Recent Developments in Nanotechnology-Based Biosensors for the Diagnosis of Coronavirus.

The major challenge in today's world is that medical research is facing the existence of a vast number of viruses and their mutations, which from time to time cause outbreaks. Also, the continuous and spontaneous mutations occurring in the viruses and the emergence of resistant virus strains have become serious medical hazards. So, in view of the growing number of diseases, like the recent COVID-19 pandemic that has caused the deaths of millions of people, there is a need to improve rapid and sensitive diagnostic strategies to initiate timely treatment for such conditions. In the cases like COVID-19, where a real cure due to erratic and ambiguous signs is not available, early intervention can be life-saving. In the biomedical and pharmaceutical industries, nanotechnology has evolved exponentially and can overcome multiple obstacles in the treatment and diagnosis of diseases. Nanotechnology has developed exponentially in the biomedical and pharmaceutical fields and can overcome numerous challenges in the treatment and diagnosis of diseases. At the nano stage, the molecular properties of materials such as gold, silver, carbon, silica, and polymers get altered and can be used for the creation of reliable and accurate diagnostic techniques. This review provides insight into numerous diagnostic approaches focused on nanoparticles that could have been established for quick and early detection of such diseases.

Correction to: a facile approach for fabricating CD44-targeted delivery of hyaluronic acid-functionalized PCL nanoparticles in urethane-induced lung cancer: Bcl-2, MMP-9, caspase-9, and BAX as potential markers.

In the original article the blots for BAX were inadvertently flipped in Fig. 11a. The inadvertent error in the case of BAX does not change any of the results.

Biotin anchored nanostructured lipid carriers for targeted delivery of doxorubicin in management of mammary gland carcinoma through regulation of apoptotic modulator.

Mammary gland tumour has the highest incidence rate and mortality in women, worldwide. The present study envisaged a molecularly targeted nanostructured lipid carrier (NLCs) for doxorubicin (Dox) delivery capable of inducing cellular apoptosis in mammary gland tumour. NLCs were prepared utilizing Perilla frutescens oil (54-69% ω3-fatty acid) as liquid lipid to enhance entrapment of Dox through molecular ion pairing. Biotin decorated NLCs (b-Dox-NLCs) were evaluated in vitro and in vivo. The b-Dox-NLCs showed particle size of 105.2 ± 3.5 nm, zeta potential -35 ± 2 mV, entrapment 99.15 ± 1.71%, drug content 19.67 ± 2.6 mg.g-1, biotin content 5.85 ± 0.64 µg.g-1 and drug release 98.67 ± 2.43% (facilitated by acidic microenvironment) respectively. MTT assay and Flow cytometric analysis revealed higher anti-proliferative capability of b-Dox-NLCs to force apoptosis in MCF-7 cell line vis-à-vis marketed Dox, evidenced by reactive oxygen species level and mitochondrial membrane potential mediated apoptosis. Enhanced antitumor targeting, therapeutic safety and efficacy was exhibited by b-Dox-NLCs, as investigated through tumour volume, animal survival, weight variation, cardiotoxicity and biodistribution studies in 7,12-Dimethylbenz[a]anthracene induced mammary gland tumour. Immunoblotting assay demonstrated b-Dox-NLCs downregulated anti-apoptotic proteins, i.e. bcl-2, MMP-9 while upregulated pro-apoptotic proteins, i.e. caspase-9, p16 and BAX. The experimental results suggest that biotinylated ω3-fatty acid augmented NLCs loaded with Dox are capable of inducing programmed cell death in mammary tumour and can be utilized as safe and effective delivery system with enhanced potential for mammary gland carcinoma therapy.

Optimization of Inositol Hexaphosphate Colon Targeted Formulation for Anticarcinogenic Marker Modulation.

Colorectal cancer has become the third most frequent reason of cancer death in men and women. Currently, natural compounds are being looked up to, for subversion and deterrence of cancers. Inositol hexaphosphate (IP6) is one such naturally occurring phosphorylated carbohydrate present in most legumes and cereals which acts as a potential antineoplastic agent and can be used effectively to prevent and treat colon carcinomas. Despite the immense potential, due to the prevalence of high charge and ability to form salts and chelates with various divalent metals, it gets excreted out quickly from the body. On reaching the colon in its original form, it can serve as an effective anticancer agent. Therefore, a suitable dosage form that can prevent the drugs from being absorbed from the upper gastrointestinal tract is required to be prepared, to target it to the colon. Thus, microspheres of IP6 using a biodegradable polymer that degrades in the colon were attempted using the solvent evaporation method. The formulation was investigated for percentage yield, encapsulation efficiency, particle size distribution modification, and release rate. Optimized formulation showed particle size of 92 ± 0.76 µm, entrapment efficiency of 67.26% ± 0.75, percent drug loading of 15.74%, and in vitro drug release 82.36 ± 0.51. The results of the in vivo study divulged that IP6 loaded pectin microspheres showed significant positive modulation of biomarker levels and restoration of colonic architecture to almost normal as observed through histopathology and scanning electron microscopy studies in DMH-induced colon tumors in Albino Wistar rats.

In vitro and in silico molecular interaction of multiphase nanoparticles containing inositol hexaphosphate and jacalin: Therapeutic potential against colon cancer cells (HCT-15).

Inositol hexaphosphate (IP6) is a natural constituent found in almost all cereals and legumes. It is known to cause numerous antiangiogenic manifestations. Notwithstanding its great potential, it is underutilized due to the chelation and rapid excretion from the body. Jacalin is another natural constituent obtained from seeds of jackfruit and can target disaccharides overexpressed in tumor cells. The current study was in-quested to develop and evaluate a surface-modified gold nanoparticulate system containing IP6 and jacalin which may maximize the apoptotic effect of IP6 against HCT-15 cell lines. IP6 loaded jacalin-pectin-gold nanoparticles (IJP-GNPs) were developed through reduction followed by incubation method. The developed formulation was tested for various in vitro and in silico studies to investigate its potential. HCT-15 cells when exposed to IJP-GNP resulted in significant apoptotic effects in dose as well as time-dependent manner, as measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, micronucleus, and reactive oxygen species assay. IJP-GNP displayed cell cycle arrest at the G0/G1 phase. To further explore the mechanism of chemoprevention, in silico studies were performed. The docking results revealed that the interactive behavior of IP6, P-GNP, and jacalin could target and inhibit the tumor formation activity, supported by in vitro studies. Taken together, all the findings suggested that IP6 loaded nanoparticles may increase the hope of future drug delivery strategy for targeting colon cancer.

A synergistic approach for management of lung carcinoma through folic acid functionalized co-therapy of capsaicin and gefitinib nanoparticles: Enhanced apoptosis and metalloproteinase-9 down-regulation.

BACKGROUND: Lung cancer is one of the most lethal cancers and lacks effective treatment strategy. Therapeutic efficacy can be improved through active targeting approach utilizing surface engineered nanoparticles (NPs) for cancer therapy. PURPOSE: The present study envisioned development of Folic acid (FA) functionalized NPs for co-administration of gefitinib (Gnb) and capsaicin (Cap) respectively to enhance the therapeutic outcome by disabling the barriers related to tumors extracellular matrix. RESEARCH METHODS AND PROCEDURE: The FA conjugated Gnb/Cap polymeric (PLGA-PEG) NPs were prepared using oil in water emulsion technique and methodically developed using Quality by Design (QbD) concept employing central composite design. The developed formulations were subjected to various in vitro (A549 cell lines) and in vivo evaluations in urethane-induced lung cancer. RESULTS: The modified NPs displayed particle sizes of 217.0 ±â€¯3.2 nm and 213.0 ±â€¯5.2 nm and drug release of 85.65 ±â€¯3.21% and 81.43 ±â€¯4.32% for Gnb and Cap respectively. Higher cellular uptake and lower cell viability in A549 cell line was displayed by functionalized NPs compared to free drug. Co administration of Gnb and Cap NPs displayed significant targeting potential, reduction in tumor volume while restoring the biochemical parameters viz., SOD, catalase, TBARS and protein carbonyl, towards normal levels when compared with toxic group. Significant down regulation was observed for anti-apoptotic proteins (MMP-9) and up regulation of pro-apoptotic proteins (caspase-3, caspase-9 and MMP-9) with co-therapy of Gnb and Cap NPs, when compared with individual therapy through Gnb/Cap. CONCLUSION: Potentiation of the action of Gnb when co administered with Cap NPs can be a promising breakthrough for developing safe, effective and targeted delivery for lung carcinoma therapy.

Pectin-encrusted gold nanocomposites containing phytic acid and jacalin: 1,2-dimethylhydrazine-induced colon carcinogenesis in Wistar rats, PI3K/Akt, COX-2, and serum metabolomics as potential targets.

Phytic acid (PA) has momentous chemotherapeutic potential. Due to the chelate formation and rapid elimination, it is not popular in cancer treatment. The present work was inquested to develop a surface-modified nanoformulation of PA which prevents its speedy elimination and maximizes chemotherapeutic action. Chloroauric acid was reduced with pectin to produce pectin-gold nanoparticles (PGNPs). PGNPs were incubated with PA and jacalin for drug loading and surface modifications, respectively, to form PA-loaded jacalin-pectin-gold nanoparticles (PA-J-PGNPs). Formulation(s) were assessed for various pharmaceutical/pharmacological parameters. To validate the efficacy against colon carcinogenesis, formulation(s) were assessed in 1,2-dimethylhydrazine (DMH)-treated Wistar rats. DMH treatment distorted colonic architecture, oxidative, and hemodynamic parameters, which were favorably restored by PA-J-PGNP administration. To further confirm our deliberations, formulation(s) were also examined against DMH-altered metabolic changes and expression of markers pertaining to cellular proliferation, which was reinstated by PA-J-PGNPs. Our findings establish PA formulation(s) as a promising approach for suppression of colon carcinogenesis.

A facile approach for fabricating CD44-targeted delivery of hyaluronic acid-functionalized PCL nanoparticles in urethane-induced lung cancer: Bcl-2, MMP-9, caspase-9, and BAX as potential markers.

Lung carcinoma ranks highest in cancer-related death (about 20% of total cancer deaths) due to poor prognosis and lack of efficient management therapy. Owing to the lack of effective therapeutic approaches, survival rate of less than 5 years persists over the years among non-small cell lung cancer (NSCLC) patients. Capsaicin (CAP) is well reported for its antiproliferative and antioxidant properties in various literature but lacks an appropriate delivery carrier. The present study was aimed to develop CAP-loaded hyaluronic acid (HA) nanoparticles (NPs) utilizing layer by layer technique to achieve enhanced and precise delivery as well as target specificity. The NPs were evaluated for in vitro release, particle size, zeta potential, and cytotoxicity on A549 cells. The optimized NPs exhibited a particle size of 194 ± 2.90 nm, - 27.87 ± 3.21 mV zeta potential, and 80.70 ± 4.29% release, respectively, over a period of 48 h. Flow cytometric analysis revealed superior performance of HA-PCL-CAP in terms of suppressed cell viability in A549 cell lines when compared with CAP and PCL-CAP. Further, HA-anchored NPs were evaluated in vivo for their therapeutic efficacy in urethane-induced lung carcinoma in rat model. The superlative therapeutic potential of HA-PCL-CAP was advocated from the results of reactive oxygen species and mitochondrial membrane-mediated apoptosis. HA-PCL-CAP-administered groups presented greater therapeutic efficacy as revealed through reduced tumor volume and improved animal survival rate. A greater drug accumulation in tumor tissue as revealed from biodistribution studies evidences targeting potential of HA-PCL-CAP in urethane-induced lung carcinoma. Graphical abstract ᅟ.

Biotinylated naringenin intensified anticancer effect of gefitinib in urethane-induced lung cancer in rats: favourable modulation of apoptotic regulators and serum metabolomics.

Co-therapy through biotin modified nanoparticles (NPs) of gefitinib (Gnb) and naringenin (Nar) was investigated for its therapeutic and synergistic potential against lung cancer. The biotin-conjugated polymeric NPs (bty-Nar/Gnb) were developed using oil in water emulsion technique and optimized using central composite design. The formulations were subjected to various in vitro (A549 cell lines) and in vivo evaluations in urethane-induced lung cancer. Co-administration of Gnb and Nar NPs displayed a significant reduction in tumour volume while restoring the biochemical parameters and serum metabolites to normal levels. Significant down-regulation of anti-apoptotic proteins (P-16, MMP-9 and Bcl-2) and up-regulation of pro-apoptotic proteins (caspase-9 and BAX) was displayed with co-therapy. This investigation demonstrated the superiority of co-therapy over individual therapy for improved therapeutic efficacy and is favourable for developing a safe, effective and targeted delivery for lung carcinoma therapy.

QbD-based development of α-linolenic acid potentiated nanoemulsion for targeted delivery of doxorubicin in DMBA-induced mammary gland carcinoma: in vitro and in vivo evaluation.

Breast cancer is the most common cancer of occurrence in women and has the highest mortality incidence rate therein. The present study envisaged to develop doxorubicin (Dox) loaded folate functionalized nanoemulsion (NE) for profound therapeutic activity against mammary gland cancer. NE was prepared using pseudo-ternary phase diagrams utilizing α-linolenic acid (ALA) as lipid phase, to further enhance the anticancer potential of Dox. Box-Behnken design was employed to systematically develop the NE. Optimized NE (f-Dox-NE) was evaluated for in vitro and in vivo performance. f-Dox-NE, with globule size 55.2 ± 3.3 nm, zeta potential - 31 ± 2 mV, entrapment 92.51 ± 3.62%, drug loading 0.42 ± 0.08% and percent drug release 94.86 ± 1.87% in 72 h, was capable of reducing cell viability in MCF-7 cell lines vis-à-vis pure and marketed drug. Further, mechanistic studies in MCF-7 cell lines demonstrated that f-Dox-NE induces cellular apoptosis by reactive oxygen species generated and mitochondrial membrane mediated apoptosis. The antitumor effect was evaluated in 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary gland tumor in female Albino Wistar rats. f-Dox-NE exhibited enhanced antitumor targeting potential, therapeutic safety and efficacy vis-à-vis pure and marketed drug, as revealed by tumor volume, animal survival, weight variation, cardiotoxicity and biodistribution studies. f-Dox-NE restored the biochemical parameters viz., SOD, catalase, TBARS and protein carbonyl, towards normal levels in comparison to DMBA induced animal group. f-Dox-NE displayed downregulation of anti-apoptotic (Bcl-2 and MMP-9) proteins and upregulation of pro-apoptotic proteins (caspase-9 and BAX). The experimental results suggest that ALA augmented folate functionalized NE are able to overcome the challenges of developing safe and effective delivery system with enhanced potential for mammary gland carcinoma therapy.

Assessment of improved buccal permeation and bioavailability of felodipine microemulsion-based cross-linked polycarbophil gel.

The oral bioavailability of felodipine (FEL) is very low, i.e., about 15%. This could be due to low water solubility and hepatic first-pass effect. The objective of the present study was to develop FEL microemulsion-based gel, to bypass the first pass effect, for buccal delivery. The optimized FEL microemulsion (OPT-MEF) was used to prepare buccoadhesive gels, with varying concentrations of hydroxypropyl methylcellulose (HPMC) E4M and polycarbophil (PCP), and evaluated. The cross-linking of the PCP gelling agent was done by adjusting the pH with a neutralizing agent, triethanolamine (TEA). The formulations, namely drug suspension, OPT-MEF, microemulsion-based buccal gel containing 1% w/v (MEF-E4M1), 2% w/v (MEF-E4M2), and 3% w/v (MEF-E4M3) of HPMC K4M and 1% w/v (MEF-PCP1), 2% w/v (MEF-PCP2), and 3% w/v (MEF-PCP3) of PCP were prepared and optimized on the basis of ex vivo permeation study, mucoadhesion force, and viscosity. The optimized buccal gel (MEF-PCP1) showed significantly higher (p < 0.01) permeation flux (J = 0.44 ± 0.16 mg/cm2/h), when compared with the drug suspension (J = 0.17 ± 0.14 mg/cm2/h). The permeation enhancement ratio of MEF-PCP1 was found to be 2.59 times higher than that of the aqueous suspension of the drug. The texture profile analysis of MEF-PCP1 was performed which showed spreadability (3.2 mJ), extrudability (151.8 mJ), hardness (13.8 g), and adhesiveness (41.0 g), and results indicated good spreadability and adhesiveness. The rheological study revealed the pseudoplastic flow behavior of MEF-PCP1 buccal gel. The Cmax value 9.21 ± 2.88 µg/ml of MEF-PCP1 gel was found to be significantly higher (P < 0.01) compared to the same dose administered by oral route (Cmax value 3.51 ± 1.74 µg/ml). The relative bioavailability (Fr) of the optimized MEF-PCP1 buccal gel was about 397.39% higher than that of oral route. In conclusion, consistent and effective buccal gel containing optimized FEL-loaded microemulsion, with improved buccal permeation and pharmacokinetic parameters was developed successfully to improve the bioavailability of FEL.

ω-3 Fatty Acid Synergized Novel Nanoemulsifying System for Rosuvastatin Delivery: In Vitro and In Vivo Evaluation.

The present study was undertaken to improve rosuvastatin (RSV) bioavailability and pharmacological response through formation of SNES using Perilla frutescens oil as lipid carrier. The composition of oil was estimated by fatty acid methyl ester (FAME) analysis using gas chromatography. Solubility of RSV in Perilla frutescens oil and Cremophor EL was 25.0 ± 3.0 and 60.0 ± 5.0 mg/mL, respectively. Later, nanophasic maps and a central composite design were employed to determine the maximum nanoemulsion region and further optimize SNES in this study. Finally, the optimized formulation was evaluated in vitro and in vivo. FAME analysis revealed that PUFA content was 70.3% of total fatty acid. Optimized SNES formulation demonstrated particle size of 17.90 nm, dissolution 98.80%, cloud point 45°C, emulsification time 2 min, and viscosity 241.41 ± 5.52 cP. The hypolipidemic property of SNES was further explored using Triton X-100-induced hyperlipidemic rat model, and there were reductions of serum cholesterol, triglyceride, and LDL and VLDL levels in the SNES-treated group as compared to the toxic control. Pharmacokinetic study of SNES revealed significantly higher C max (60.13 ± 25.43 ng/mL) and AUC0-∞ (6195 ± 42.38 ng h/mL) vis-à-vis marketed tablet (284.80 ± 13.44 ng/mL, 3131.72 ± 51.93 ng h/mL, respectively). RSV was successfully incorporated into ω-3 fatty acid-based SNES with improved pharmacokinetic parameters (~ 2-fold improved bioavailability) and better hypolipidemic properties, owing to the synergistic effects of hepatic lipid regulation itself. The results clearly explicated that ω-3 fatty acid-based SNES effectively enhanced bioavailability and pharmacological responses of RSV, suggesting that these formulations may be useful as alternative for hyperlipidemia treatment in future drug design perspective.

Augmented bioavailability of felodipine through an α-linolenic acid-based microemulsion.

The oral bioavailability of felodipine, a dihydropyridine calcium channel antagonist, is about 15%. This may be due to poor water solubility, and a lower intestinal permeability than a BCS class I drug, and hepatic first-pass metabolism of the drug. Many drugs are unpopular due to solubility issues. The goal of this study was to develop and optimize a felodipine-containing microemulsion to improve the intestinal permeability and bioavailability of the drug. The felodipine microemulsions were developed with the selected components, i.e., α-linolenic acid as the oil phase, Tween 80 as a surfactant, and isopropyl alcohol as co-surfactant using Box-Behnken design and characterized for in vitro release and particle size. The optimized felodipine-loaded microemulsion was investigated for physicochemical interaction, surface morphology, intestinal permeability, rheology, cytotoxicity, cellular uptake, pharmacodynamic (electrocardiogram and heart rate variability), and pharmacokinetic studies to explore its suitability as a promising oral drug delivery system for the treatment of hypertension. The optimized felodipine-loaded microemulsion showed significantly higher (P < 0.05) apparent permeability coefficients (Papp) at 7.918 × 10-5 cm/s after 1 h, when compared with conventional formulations that are marketed tablet, drug oily solution, and drug emulsion, which showed a maximum Papp of 3.013, 4.428, and 5.335 × 10-5 cm/s, respectively. The optimized felodipine-loaded microemulsion showed biocompatibility and no cytotoxicity. Cellular uptake studies confirmed payload delivery to a cellular site on the J774.A1 cell line. The rheology study of the optimized felodipine-loaded microemulsion revealed Newtonian-type flow behavior and discontinuous microemulsion formation. In pharmacodynamic studies, significant differences in parameters were observed between the optimized felodipine-loaded microemulsion and marketed formulation. The optimized felodipine-loaded microemulsion showed significantly higher (p < 0.01) C max (7.12 ± 1.04 µg/ml) than marketed tablets (2.44 ± 1.03 µg/ml). It was found that AUClast obtained from the optimized felodipine-loaded microemulsion (84.53 ± 10.73 µg h/ml) was significantly higher (p < 0.01) than the marketed tablet (27.41 ± 5.54 µg h/ml). The relative bioavailability (Fr) of the optimized felodipine-loaded microemulsion was about 308.3% higher than that of the marketed formulation. The results demonstrate that the prepared microemulsion is an advanced and efficient oral delivery system of felodipine for the management of hypertension.

Colloidal Vesicular System of Inositol Hexaphosphate to Counteract DMBA Induced Dysregulation of Markers Pertaining to Cellular Proliferation/Differentiation and Inflammation of Epidermal Layer in Mouse Model.

Cancer is a global health problem and chemoprevention is a promising approach for reducing cancer burden. Inositol hexaphosphate (IP6), a natural bioactive constituent of cereals, legumes, etc., has momentous potential as an antiangiogenic agent, that specifically affects malignant cells. The shortcoming is its quick absorption on oral/topical administration. Niosomes are flexible carriers for topical drug delivery. The central venture of current research was to optimize and characterize niosomal delivery system of IP6 for treatment of skin cancer. Thin film hydration method was utilized to prepare IP6 niosomes, and these were dispersed as a suspension in a suitable base. Developed formulations were analyzed for various physicochemical and pharmacological parameters such as particle size, encapsulation efficiency, morphology, drug release, texture analysis, irritability, cell line studies, Western blotting, RT-PCR, and histopathology. IP6 niosomal suspension and IP6 in acetone displayed IC50 value at the concentration of 0.96 mM (0.63 mg/mL) and 1.39 mM (0.92 mg/mL), respectively. IP6 niosomal suspension showed significantly higher (p < 0.05) activity and showed cytotoxic effect in SK-MEL-2 cancer cell line. Crucial events of cellular proliferation and differentiation, like expression of ornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA), cycloxygenase-2 (COX-2) and Cyclin D1 were initiated from the fourth hour through application of 7,12-dimethylbenzanthracene (DMBA) on albino mice. The DMBA altered expression of aforesaid enzymes was significantly (P < 0.001) prevented by concomitant application of niosomal formulations. Results of cell line study, Western blotting, RT-PCR, and histopathology suggested that IP6 niosomal suspension could constitute a promising approach for prevention of cellular proliferation as well as DMBA induced dysregulation of cellular proliferation/differentiation and inflammation.

Process optimization and photostability of silymarin nanostructured lipid carriers: effect on UV-irradiated rat skin and SK-MEL 2 cell line.

The objective of the present work was to formulate a novel stable delivery system which would not only overcome the solubility issue of silymarin, but also help to increase the therapeutic value by better permeation, anticancer action and reduced toxicity. This was envisaged through the recent developments in nanotechnology, combined with the activity of the phytoconstituent silymarin. A 2(3) full factorial design based on three independent variables was used for process optimization of nanostructured lipid carriers (NLC). Developed formulations were evaluated on the basis of particle size, morphology, in vitro drug release, photostability and cell line studies. Optimized silymarin-NLC was incorporated into carbopol gel and further assessed for rheological parameters. Stable behaviour in presence of light was proven by photostability testing of formulation. Permeability parameters were significantly higher in NLC as compared to marketed phytosome formulation. The NLC based gel described in this study showed faster onset, and prolonged activity up to 24 h and better action against edema as compared to marketed formulation. In case of anticancer activity of silymarin-NLC against SK-MEL 2 cell lines, silymarin-NLC proved to possess anticancer activity in a dose-dependent manner (10-80 µM) and induced apoptosis at 80 µM in SK-MEL 2 cancer cells. This work documents for the first time that silymarin can be formulated into nanostructured lipoidal carrier system for enhanced permeation, greater stability as well as anticancer activity for skin.

Development and evaluation of ultra-small nanostructured lipid carriers: novel topical delivery system for athlete's foot.

Athlete's foot is a fungal infection of the foot which causes dry, itchy, flaky condition of the skin caused by Trichophyton species. In this study, the potential of ultra-small nanostructured lipid carrier (usNLC)-based topical gel of miconazole nitrate for the treatment of athlete's foot was evaluated. Nanostructure lipid carriers (NLCs) prepared by melt emulsification and sonication technique were characterized for particle size, drug entrapment, zeta potential and drug release. The optimized usNLC revealed particle size 53.79 nm, entrapment efficiency 86.77%, zeta potential -12.9 mV and polydispersity index (PDI) of 0.27. The drug release studies of usNLC showed initial fast release followed by sustained release with 91.99% drug released in 24 h. Optimized usNLCs were incorporated into carbopol-934 gel and evaluated for pH (6.8), viscosity (36,400 mPa s) and texture analysis. Antifungal activity against Trichophyton mentagrophytes exhibited wider zone of inhibition, 6.6 ± 1.5 mm for optimized usNLC3 gel viz-à-viz marketed gel formulation (3.7 ± 1.2 mm). Hen's egg test-chorioallantoic membrane (HET-CAM) irritation test confirmed optimized usNLC gel to be non-irritant to chorioallantoic membrane. Improved dermal delivery of miconazole by usNLC gel could be achieved for treatment of athlete's foot.