Factors Associated With Delayed Gastric Emptying in Symptomatic Diabetic and Non-diabetic Patients: A Retrospective Observational Study.

Background Gastroparesis, characterized by delayed gastric emptying without mechanical obstruction, is a significant complication, especially in diabetic individuals. It manifests through symptoms such as abdominal bloating, feelings of fullness, and pain. This study investigates the prevalence of gastroparesis among non-diabetic and diabetic patients, exploring associations with demographic data, hemoglobin A1C (HbA1C) levels, and symptoms. Methodology This retrospective, observational, cohort study included patients with gastroparesis symptoms who underwent a nuclear gastric emptying study from January 2021 to April 2023. The study analyzed demographic data, symptoms, and HbA1c levels to identify correlations with delayed gastric emptying. Results Of 157 patients, 34.4% exhibited delayed gastric emptying. Diabetic patients comprised 29.3% of the sample, with a notable disease duration of over 10 years in 77.3% of cases. Symptoms such as nausea, vomiting, epigastric pain, and early satiety were prevalent, with significant associations between delayed emptying and female gender, higher HbA1c, and vomiting. Conclusions Delayed gastric emptying is significantly associated with female gender, elevated HbA1c levels, and when vomiting is the presenting symptom. Highlighting the importance of awareness among healthcare providers and the community, the findings encourage collaborative efforts for further gastroparesis research to better understand the predictive factors and mechanisms.

Design of load-aware resource allocation for heterogeneous fog computing systems.

The execution of delay-aware applications can be effectively handled by various computing paradigms, including the fog computing, edge computing, and cloudlets. Cloud computing offers services in a centralized way through a cloud server. On the contrary, the fog computing paradigm offers services in a dispersed manner providing services and computational facilities near the end devices. Due to the distributed provision of resources by the fog paradigm, this architecture is suitable for large-scale implementation of applications. Furthermore, fog computing offers a reduction in delay and network load as compared to cloud architecture. Resource distribution and load balancing are always important tasks in deploying efficient systems. In this research, we have proposed heuristic-based approach that achieves a reduction in network consumption and delays by efficiently utilizing fog resources according to the load generated by the clusters of edge nodes. The proposed algorithm considers the magnitude of data produced at the edge clusters while allocating the fog resources. The results of the evaluations performed on different scales confirm the efficacy of the proposed approach in achieving optimal performance.

A Case Report of a Cold Chest Wall Abscess Following Bacillus Calmette-Guérin Vaccination.

The Bacillus Calmette-Guérin (BCG) vaccine, a cornerstone in global immunization programs for tuberculosis prevention, has generally proven to be safe and effective. However, rare complications, including localized abscess formation, have been reported. This case report highlights a two-year-old male who developed a painless swelling on the left chest wall, noticed six weeks post-BCG vaccination. Physical and imaging evaluations confirmed a cold abscess. Laboratory tests ruled out alternative diagnoses. Antitubercular therapy led to a favorable response, avoiding surgical intervention. Follow-up revealed complete resolution, showcasing successful management of this rare BCG-related complication in a pediatric patient. The success of antimycobacterial therapy supports a tailored and conservative approach, raising questions about the necessity of surgical intervention. The presented case sheds light on the complex interplay between BCG vaccination, host response, and rare complications, providing valuable insights for further research. Vigilance, robust surveillance, and collaborative efforts are essential to unravel vaccine-related adverse events. This case contributes to a deeper understanding of rare BCG-related complications, guiding clinical practice, and advancing the knowledge base.

A Combined Experimental and Computational Study of Novel Benzotriazinone Carboxamides as Alpha-Glucosidase Inhibitors.

Diabetes is a chronic metabolic disorder of the endocrine system characterized by persistent hyperglycemia appears due to the deficiency or ineffective use of insulin. The glucose level of diabetic patients increases after every meal and medically recommended drugs are used to control hyperglycemia. Alpha-glucosidase inhibitors are used as antidiabetic medicine to delay the hydrolysis of complex carbohydrates. Acarbose, miglitol, and voglibose are commercial drugs but patients suffer side effects of flatulence, bloating, diarrhea, and loss of hunger. To explore a new antidiabetic drug, a series of benzotriazinone carboxamides was synthesized and their alpha-glucosidase inhibition potentials were measured using in vitro experiments. The compounds 14k and 14l were found to be strong inhibitors compared to the standard drug acarbose with IC50 values of 27.13 ± 0.12 and 32.14 ± 0.11 µM, respectively. In silico study of 14k and 14l was carried out using molecular docking to identify the type of interactions developed between these compounds and enzyme sites. Both potent compounds 14k and 14l exhibited effective docking scores by making their interactions with selected amino acid residues. Chemical hardness and orbital energy gap values were investigated using DFT studies and results depicted affinity of 14k and 14l towards biological molecules. All computational findings were found to be in good agreement with in vitro results.

Template-assisted synthesis of molecularly imprinted polymers for the removal of methyl red from aqueous media.

This study entails the synthesis of molecularly imprinted polymers (MIPs) with good selectivity coefficients for azo dye as a potential sorbent material to extract azo dye from polluted aqueous media. A series of MIPs for methyl red (MR) as a template, were synthesized by changing the molar ratio of functional monomers, via precipitation polymerization format of non-covalent approach. Water-soluble functional monomer; acrylic acid (AA) was used to weave the frame work of polymers while ethylene glycol dimethacrylate (EGDMA) was utilized as crosslinking monomer. The impact of different experimental parameters, such as mole ratio of monomer (functional) to crosslinking monomer on the molecular recognition was investigated. The highly efficient and selective MR-MIP was used for the removal of spiked MR dye from different water samples. The selected imprinted polymer, MR1-MIP was able to selectively remove the MR molecules from aqueous media. A significant amount of dye was removed by MR1-MIP from the river water samples with a high degree of removal efficiency i.e. 92.25%. The imprinting factor of 3.75 for MR1-MIP indicated that the high selectivity in terms of adsorption for MR. A minimum loss of only ~ 3.35% in the removal efficiency within ten sequential cycles of adsorption-desorption study evidenced that MR-MIPs could be used as the most cost effective and best sorbent for the removal of MR from polluted water. Furthermore, the structural properties of MR-MIPs were characterized by FTIR and EDX, whereas TGA, SEM and BET were used to describe the thermal, morphological and surface structures of the particles, respectively.

Optimized serum ferritin prediction of iron overload in transfusion-dependent thalassemia: likelihood ratio and age-adjustment approach.

BACKGROUND: Early detection of iron overload in transfusion-dependent thalassemia (TDT) patients is critical to prevent complications and improve survival. OBJECTIVES: Evaluate the utility of serum ferritin (SF) in the prediction of hepatic and myocardial iron overload (HIO and MIO) compared to T2*-MRI. DESIGN: Retrospective SETTINGS: Governmental hospitals. PATIENTS AND METHODS: Patients with TDT who had T2*-MRI examinations between January 2016 to October 2019 were included. The predictive value of SF for detection of HIO and MIO was assessed by measuring area under the curve (AUC). A sample size of 123 cases was calculated to detect a correlation of 0.25 with 90% power and a two-sided type I error of 0.05. MAIN OUTCOME MEASURES: The correlation between SF and estimated hepatic iron concentration. SAMPLE SIZE: 137 TDT patients who required regular blood transfusions. RESULTS: The predictive value of SF was excellent for detection of HIO (AUC=0.83-0.87) but fair for detection of MIO (AUC=0.67). The two independent predictors of MIO were age and SF. The log of (age × SF) enhanced the SF predictive value for MIO (AUC=0.78). SF values of 700 and 1250 mg/L effectively excluded mild and moderate HIO with a sensitivity of 97.8% and 94.2%, respectively (LR-=0.1). While SF values of 1640 and 2150 mg/L accurately diagnosed mild and moderate HIO with a specificity of 95.55% and 96.4%, respectively (LR+>10). A log of (age × SF) cut-off value of 4.15 effectively excluded MIO (LR-=0.1), while a value of 4.65 moderately confirmed MIO (LR+=3.2). CONCLUSIONS: SF is an excellent predictor of hepatic IO in TDT. Age adjustment enhanced its myocardial IO predictive accuracy. Likelihood ratio-based SF cut-off values may help clinicians in risk stratification and treatment decision-making. LIMITATIONS: The laboratory data were gathered retrospectively and although the risk of selection bias for T2*-MRI examination is thought to be low, it cannot be ignored. CONFLICT OF INTEREST: None.

Review on Propolis Applications in Food Preservation and Active Packaging.

Propolis is a natural hive product collected by honeybees from different plants and trees. The collected resins are then mixed with bee wax and secretions. Propolis has a long history of use in traditional and alternative medicine. Propolis possesses recognized antimicrobial and antioxidant properties. Both properties are characteristics of food preservatives. Moreover, most propolis components, in particular flavonoids and phenolic acids, are natural constituents of food. Several studies suggest that propolis could find use as a natural food preservative. This review is focused on the potential application of propolis in the antimicrobial and antioxidant preservation of food and its possible application as new, safe, natural, and multifunctional material in food packaging. In addition, the possible influence of propolis and its used extracts on the sensory properties of food is also discussed.

Superior Mediastinal Syndrome Misdiagnosed as Foreign Body Aspiration: A Case Report.

Superior mediastinal syndrome is a life-threatening pediatric oncological emergency that requires high level of awareness and clinical suspicion to avoid misdiagnosis and devastating outcomes. Early diagnostic evaluation and management of underlying etiology are of utmost significance for optimal results. In children, it is most commonly caused by non-Hodgkin's lymphoma and T-cell lymphoblastic leukemia. We report a case of a six-year-old boy with superior mediastinal syndrome secondary to T-cell acute lymphoblastic leukemia, initially misdiagnosed as foreign body aspiration and underwent a procedure with a life-threatening outcome.

Predicting Severe COVID-19 Infection on Initial Diagnosis: Comparison and Validation of CT Imaging Triage Tools.

BACKGROUND: Developing a reliable predictive tool of disease severity in COVID-19 infection is important to help triage patients and ensure the appropriate utilization of health-care resources. OBJECTIVE: To develop, validate, and compare three CT scoring systems (CTSS) to predict severe disease on initial diagnosis of COVID-19 infection. METHODS: One hundred and twenty and 80 symptomatic adults with confirmed COVID-19 infection who presented to emergency department were evaluated retrospectively in the primary and validation groups, respectively. All patients had non-contrast CT chest within 48 hours of admission. Three lobarbased CTSS were assessed and compared. The simple lobar system was based on the extent of pulmonary infiltration. Attenuation corrected lobar system (ACL) assigned further weighting factor based on attenuation of pulmonary infiltrates. Attenuation and volume-corrected lobar system incorporated further weighting factor based on proportional lobar volume. The total CT severity score (TSS) was calculated by adding individual lobar scores. The disease severity assessment was based on Chinese National Health Commission guidelines. Disease severity discrimination was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: The ACL CTSS demonstrated the best predictive and consistent accuracy of disease severity with an AUC of 0.93(95%CI:0.88-0.97) in the primary cohort and 0.97 (95%CI:0.91.5-1) in the validation group. Applying a TSS cut-off value of 9.25, the sensitivities were 96.4% and 100% and the specificities were 75% and 91% in the primary and validation groups, respectively. CONCLUSION: The ACL CTSS showed the highest accuracy and consistency in predicting severe disease on initial diagnosis of COVID-19. This scoring system may provide frontline physicians with a triage tool to guide admission, discharge, and early detection of severe illness.

Antimicrobial Potential of Pithecellobium dulce Seed Extract against Pathogenic Bacteria: In Silico and In Vitro Evaluation.

Clinical multi-drug-resistant bacteria continue to be a serious health problem. Plant-derived molecules are an important source of bioactive compounds to counteract these pathogenic bacteria. In this paper, we studied the chemical composition of the methanol (80%) extract from Pithecellobium dulce seed (Hail, Saudi Arabia) and its ability to inhibit the growth of clinically relevant multi-drug-resistant bacteria. Molecular docking analysis was performed to predict the best compounds with low binding energy and high affinity to interact with two Staphylococcus aureus receptors. Data showed that P. dulce extract is a rich source of D-turanose (55.82%), hexadecanoic acid (11.56%), indole-1-acetic acid (11.42%), inositol (5.78%), and octadecanoic acid (4.36%). The obtained extract showed antibacterial activity towards tested clinical bacterial strains with MIC values ranging from 233 mg/mL for Acinetobacter baumannii to 300 mg/mL for S. aureus and Escherichia coli. Turanose interaction has resulted in -7.4 and -6.6 kcal/mol for 1JIJ and 2XCT macromolecules, while inositol showed energy values (-7.2 and -5.4 kcal/mol) for the same receptors. Multiple identified compounds showed desirable bioavailability properties indicating its great potential therapeutic use in human. Overall, current investigation highlights the possible use of P. dulce extract as a valuable source for drug development against pathogenic drug-resistant bacteria.

Metal organic frameworks as promising sensing tools for electrochemical detection of persistent heavy metal ions from water matrices: A concise review.

Water bodies are being polluted rapidly by disposal of toxic chemicals with their huge entrance into drinking water supply chain. Among these pollutants, heavy metal ions (HMIs) are the most challenging one due to their non-biodegradability, toxicity, and ability to biologically hoard in ecological systems, thus posing a foremost danger to human health. This can be addressed by robust, sensitive, selective, and reliable sensing of metal ions which can be achieved by Metal organic frameworks (MOF) based electrochemical sensors. In the present era, MOFs have caught greater interest in a variety of applications including sensing of hazardous pollutants such as heavy metal ions. So, in this review article, types, synthesis and working mechanism of MOF based sensors is explained to give general overview with updated literature. First time, detailed study is done for sensing of metal ions such as chromium, mercury, zinc, copper, manganese, palladium, lead, iron, cadmium and lanthanide by MOFs based electrochemical sensors. The use of MOFs as electrochemical sensors has attractive success story along with some challenges of the area. Considering these challenges, we attempted to highlight the milestone achieved and shortcomings along with future prospective of the MOFs for employing it in electrochemical sensing devices for HMIs. Finally, challenges and future prospects have been discussed to promote the development of MOFs-based sensors in future.

Natural Products/Bioactive Compounds as a Source of Anticancer Drugs.

Cancer is one of the major deadly diseases globally. The alarming rise in the mortality rate due to this disease attracks attention towards discovering potent anticancer agents to overcome its mortality rate. The discovery of novel and effective anticancer agents from natural sources has been the main point of interest in pharmaceutical research because of attractive natural therapeutic agents with an immense chemical diversity in species of animals, plants, and microorganisms. More than 60% of contemporary anticancer drugs, in one form or another, have originated from natural sources. Plants and microbial species are chosen based on their composition, ecology, phytochemical, and ethnopharmacological properties. Plants and their derivatives have played a significant role in producing effective anticancer agents. Some plant derivatives include vincristine, vinblastine, irinotecan, topotecan, etoposide, podophyllotoxin, and paclitaxel. Based on their particular activity, a number of other plant-derived bioactive compounds are in the clinical development phase against cancer, such as gimatecan, elomotecan, etc. Additionally, the conjugation of natural compounds with anti-cancerous drugs, or some polymeric carriers particularly targeted to epitopes on the site of interest to tumors, can generate effective targeted treatment therapies. Cognizance from such pharmaceutical research studies would yield alternative drug development strategies through natural sources which could be economical, more reliable, and safe to use.

Natural Strategies as Potential Weapons against Bacterial Biofilms.

Microbial biofilm is an aggregation of microbial species that are either attached to surfaces or organized into an extracellular matrix. Microbes in the form of biofilms are highly resistant to several antimicrobials compared to planktonic microbial cells. Their resistance developing ability is one of the major root causes of antibiotic resistance in health sectors. Therefore, effective antibiofilm compounds are required to treat biofilm-associated health issues. The awareness of biofilm properties, formation, and resistance mechanisms facilitate researchers to design and develop combating strategies. This review highlights biofilm formation, composition, major stability parameters, resistance mechanisms, pathogenicity, combating strategies, and effective biofilm-controlling compounds. The naturally derived products, particularly plants, have demonstrated significant medicinal properties, producing them a practical approach for controlling biofilm-producing microbes. Despite providing effective antibiofilm activities, the plant-derived antimicrobial compounds may face the limitations of less bioavailability and low concentration of bioactive molecules. The microbes-derived and the phytonanotechnology-based antibiofilm compounds are emerging as an effective approach to inhibit and eliminate the biofilm-producing microbes.

General Nutritional Profile of Bee Products and Their Potential Antiviral Properties against Mammalian Viruses.

Bee products have been extensively employed in traditional therapeutic practices to treat several diseases and microbial infections. Numerous bioactive components of bee products have exhibited several antibacterial, antifungal, antiviral, anticancer, antiprotozoal, hepatoprotective, and immunomodulatory properties. Apitherapy is a form of alternative medicine that uses the bioactive properties of bee products to prevent and/or treat different diseases. This review aims to provide an elaborated vision of the antiviral activities of bee products with recent advances in research. Since ancient times, bee products have been well known for their several medicinal properties. The antiviral and immunomodulatory effects of bee products and their bioactive components are emerging as a promising alternative therapy against several viral infections. Numerous studies have been performed, but many clinical trials should be conducted to evaluate the potential of apitherapy against pathogenic viruses. In that direction, here, we review and highlight the potential roles of bee products as apitherapeutics in combating numerous viral infections. Available studies validate the effectiveness of bee products in virus inhibition. With such significant antiviral potential, bee products and their bioactive components/extracts can be effectively employed as an alternative strategy to improve human health from individual to communal levels as well.

An Overview of Biofilm Formation-Combating Strategies and Mechanisms of Action of Antibiofilm Agents.

Biofilm formation on surfaces via microbial colonization causes infections and has become a major health issue globally. The biofilm lifestyle provides resistance to environmental stresses and antimicrobial therapies. Biofilms can cause several chronic conditions, and effective treatment has become a challenge due to increased antimicrobial resistance. Antibiotics available for treating biofilm-associated infections are generally not very effective and require high doses that may cause toxicity in the host. Therefore, it is essential to study and develop efficient anti-biofilm strategies that can significantly reduce the rate of biofilm-associated healthcare problems. In this context, some effective combating strategies with potential anti-biofilm agents, including plant extracts, peptides, enzymes, lantibiotics, chelating agents, biosurfactants, polysaccharides, organic, inorganic, and metal nanoparticles, etc., have been reviewed to overcome biofilm-associated healthcare problems. From their extensive literature survey, it can be concluded that these molecules with considerable structural alterations might be applied to the treatment of biofilm-associated infections, by evaluating their significant delivery to the target site of the host. To design effective anti-biofilm molecules, it must be assured that the minimum inhibitory concentrations of these anti-biofilm compounds can eradicate biofilm-associated infections without causing toxic effects at a significant rate.

Nicotine and cotinine quantification after a 4-week inhalation of electronic cigarette vapors in male and female mice using UPLC-MS/MS.

OBJECTIVES: To detect the cotinine and nicotine serum concentrations of female and male C57BL/6J mice after a 4-week exposure to electronic (e)-cigarette vapors using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). METHODS: This experimental study was carried out at an animal facility and laboratories, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, between January and August 2020. A 4-week exposure to e-cigarettes was carried out using male and female mice and serum samples were obtained for cotinine and nicotine quantification using UPLC-MS/MS. The chromatographic procedures involved the use of a BEH HSS T3 C18 column (100 mm x 2.1 mm, 1.7 µm) with acetonitrile as a mobile phase and 0.1% formic acid (2:98 v/v). RESULTS: The applied methodology has highly efficient properties of detection, estimation, and extraction, where the limit of quantification (LOQ) for nicotine was 0.57 ng/mL and limit of detection (LOD) for nicotine was 0.19 ng/mL, while the LOQ for cotinine was 1.11 ng/mL and LOD for cotinine was 0.38 ng/mL. The correlation coefficient was r2>0.99 for both compounds. The average recovery rate was 101.6±1.33 for nicotine and 100.4±0.54 for cotinine, while the precision and accuracy for cotinine and nicotine were less than 6.1. The serum cotinine level was higher in males (433.7±19.55) than females (362.3±16.27). CONCLUSION: This study showed that the gender factor might play a crucial role in nicotine metabolism.

Strengthening the Bridge Between Academic and the Industry Through the Academia-Industry Collaboration Plan Design Model.

The study has been undertaken to integrate two different aspects of the triple helix model: universities and the industry. Special attention has been paid to the prevailing difference between the two, hampering their working as a coherent unit. Integrating the existing knowledge in the study, we proposed the Academia-Industry Collaboration Plan (AICP) design model. The model comprises processes, methods or approaches, and tools. Processes serve as a road map to third parties for establishing collaboration between academia and the industry. It has all the essential process models and a series of steps that help minimize the organizational complexity of the collaboration process between academia and the industry. Methods or approaches serve the purpose of implementing those processes effectively. Finally, appropriate tools are selected to integrate possible collaboration improvements that lead to innovation.

Dual Inhibition of Phosphodiesterase and Ca++ Channels Explains the Medicinal Use of Balanites aegyptiaca (L.) in Hyperactive Gut Disorders.

The present study attempted to evaluate and rationalize the medicinal use of the methanolic extract of the fruits of Balanites aegyptiaca (B. aegyptiaca) in the treatment of hyperactive gut disorders. The in vivo, castor oil-induced diarrhea model in mice was followed to test its antidiarrheal effect. To test the antispasmodic effect and to explore its pharmacodynamic details, isolated small intestines (ileum) obtained from rats were selected to provide physiological conditions for the ex vivo assays. In the in vivo assays, the orally administered extract of B. aegyptiaca protected mice from diarrheal drops with resultant percent inhibitions of 40% and 80% at the respective doses of 200 mg/kg and 400 mg/kg, while the highest protection (100%) was observed with a positive control drug, loperamide, at 10 mg/kg. In the ileum, B. aegyptiaca produced an antispasmodic effect in a concentration-dependent manner by inhibiting the carbachol (CCh; 1 µM) and high K+ (80 mM)-evoked spasms with resultant EC50 values of 1.44 mg/mL (1.08-1.78) and 1.27 mg/mL (0.98-1.66), respectively. Papaverine, a known phosphodiesterase enzyme (PDE) inhibitor and blocker of Ca++ channels (CCB), also inhibited both CCh and high K+ induced contractions at comparable EC50 values of 8.72 µM (7.92-9.24) and 8.14 µM (7.62-8.84), respectively. Contrary to the extract and papaverine, verapamil showed distinctly higher potency in regard to inhibiting high K+, compared to CCh-evoked spasms that had EC50 values of 0.16 µM (0.13-0.261) and 2.54 µM (2.28-2.92), respectively. The inhibitory effects of B. aegyptiaca on PDE were further confirmed when the pre-incubated extract shifted the isoprenaline-mediated relaxation curves (CRCs) towards the left, similar to papaverine, whereas the CCB-like effect was confirmed when the pre-incubated tissues with B. aegyptiaca caused deflection in the Ca++ CRCs towards the right, constructed in Ca++ free medium with suppression of the maximum response. Thus, this study provides detailed, mechanistic support for the medicinal use of B. aegyptiaca in the treatment of hyperactive gut disorders.

Immune-related therapeutics: an update on antiviral drugs and vaccines to tackle the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic rapidly spread globally. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19, is a positive-sense single-stranded RNA virus with a reported fatality rate ranging from 1% to 7%, and people with immune-compromised conditions, children, and older adults are particularly vulnerable. Respiratory failure and cytokine storm-induced multiple organ failure are the major causes of death. This article highlights the innate and adaptive immune mechanisms of host cells activated in response to SARS-CoV-2 infection and possible therapeutic approaches against COVID-19. Some potential drugs proven to be effective for other viral diseases are under clinical trials now for use against COVID-19. Examples include inhibitors of RNA-dependent RNA polymerase (remdesivir, favipiravir, ribavirin), viral protein synthesis (ivermectin, lopinavir/ ritonavir), and fusion of the viral membrane with host cells (chloroquine, hydroxychloroquine, nitazoxanide, and umifenovir). This article also presents the intellectual groundwork for the ongoing development of vaccines in preclinical and clinical trials, explaining potential candidates (live attenuated-whole virus vaccines, inactivated vaccines, subunit vaccines, DNAbased vaccines, protein-based vaccines, nanoparticle-based vaccines, virus-like particles and mRNA-based vaccines). Designing and developing an effective vaccine (both prophylactic and therapeutic) would be a long-term solution and the most effective way to eliminate the COVID-19 pandemic.

Enhanced Antifungal and Wound Healing Efficacy of Statistically Optimized, Physicochemically Evaluated Econazole-Triamcinolone Loaded Silica Nanoparticles.

Co-encapsulated econazole nitrate-triamcinolone acetonide loaded biocompatible, physically stable, and non-irritating mesoporous silica nanoparticles (EN-TA-loaded MSNs) were prepared and optimized by using a central composite rotatable design (CCRD) for providing better therapeutic efficacy against commonly prevailed resistant fungal infections. These drugs loaded MSNs can significantly overcome the deficiencies and problems like short duration of action, requirement of frequent administration, erythema, and burning sensation and irritation associated with conventional drug delivery systems. The stability of optimized drugs loaded MSNs prepared with 100 gm of oil at pH 5.6 with a stirring time of 2 h was confirmed from a zeta potential value of -25 mV. The remarkable compatibility of formulation ingredients was depicted by X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR) spectra while scanning electron microscopy (SEM) and size analysis represented a very fine size distribution of nanoparticles ranging from 450-600 nm. The CCRD clearly predicted that the optimized parameters of drugs loaded MSNs have better values of percentage yield (85%), EN release (68%), and TA release (70%). Compared to pure drugs, the decreased cytotoxicity of EN-TA-loaded MSNs was quite evident because they showed a cell survival rate of 90%, while in the case of pure drugs, the survival rate was 85%. During in vivo antifungal testing against Candida albicans performed on three different groups, each consisting of six rabbits, the EN-TA-loaded MSNs were relatively superior in eradicating the fungal infection as a single animal exhibited a positive culture test. Rapid recovery of fungal infection and a better therapeutic effect of EN-TA-loaded MSN were quite evident in wound healing and histopathology studies. Likewise, on the 14th day, a larger inhibitory zone was measured for optimized nanoparticles (15.90 mm) compared to the suspension of pure drugs (13.90 mm). In skin irritation studies, MSNs did not show a grade of erythema compared to pure drugs, which showed a four-fold grade of erythema. As a result, MSNs loaded with combination therapy seem to have the potential of improving patient compliance and tolerability by providing enhanced synergistic antifungal effectiveness at a reduced dose with accelerated wound healing and reduced toxicity of therapeutics.