Clinical Value of Timely Targeted Therapy for Patients With Advanced Non-Small Cell Lung Cancer With Actionable Driver Oncogenes.

BACKGROUND: A recent real-world study observed that 24% of patients with advanced non-small cell lung cancer (aNSCLC) with actionable driver oncogenes (ADOs) initiated nontargeted therapies before biomarker test results became available. This study assessed the clinical impact of the timing of first-line (1L) targeted therapies (TTs) in aNSCLC. MATERIALS AND METHODS: This retrospective analysis of a nationwide electronic health record-derived deidentified database included patients aged ≥18 years diagnosed with aNSCLC with ADOs (ALK, BRAF, EGFR, RET, MET, ROS-1, and NTRK) from January 1, 2015, to October 18, 2022, by biomarker testing within 90 days after advanced diagnosis and received 1L treatment. Cohorts were defined by treatment patterns ≤42 days after test results: "Upfront TT" received 1L TT ≤42 days; "Switchers" initiated 1L non-TT before or after testing but switched to TT ≤42 days; and "Non-switchers" initiated non-TT before or after testing and did not switch at any time. Adjusted multivariate Cox regression evaluated real-world progression-free survival, real-world time to next treatment or death, and real-world overall survival. RESULTS: A total of 3540 patients met the study criteria; 78% were treated in a community setting, and 50% underwent next-generation sequencing (NGS). There was no significant difference in outcomes between Switchers and Upfront TT; inferior outcomes were observed in Non-switchers versus Upfront TT. CONCLUSION: Our findings demonstrated improved outcomes with upfront 1L TT versus non-TT in patients with aNSCLC with ADOs and observed timely switching to TT after biomarker test result had similar outcomes to Upfront TT. Opportunities remain to improve the use of NGS for early ADO identification and determination of 1L TT.

Assembly of ordered DNA-curli fibril complexes during Salmonella biofilm formation correlates with strengths of the type I interferon and autoimmune responses.

Deposition of human amyloids is associated with complex human diseases such as Alzheimer's and Parkinson's. Amyloid proteins are also produced by bacteria. The bacterial amyloid curli, found in the extracellular matrix of both commensal and pathogenic enteric bacterial biofilms, forms complexes with extracellular DNA, and recognition of these complexes by the host immune system may initiate an autoimmune response. Here, we isolated early intermediate, intermediate, and mature curli fibrils that form throughout the biofilm development and investigated the structural and pathogenic properties of each. Early intermediate aggregates were smaller than intermediate and mature curli fibrils, and circular dichroism, tryptophan, and thioflavin T analyses confirmed the establishment of a beta-sheet secondary structure as the curli conformations matured. Intermediate and mature curli fibrils were more immune stimulatory than early intermediate fibrils in vitro. The intermediate curli was cytotoxic to macrophages independent of Toll-like receptor 2. Mature curli fibrils had the highest DNA content and induced the highest levels of Isg15 expression and TNFα production in macrophages. In mice, mature curli fibrils induced the highest levels of anti-double-stranded DNA autoantibodies. The levels of autoantibodies were higher in autoimmune-prone NZBWxF/1 mice than wild-type C57BL/6 mice. Chronic exposure to all curli forms led to significant histopathological changes and synovial proliferation in the joints of autoimmune-prone mice; mature curli was the most detrimental. In conclusion, curli fibrils, generated during biofilm formation, cause pathogenic autoimmune responses that are stronger when curli complexes contain higher levels of DNA and in mice predisposed to autoimmunity.

Antifungal activity of synthetic xanthenone against fluconazole-resistant Candida auris and its mechanism of action.

Candida auris, an emerging multidrug-resistant fungal pathogen discovered in Japan in 2009, poses a significant global health threat, with infections reported in about 25 countries. The escalation of drug-resistant strains underscores the urgent need for new treatment options. This study aimed to investigate the antifungal potential of 2,3,4,4a-tetrahydro-1H-xanthen-1-one (XA1) against C. auris, as well as its mechanism of action and toxic profile. The antifungal activity of XA1 was first evaluated by determining the minimum inhibitory concentration (MIC), time-kill kinetics and biofilm inhibition. In addition, structural changes, membrane permeability, reactive oxygen species (ROS) production, and in vitro and in vivo toxicity of C. auris after exposure to XA1 were investigated. The results indicated that XA1 exhibited an MIC of 50 µg/mL against C. auris, with time-kill kinetics highlighting its efficacy. Field emission scanning electron microscopy (FE-SEM) showed structural damage in XA1-treated cells, supported by increased membrane permeability leading to cell death. Furthermore, XA1 induced ROS production and significantly inhibited biofilm formation. Importantly, XA1 exhibited low cytotoxicity in human epidermal keratinocytes (HaCaT), with a cell viability of over 90% at 6.25 µg/mL. In addition, an LD50 of 17.68 µg/mL was determined in zebrafish embryos 24 hours post fertilization (hpf), with developmental delay observed at prolonged exposure at 6.25 µg/mL (48-96 hpf). These findings position XA1 as a promising candidate for further research and development of an effective antifungal agent.

Lyso-H2S: A Mycophenolic Acid-Derived Probe for Ultra-Low Toxicity, Intracellular H2S Detection, and Zebrafish Model Validation.

In several biological processes, H2S is known to function as an endogenous gaseous agent. It is very necessary to monitor H2S and relevant physiological processes in vivo. Herein, a new type of fluorophore with a reliable leaving group allows for excited-state intramolecular transfer characteristics (ESIPT), inspired by mycophenolic acid. A morpholine ring was connected at the maleimide position to target the lysosome. Subsequently, the dinitrophenyl group known for a photoinduced electron transfer (PET) effect, was connected to allow for an effective "turn-on" probe Lyso-H2S. Lyso-H2S demonstrated strong selectivity towards H2S, large Stokes shift (111 nm), and an incredibly low detection limit (41.8 nM). The imaging of endogenous and exogenous H2S in living cells (A549 cell line) was successfully achieved because of the specificity and ultra-low toxicity (100 % cell viability at 50 µM concentration of Lyso-H2S.) Additionally, Lyso-H2S was also employed to visualize the activity of H2S in the gallbladder and intestine in a living zebrafish model. This is the first report of a fluorescent probe to track H2S sensing in specific organ systems to our knowledge.

Clinical spectrum, phenotypic and molecular characterization, and antifungal susceptibility of an emerging human pathogen, Acrophialophora, from India.

Acrophialophora is implicated in superficial and invasive infections, especially in immunosuppressed individuals. The present study was undertaken to provide clinical, microbiological, phylogenetic, and antifungal susceptibility testing (AFST) profile of Acrophialophora isolated from India. All the isolates identified as Acrophialophora species at the National Culture Collection for Pathogenic Fungi, Chandigarh, India were revived. Phenotypic and molecular characterization was performed, followed by temperature studies, scanning electron microscopy (SEM), and AFST. We also performed systematic review of all the cases of Acrophialophora species reported till date. A total of nine isolates identified as Acrophialophora species were identified by molecular method as A. fusispora (n = 8) and A. levis (n = 1), from brain abscess (n = 4), respiratory tract (n = 3), and corneal scraping (n = 2). All patients but two had predisposing factors/co-morbidities. Acrophialophora was identified as mere colonizer in one. Temperature studies and SEM divulged variation between both species. Sequencing of the internal transcribed spacer ribosomal DNA and beta-tubulin loci could distinguish species, while the LSU ribosomal DNA locus could not. AFST showed the lowest minimum inhibitory concentrations (MICs) for triazoles and the highest for echinocandins. Systematic literature review revealed 16 cases (11 studies), with ocular infections, pulmonary and central nervous system infections, and A. fusispora was common species. All the patients except three responded well. High MICs were noted for fluconazole, micafungin, and caspofungin. This is the first study delineating clinical, phenotypic, and genotypic characteristics of Acrophialophora species from India. The study highlights microscopic differences between both species and emphasizes the role of molecular methods in precise identification. Triazoles appear to be the most effective antifungals for managing patients.

We describe clinical, phenotypic, and genotypic characteristics of Acrophialophora species. This species causes mild infection to fatal infection in immunosuppressed individuals. Triazoles are effective in treating such infections.

Invasive fungal disease in children with solid tumors: An Australian multicenter 10-year review.

Invasive fungal disease (IFD) occurs less frequently during treatment for solid compared to hematological malignancies in children, and risk groups are poorly defined. Retrospective national multicenter cohort data (2004-2013) were analyzed to document prevalence, clinical characteristics, and microbiology of IFD. Amongst 2067 children treated for solid malignancy, IFD prevalence was 1.9% overall and 1.4% for proven/probable IFD. Of all IFD episodes, 42.5% occurred in patients with neuroblastoma (prevalence 7.0%). Candida species comprised 54.8% of implicated pathogens in proven/probable IFD. In children with solid tumors, IFD is rare, and predominantly caused by yeasts.Routine prophylaxis may not be warranted.

Predictors of functional impairment and mortality in patients on maintenance hemodialysis.

INTRODUCTION: Numerous factors impact the mortality and functional abilities of patients with end-stage renal disease (ESRD) receiving maintenance hemodialysis (MHD). We aimed to determine the mortality rate at 1 year of MHD, identify predictors of mortality, and assess functional impairments concerning activities of daily living (ADLs) and instrumental ADL (IADL). METHODS: Our study was prospective, observational cohort study that enrolled patients receiving MHD. We collected demographic, clinical, and laboratory data. We also assessed ADLs and IADLs for daily performance. RESULTS: Our study included 167 patients with a mean age of 51.6 ± 13.1 years, and 56.9% were male. Of these, 80 (47.9%) were diabetic, and 145 (86.8%) were hypertensive. The mortality rate after 1 year of MHD was 10.8%, and cardiovascular causes accounted for over 70% of total deaths. Sudden cardiac death was the most frequent cause (38.9%), followed by cardiogenic shock (22.2%). Older age and low parathormone levels (<300 pg/mL) were significantly associated with higher mortality rates. Mean ADL and IADL scores were 4.5 ± 1.3 and 6.3 ± 2.7, respectively. Eighteen (10.8%) and 56 (33.5%) patients had low ADL and IADL scores, respectively. Although statistically insignificant, a higher proportion of non-survivors exhibited low IADL and ADL scores. Older age, longer diabetes duration, and higher BMI levels were significantly associated with lower IADL scores. CONCLUSIONS: Older age and suppressed PTH levels are predictors of mortality in ESRD patients receiving MHD. These patients require regular follow-ups to rule out cardiovascular morbidity. Functional impairment is prevalent but remains underdiagnosed in MHD patients. It should be monitored regularly to improve quality of life in ESRD.

Emulgels: a promising topical drug delivery system for arthritis management and care.

BACKGROUND: Emulgels, hybrid formulations of emulsions and gels, offer distinct benefits viz. extended release, enhanced bioavailability, and targeted drug delivery to inflamed joints, thereby minimizing systemic side effects, and maximizing therapeutic efficacy in targeting the diseases. Oral medications and topical creams have limitations viz. limited permeation, efficacy, and side effects. Arthritis is a prevalent chronic inflammatory disorder affecting a substantial global population of about 350 million necessitating the exploration of innovative and effective treatment approaches. Inflammation of one or more joints in the body is referred to generally as arthritis, associated with joint discomfort, edema, stiffness, and decreased motion in the joints. MAIN PART: Emulgels further improve drug solubility and penetration into the affected tissues, augmenting the potential for disease-modifying effects. This review article comprehensively examines recent research for the potential of emulgels (micro- and nanoemulgels) as a potential therapeutic approach for arthritis management, thus showcasing their promising potential in precise treatment regimens. Despite the considerable progress in emulgel-based arthritis therapies, the review emphasizes the need for additional research and translation to clinical trials, thus ascertaining their long-term safety, efficacy, and cost-effectiveness compared to conventional treatments. CONCLUSION: With ongoing advancements in drug delivery, emulgels present an exciting frontier in arthritis-associated conditions, with the potential to revolutionize arthritis treatment and significantly enhance patient life's quality.

In-depth Mechanism, Challenges, and Opportunities of Delivering Therapeutics in Brain Using Intranasal Route.

Central nervous system-related disorders have become a continuing threat to human life and the current statistic indicates an increasing trend of such disorders worldwide. The primary therapeutic challenge, despite the availability of therapies for these disorders, is to sustain the drug's effective concentration in the brain while limiting its accumulation in non-targeted areas. This is attributed to the presence of the blood-brain barrier and first-pass metabolism which limits the transportation of drugs to the brain irrespective of popular and conventional routes of drug administration. Therefore, there is a demand to practice alternative routes for predictable drug delivery using advanced drug delivery carriers to overcome the said obstacles. Recent research attracted attention to intranasal-to-brain drug delivery for promising targeting therapeutics in the brain. This review emphasizes the mechanisms to deliver therapeutics via different pathways for nose-to-brain drug delivery with recent advancements in delivery and formulation aspects. Concurrently, for the benefit of future studies, the difficulties in administering medications by intranasal pathway have also been highlighted.

Lineage-Independent Tumors in Bilateral Neuroblastoma.

Childhood tumors that occur synchronously in different anatomical sites usually represent metastatic disease. However, such tumors can be independent neoplasms. We investigated whether cases of bilateral neuroblastoma represented independent tumors in two children with pathogenic germline mutations by genotyping somatic mutations shared between tumors and blood. Our results suggested that in both children, the lineages that had given rise to the tumors had segregated within the first cell divisions of the zygote, without being preceded by a common premalignant clone. In one patient, the tumors had parallel evolution, including distinct second hits in SMARCA4, a putative predisposition gene for neuroblastoma. These findings portray cases of bilateral neuroblastoma as having independent lesions mediated by a germline predisposition. (Funded by Children with Cancer UK and Wellcome.).

Role of Albumin as a Targeted Drug Carrier in the Management of Rheumatoid Arthritis: A Comprehensive Review.

An endogenous transporter protein called albumin interacts with the Fc receptor to provide it with multiple substrate-binding domains, cell membrane receptor activation, and an extended circulating half-life. Albumin has the remarkable ability to bind with receptors viz. secreted protein acidic and rich in cysteine (SPARC) and scavenger protein-A (SR-A) that are overexpressed during rheumatoid arthritis (RA), enabling active targeting of the disease site instead of requiring specialized substrates to be added to the nanocarrier. RA, a chronic autoimmune illness, is characterized by the presence of a severe inflammatory response. RA patients have low serum albumin concentration, which signifies the high uptake of albumin at the inflammatory sites, giving a rationale to use albumin as a drug carrier for RA therapy. Albumin has the capacity for both passive and active targeting. It is an abundantly available protein in the bloodstream showing excellent cellular compatibility, degradability in biological tissues, nonantigenicity, and safety. There are three strategies of albumin mediated drug delivery as encapsulating therapeutics in albumin nanoparticles, chemically conjugating drugs with functional proteins, and albumin itself which is used as a targeting ligand to deliver drugs specifically to cells or tissues that express albumin-binding receptors. In the current review, an attempt has been made to highlight the significant evidence of albumin as a drug delivery carrier for the safe and effective management of RA. Evidence has been provided in the form of recent research advances, clinical trials, and patents. Additionally, this review will outline the prospective for the potential utilization of albumin as a drug vehicle for RA and suggest possible future avenues to provide the perspective for subsequent studies.

A Label-Free and Ultrasensitive Prussian Blue-Based Dipstick Sensor for Bacterial and Biofilm Detection.

Water and food contamination has become the major contributor to infections and deaths. However, rapid and sensitive bacterial detection still remains an unmet demand that has attracted widespread attention. Often water and food samples are sent out for laboratory testing to detect the presence of contamination, which is time-consuming and laborious. Herein, we have developed a highly sensitive, tenable, affordable, and robust (STAR) paper-based colorimetric dipstick sensor based on the principle of Prussian blue (PB) synthesis as an indicator of bacterial contamination. In the presence of bacteria, it leads to the formation of PB, a dye that acts as a colorimetric indicator. The intensity of the PB is the direct measure of the degree of contamination. The fabrication of the STAR dipstick sensor involves a simple and cost-effective process. The STAR dipstick sensor is ultrasensitive and can detect up to 101 CFU/mL of bacteria within minutes of contact with the test sample. The STAR dipstick sensor is fabricated using biodegradable components, which is speculated to facilitate quick and environmentally friendly degradation after each use. The sensor has been validated for its properties and capabilities at different pH to detect both Gram-positive and Gram-negative bacterial strains in real-time samples. The stability and degradation were also monitored. Comprehensively, the proposed STAR dipstick sensor can serve as a point-of-care device to detect bacterial contamination in a swift and sensitive manner.

"Lighting up" fluoride: cellular imaging and zebrafish model interrogations using a simple ESIPT-based mycophenolic acid precursor-based probe.

The discovery and implementation of media that derive from bioinspired designs and bear optical readouts featuring large Stokes shifts are of continued interest to a wide variety of researchers and clinicians. Myco-F, a novel mycophenolic acid precursor-based probe features a cleavable tert-butyldimethylsiloxy group to allow for fluoride detection. Myco-F exhibits high selectivity and specificity towards F- (Stokes shift = 120 nm). All measurements were performed in complete aqueous media (LOD=0.38 µM). Myco-F enables detection of fluoride ions in living HEK293 cells and localizes in the eye region (among other regions) of the zebrafish. DFT calculations support the proposed ESIPT working photomechanism.

Highly sensitive and rapid detection of hypochlorous acid in aqueous media and its bioimaging in live cells and zebrafish using an ESIPT-driven mycophenolic acid-based fluorescent probe.

Excessive production of potent biological oxidants such as HOCl has been implicated in numerous diseases. Thus, it is crucial to develop highly specific and precise methods to detect HOCl in living systems, preferably with molecules that can show a distinct therapeutic effect. Our study introduces the synthesis and application of a highly sensitive fluorescence "turn-on" probe, Myco-OCl, based on the mycophenolic acid scaffold with exceptional water solubility. The ESIPT-driven mechanism enables Myco-OCl to specifically and rapidly detect (<5 s) HOCl with an impressive Stokes shift of 105 nm (λex = 417 nm, λem = 522 nm) and a sub-nanomolar (97.3 nM) detection limit with the detection range of 0 to 50 µM. The potential of Myco-OCl as an excellent biosensor is evident from its successful application for live cell imaging of exogenous and endogenous HOCl. In addition, Myco-OCl enabled us to detect HOCl in a zebrafish inflammatory animal model. These underscore the great potential of Myco-OCl for detecting HOCl in diverse physiological systems. Our findings thus offer a highly promising tool for detecting HOCl in living organisms.

It goes both ways: The relationship between anxiety and mild cognitive impairment.

OBJECTIVE: To investigate the relationship between anxiety and mild cognitive impairment (MCI), and whether it is mediated by perceived stress, at the population level. METHOD AND DESIGN: In a longitudinal study of 368 adults aged 65+ from a population-based cohort, we annually assessed anxiety symptoms (GAD-7), perceived stress (PSS-4), and ratings on the Clinical Dementia Rating (CDR®), where CDR = 0.5 was operationalized as MCI. Examining data from three consecutive assessment waves, we first determined the associations between anxiety at the first wave with MCI at the third wave, and vice versa. We then used mediation analyses to determine whether the pathways in both directions were mediated by perceived stress at the second wave, adjusting for demographics and other relevant covariates. RESULTS: We confirmed significant bidirectional longitudinal associations between anxiety and MCI. Perceived stress was detected as a significant mediator for both pathways between anxiety and MCI, explaining 37.1% of the total effect (TE) of anxiety on incident MCI while conversely explaining 27.1% of the TE of MCI on anxiety. CONCLUSIONS: A bidirectional relationship with a 2-year lag between anxiety and MCI was mediated through perceived stress. Clinicians should be sensitive both to potential consequent anxiety when patients present with cognitive impairment, and to potential incipient MCI when the presenting complaint is anxiety. Managing stress may help mitigate adverse outcomes.

G-quadruplex motifs in Neisseria gonorrhoeae as anti-gonococcal targets.

Neisseria gonorrhoeae is an obligate human pathogen that causes gonorrhea and has shown a vast emergence of multidrug resistance in recent times. It is necessary to develop novel therapeutic strategies to combat this multidrug-resistant pathogen. The non-canonical stable secondary structures of nucleic acids, G-quadruplexes (GQs), are reported to regulate gene expressions in viruses, prokaryotes, and eukaryotes. Herein, we explored the whole genome of N. gonorrhoeae to mine evolutionary conserved GQ motifs. The Ng-GQs were highly enriched in the genes involved in various important biological and molecular processes of N. gonorrhoeae. Five of these GQ motifs were characterized using biophysical and biomolecular techniques. The GQ-specific ligand, BRACO-19, showed a high affinity towards these GQ motifs and stabilized them in both in vitro and in vivo conditions. The ligand showed potent anti-gonococcal activity and modulated the gene expression of the GQ-harboring genes. Strikingly, BRACO-19 also altered the biofilm formation in N. gonorrhoeae and its adhesion and invasion of the human cervical epithelial cells. In summary, the present study showed a significant role of GQ motifs in N. gonorrhoeae biology and put forward a step closer towards the search for therapeutic measures in combating the emerging antimicrobial resistance in the pathogen. KEY POINTS: •Neisseria gonorrhoeae genome is enriched in non-canonical nucleic acid structures-G-quadruplexes. •These G-quadruplexes might regulate bacterial growth, virulence, and pathogenesis. •G-quadruplex ligands inhibit biofilm formation, adhesion, and invasion of the gonococcus bacterium.

A study of post exercise hypotension in normotensive offspring of hypertensives after acute exercise.

Background & objectives: Post exercise hypotension (PEH) is a well-known entity in hypertensive and borderline hypertensive patients. Since the results are inconsistent in normotensives and there is a genetic predisposition of the individuals to hypertension, we hypothesized that PEH is expected to occur in those normotensives who are offspring of hypertensive parents. In this study, we therefore aimed to compare the magnitude of PEH after an acute bout of moderate intensity continuous exercise (MICE) in the offspring of hypertensives vs. offspring of normotensives. Methods: Sixty normotensive participants of both genders (male and female in equal proportion), aged 18-40 yr, were divided into two groups based on their family history of hypertension. The cases (Group 1, n=30) consisted of the normotensives who were offspring of hypertensive parents while the normotensives who were offspring of normotensive parents were taken as the controls (Group 2, n=30). The hypertensive patients were excluded from the study. The individuals underwent a control session (sitting at rest for 5-10 min), followed by a single acute bout of MICE based on the target heart rate (60-70% of maximum heart rate) on a treadmill at the same time of the day (in the morning). The pre- and post-exercise measurements (after 10 min post exercise) of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) were taken in all the participants using mercury sphygmomanometer in sitting position on the left arm. The intergroup and intragroup net effects of exercise on BP were compared with P<0.05 considered significant. Results: The mean SBP was reduced by 5 mmHg than the baseline in the offspring of hypertensives (cases) as compared to the controls after exercise (P=0.01). The fall in mean DBP and MAP was insignificant across both the groups, but the magnitude of PEH measured as delta changes (BP before and after exercise) in SBP (~5 mmHg) and MAP (~4 mmHg) were significantly higher for the cases as compared to the controls (P=0.01). Interpretation & conclusions: PEH occurs in higher magnitude in normotensives who are genetically predisposed to hypertension, such as offspring of hypertensive parents, and may find regular exercise-induced PEH as an important primary preventive tool to prevent or delay the development of hypertension.

Recent advancements in the expedition of microneedles: from lab worktops to diagnostic care centers.

Microneedle (MN) technology plays a significant role in bioengineering as it allows for minimally invasive exposure to the skin via the non-invasive procedure, increased drug permeability, and improved biological molecule detectability in the epidermal layers, all while improving therapeutic safety and effectiveness. However, MNs have several significant drawbacks, including difficulty scaling up, variability in drug delivery pattern regarding the skin's external environment, blockage of dermal tissues, induction of inflammatory response at the administration site, and limitation of dosing based on the molecular weight of drug and size. Despite these drawbacks, MNs have emerged as a special transdermal theranostics instrument in clinical research to assess physiological parameters. Bioimaging technology relies on microneedles that can measure particular analytes in the extracellular fluid effectively by crossing the stratum corneum, making them "a unique tool in diagnostics detection and therapeutic application inside the body." This review article discusses the recent advances in the applications especially related to the diagnostics and toxicity challenges of microneedles. In addition, this review article discusses the clinical state and commercial accessibility of microneedle technology-based devices in order to provide new information to scientists and researchers.

Recent Update on Nanoemulsion Impregnated Hydrogel: a Gleam into the Revolutionary Strategy for Diffusion-Controlled Delivery of Therapeutics.

Since earlier times, dermatological remedies have been utilized to treat diseases associated with pain, irritation, and skin conditions. Compared to other routes of drug delivery, topical delivery of drugs offers several benefits. Scientists are investigating different alterations in dosage forms in addition to existing topical formulations such as ointments, gels, creams, lotions, and ointments to significantly improve the permeation of drugs and enhance the pharmacological efficacy of medications that are poorly absorbed via the skin. Conventional formulations have a plethora of problems viz. poor absorption, no target specificity, low spreadability, and inadequate bioavailability which leads the researchers toward developing novel formulations like nanoemulsions. The nanoemulsion can enhance the gradient in concentration and thermodynamic movement toward the epidermis and enhance the penetration of its constituents. However, due to its difficult application, nanoemulsion's lower viscosity limited its use in transdermal delivery. Thus, the development of nanoemulsion-based hydrogels has shown to be a successful strategy for removing obstacles from existing drug formulations. The simple application, expedient spreadability, non-stickiness, safety, and effectiveness of nanoemulsion-based hydrogel have led to substantial growth in their research in recent years. This review gives a brief idea about the prevalence of skin diseases, skin as an obstacle for drug delivery, and recent research insights to combat these obstacles. The work highlights the mechanism of drug release via nanoemulsion, hydrogels, and nanoemulsion-based hydrogels with reference to recent research on hydrophobic and hydrophilic drugs.

Nano vs Resistant Tuberculosis: Taking the Lung Route.

Tuberculosis (TB) is among the top 10 infectious diseases worldwide. It is categorized among the leading killer diseases that are the reason for the death of millions of people globally. Although a standardized treatment regimen is available, non-adherence to treatment has increased multi-drug resistance (MDR) and extensive drug-resistant (XDR) TB development. Another challenge is targeting the death of TB reservoirs in the alveoli via conventional treatment. TB Drug resistance may emerge as a futuristic restraint of TB with the scarcity of effective Anti-tubercular drugs. The paradigm change towards nano-targeted drug delivery systems is mostly due to the absence of effective therapy and increased TB infection recurrent episodes with MDR. The emerging field of nanotechnology gave an admirable opportunity to combat MDR and XDR via accurate diagnosis with effective treatment. The new strategies targeting the lung via the pulmonary route may overcome the new incidence of MDR and enhance patient compliance. Therefore, this review highlights the importance and recent research on pulmonary drug delivery with nanotechnology along with prevalence, the need for the development of nanotechnology, beneficial aspects of nanomedicine, safety concerns of nanocarriers, and clinical studies.