidal anti-inflammatory drugs (NSAIDs). In the present study, ETB-loaded nanoemulsion (ETB-NE) was formulated and optimized. Eucalyptus oil, Tween 20, and PEG 200 were chosen as the oil, surfactant, and co-surfactant, respectively. The formulation was optimized using the Box–Behnken design. The optimized ETB-NE contained oil, Smix, and water in concentrations of 11.5, 38, and 50% respectively. It had droplet size, polydispersity index, and zeta potential values of 179.6 ± 4.21 nm, 0.373 ± 0.02, and −10.9 ± 1.01 mV, respectively. The optimized ETB-NE sample passed the thermodynamic stability and dispersibility tests. Transmission electron microscopy confirmed the spherical morphology of the NE droplets. The ETB-NE showed a biphasic drug release pattern and released 85.3 ± 1.8% of ETB at 12 h. The ETB-NE was formulated into nanoemulsion gel (NEG) by using 1% carbopol 934. ETB-NEG was characterized for pH, viscosity, drug content, and percentage entrapment efficiency. During in vitro permeation studies, the apparent permeability coefficient value was 0.072 cm−2 h−1 for ETB-NEG, while it was only 0.047 cm−2 h−1 for the ETB gel. The skin histopathology study results confirmed that the ETB-NEG formulation was non-irritant and safe for topical use. The maximum possible analgesia observed for ETB-NEG was significantly high (p < 0.05) with a value of 47.09% after 60 min. Similarly, a formalin-induced acute inflammatory pain study in rats also demonstrated higher analgesia for the ETB-NEG, with % inhibition values of 37.37 ± 5.9 and 51.95 ± 4.4 in the acute and late phases, respectively. Further, ETB-NEG showed 78.4 ± 3.5% inhibition at 8 h in the in vivo anti-inflammatory testing by rat paw edema method. The ETB-NEG was found to enhance the in vivo analgesic and anti-inflammatory effects of ETB. The study results could stimulate further studies in this area for establishing a clinically successful NEG formulation of ETB.