Application of carboxymethylcellulose in combination with essential oils nano-emulsions edible coating for the preservation of kiwifruit.

The present research investigates the effectiveness of nano-emulsified coatings (C-1, C-2, and C-3) in preserving the kiwifruit at a temperature of 10 ± 2 °C with 90-95 % relative humidity (RH) for 30 days. The nano-emulsions were prepared from varied carboxymethyl cellulose (CMC) concentrations with different combinations of essential oils such as thyme, clove, and cardamom. Dynamic light scattering investigation with Zeta Sizer revealed that C-1, C-2, and C-3 nano-emulsions have nano sizes of 81.3 ± 2.3, 115.3 ± 4.2, and 63.2 ± 3.2 nm, respectively. The scanning electron microscopy images showed that the nanoemulsion of C-1 had homogenous spherical globules, C-2 had voids, and C-3 showed a non-porous structure with uniform dispersion. The X-ray diffraction analysis indicated that C-1, C-2, and C-3 nano-emulsion exhibited distinct crystallinity and peaks. The nano-emulsion C-1 had reduced crystallinity, while C-2 had lower intensity peaks, and C-3 had increased crystallinity. The results documented that compared to control kiwifruit samples, the samples coated with C-3 nano-emulsion have decreased weight loss, decay incidence, soluble solids, maturity index activity, ethylene production, total bacterial count, and increased titratable acid, and firmness attributes. The results of current research are promising and would be applicable in utilization in industrial applications.

Multi-gene panel sequencing in highly consanguineous families and patients with congenital forms of skeletal dysplasias.

Skeletal dysplasias (SKDs) are a heterogeneous group of more than 750 genetic disorders characterized by abnormal development, growth, and maintenance of bones or cartilage in the human skeleton. SKDs are often caused by variants in early patterning genes and in many cases part of multiple malformation syndromes and occur in combination with non-skeletal phenotypes. The aim of this study was to investigate the underlying genetic cause of congenital SKDs in highly consanguineous Pakistani families, as well as in sporadic and familial SKD cases from India using multigene panel sequencing analysis. Therefore, we performed panel sequencing of 386 bone-related genes in 7 highly consanguineous families from Pakistan and 27 cases from India affected with SKDs. In the highly consanguineous families, we were able to identify the underlying genetic cause in five out of seven families, resulting in a diagnostic yield of 71%. Whereas, in the sporadic and familial SKD cases, we identified 12 causative variants, corresponding to a diagnostic yield of 44%. The genetic heterogeneity in our cohorts was very high and we were able to detect various types of variants, including missense, nonsense, and frameshift variants, across multiple genes known to cause different types of SKDs. In conclusion, panel sequencing proved to be a highly effective way to decipher the genetic basis of SKDs in highly consanguineous families as well as sporadic and or familial cases from South Asia. Furthermore, our findings expand the allelic spectrum of skeletal dysplasias.

5-Fluorouracil-Loaded Hyaluronic Acid-Coated Niosomal Vesicles: Fabrication and Ex Vivo Evaluation for Skin Drug Delivery.

5-Fluorouracil (5-FU) is one of the most potent drugs against solid tumors. However, its parenteral administration is associated with systemic toxicity, while its topical application has limited percutaneous absorption. To overcome these limitations, the current study undertakes the formulation of 5-FU as niosomal vesicles that were coated with hyaluronic acid to improve its targeting efficiency for cancer cells. The niosomes were prepared by the thin-film hydration method using cholesterol as physiological lipid and nonionic surfactants (Tween 80 and Span 80) in the ratio of 1:1. The niosomal vesicles were characterized for their size, size distribution, viscosity, surface tension, density, and drug entrapment efficiency. The vesicles were within the particle size range of 337-478 nm with relatively homogeneous particle size distribution (PDI ≤ 0.5). The ζ-potential and drug entrapment efficiency of coated formulations (F2 and F4) were comparatively higher than corresponding noncoated formulations (F1 and F3). The release behavior of 5-FU from niosomal vesicles using a dialysis membrane depicts that initial burst drug release was higher for F1 and F3 due to their smaller particle size in comparison to their coated counterparts. However, the release was more controlled for F4 due to the larger particle size, higher viscosity, and entrapped fraction of the formulation. The permeation of the drug through the rat's skin was comparatively higher in the case of noncoated formulations than their coated counterparts (p ≤ 0.05). This could be attributed to their small particle size and lower surface tension. In the case of coated formulations, the hydrophilic hyaluronic acid hinders the permeation of the drug through the lipid bilayer membrane of the skin. The retention of the drug in the skin was found to be in the range of 20-40%, which is sufficient to achieve optimum drug concentration in the tumorous tissue. Overall, the study successfully designed novel niosomal carrier systems for improved 5-FU delivery after topical application.

The Problem of Occult Pyelonephritis: Acute Pyelonephritis in Patients Presenting Only with Lower Urinary Tract Symptoms.

Pyelonephritis is a prevalent diagnosis of emergency department visits. It commonly presents as flank pain and costovertebral tenderness with urinary symptoms. However, some cases occur without typical symptoms. Our study highlights the dubious presentation of pyelonephritis with lower urinary tract symptoms (LUTS) only. This study was conducted at a tertiary care hospital, where charts and files were reviewed from January 11, 2018 to February 28, 2019 for all the patients with a diagnosis of acute pyelonephritis from medical records. In our study, 521 patients were included and 492 (94%) of the participants were suffering from pyelonephritis. Approximately 22.8% of the patients showed the absence of both flank pain and costovertebral tenderness but were diagnosed with pyelonephritis based on computed tomography (CT) and magnetic resonance imaging (MRI). Moreover, 27% of the patients reported upper urinary tract symptoms only and were diagnosed by CT or MRI findings. Out of that only 24% and 16% of the patients reported flank pain and costovertebral tenderness, respectively. Insignificant associations with pyelonephritis were found for age, gender and other comorbidities. Our study showed a significant number of patients with pyelonephritis without any upper urinary tract symptoms. Patients with LUTS should be evaluated further by imaging if they belong to the high-risk population.

Hyponatremia causing factors and its association with disease severity and length of stay in COVID-19 patients: A retrospective study from tertiary care hospital.

The coronavirus disease-2019 (COVID-19) infection has taken the world by storm within a few months. Evidence has suggested that patients with electrolyte imbalances at baseline may have a longer duration of hospital stay. We aimed to determine the factors associated with hyponatremia on admission in COVID-19 patients and its impact on the length of stay. We conducted a retrospective study including 521 patients who tested positive for COVID-19 and had their electrolytes checked on admission from June 2020 to October 2020. Patients with sodium <135 mmol/l were included in the hyponatremic group and were compared against normonatremic patients. The severity of COVID-19 was found to be more prevalent in the case group as compared to control (38.3% vs 29.2%; 21.1% vs 17.7%). Hyponatremic patients stayed more than 5 days in hospital (56.3% vs 46.5%), and stayed longer in special care (23.4% vs 20.0%) as compared to controls. Hyponatremic patients as compared to control were more likely to have diabetes (47.9% vs 30.0%), hypertension (49.0% vs 38.5%), ischemic heart disease (20.7% vs 15.4%), chronic liver disease (2.7% vs 1.2%), and chronic kidney disease (9.6% vs 3.8%). Upon matching on the age, the adjusted odds of hyponatremia in COVID-19-positive patients were 1.9 times among diabetic patients. Moreover, COVID-19-positive patients suffering from CKD had a higher risk of developing hyponatremia (OR = 2.3, 95% CI: 1.1-5.6). The risk of hyponatremia among COVID-19-positive patients is statistically higher in patients with 1 comorbidity (OR = 1.9, 95%CI: 1.3-3.4). Hyponatremia on admission can be used to forecast the length of hospital stay and the severity of illness in COVID-19 patients.

Sustainable appraisal of lac (Kerria Lacca) based anthraquinone natural dye for chemical and bio-mordanted viscose and silk dyeing.

The coloring behavior of laccaic acid, a natural red dye derived from lac insects, has been investigated in this work for the dyeing of silk and viscose fabrics while being heated in MW radiation. The extract was made in an aqueous and acidic media and then used to color fabrics under microwave treatment for up to 10 min. For developing new shades, eco-friendly green bio-mordants and, in comparison, chemical mordants were employed at given conditions. The obtained results revealed that the aqueous extract after 4 min of radiation exposure produced a high color strength (K/S = 17.132) onto silk and the aqueous extract after 6 min of radiation exposure produced better color strength (K/S = 6.542) onto viscose at selected conditions. The fastness ratings evaluation as per ISO standards demonstrates that bio-anchors have provided good ratings under selected irradiation and dyeing conditions. It is concluded that this environmentally friendly technique has improved the natural coloration process of fabrics as well as addition of green mordants has furnished colorfast shades using lac-derived natural anthraquinone dye.

The nexus between circular economy innovation, market competitiveness, and triple bottom lines efficiencies among SMEs: evidence from emerging economies.

Recently, the trend of circular economy innovation (CEI) drive SMEs to initiate more sustainable practices to attain market competitiveness but rare attention has been paid in emerging economies. Hence, this study plans to explore the impacts of CEI on the triple bottom lines (TBL) efficiencies in the light of market competitiveness among the production SMEs in emerging economies. The study complied data by using a survey-based technique in Pakistan, Malaysia, and China. With a sample of 306 for each segment, data were evaluated with PLS-SEM to clarify results. The findings reveal that CEI has positive significant effects on the market competitiveness and TBL efficiencies among the production SMEs in emerging economies. The findings also clarify that market competitiveness mediates the relationship between CEI and the TBL efficiencies. The findings elaborate the theoretical foundations for environmental-based production SMEs to formulate more sustainable strategies in the light of CEI to gain market competitiveness. It also clarifies the understandings of policy makers and environmental regulators by providing a novel precursor to frame the environment-based TBL guidelines for SMEs. It adds to the UN sustainability agenda by elevating the role of CEI as a novel domain among emerging economies grounded on the resource-based view theory.

Renal cortical necrosis - a rare manifestation of dengue fever: A case report.

RATIONALE: Dengue fever is a widespread mosquito-borne viral disease, most prevalent in the tropical and subtropical areas of the world. There has been a significant rise in the incidence and number of outbreaks of dengue in recent years, which has made it a matter of global concern. It may be associated with a number of renal complications, ranging from hematuria, proteinuria, glomerulonephritis, and acute tubular necrosis. However, renal cortical necrosis (RCN) is a rare renal complication of this disease. PATIENTS CONCERNS: We report the case of a young gentleman who presented with fever, vomiting, and anuria. On workup, he was found to be having complicated Dengue fever with RCN resulting in acute renal failure. DIAGNOSIS: To the best of our knowledge, RCN is not a reported renal complication of dengue fever. INTERVENTIONS AND OUTCOMES: Our report highlights the importance of early consideration of renal cortical necrosis in patients with dengue fever and persistent anuria. LESSON: This would allow for better disease prognostication while enabling physicians to develop more effective treatment strategies.

Montmorillonite modified Ni/Mg/Al ternary layered double hydroxide nanoflowers with enhanced adsorption features.

A hydrothermal technique was employed to synthesize Ni/Mg/Al ternary L.D.H.s modified with montmorillonite (NMA-MMT-LDHs). Many characterization methods, including X-ray diffraction (XRD), scanning electron microscopy (S.E.M.), Fourier transform infrared (FTIR), and Brunauer, Emmett, and Teller (B.E.T.), were used to assess the physiochemical properties of the produced analytes. Congo red and methylene blue were utilized as model dyes to treat textile waste with the synthesized analytes. The batch adsorption model was utilized to conduct the adsorption experiments under varying contact time, adsorbent dosage, and solution pH conditions. A pseudo-second-order kinetics and the Langmuir adsorption model control the adsorption process. The maximum monolayer adsorption capacities of C.R. and M.B. were determined to be 344 and 200 mg/g, respectively. As the quantity of dosage increased from the 0.01-0.04 g, the percent removal efficiency (%) increased from 75 to 87 % for S2-LDH, 84-88 % for S2-MMT, 86-93 % for S3-MMT, and 95-97% for S4-MMT for C.R. dye and 82-85 % for S2-LDH, 83-89 % for S2-MMT, 83-91 % for S3-MMT, and 84-92 % for S4-MMT for M.B. dye. The removal percentage of C.R. dye for adsorbents S2-LDH, S2-MMT, S3-MMT, and S4-MMT were 75 %, 84 %, 86 %, and 95 %, respectively and 82 %, 83 %, 83 %, and 85 %, respectively for the M.B. dye removal. The presence of MMT significantly increases the affinity of Ni/Mg/Al-LDHs (NMA-LDHs), and the designed production technique can be used to produce a variety of compositionally distinct adsorbent materials.

Investigating the nexus between authentic leadership, employees' green creativity, and psychological environment: evidence from emerging economy.

Employees' green creativity is the basic input to organizational innovation capabilities, the prime focus of practitioners to stay competitive, and a mean to solve the society's sustainable issues in dynamic markets. Hence, this study aims to evaluate the nexus between authentic leadership, psychological environment, and employees' green creativity based on the theoretical lenses of social identity and social exchange theories that have rare application in these domains. Data were collected through questionnaires from 367 operational staff members of different technical training centers of renewable energy projects in Rawalpindi and Islamabad regions at Pakistan. The findings reveal that authentic leadership is a significant precursor of employee's green creativity and self-efficacy. In addition, self-efficacy mediates while the environment of trust and safety has non-mediating role in the relationship between authentic leadership and employee's green creativity. This work brings attention to the initiatives in technical training centers for renewable energy projects and contributes to the field of employees' green creativity in the context of authentic leadership and psychological environment based on the philosophy of social identity and social exchange theories.

Porous Hierarchical Ni/Mg/Al Layered Double Hydroxide for Adsorption of Methyl Orange from Aqueous Solution.

A basic urea technique was successfully used to synthesize Mg/Al-Layered double hydroxides (Mg/Al LDHs), which were then calcined at 400 °C to form Mg/Al-Layered double oxides (Mg/Al LDOs). To reconstruct LDHs, Mg/Al LDOs were fabricated with different feeding ratios of Ni by the co-precipitation method. After synthesis, the Ni/Mg/Al-layered double hydroxides (NMA-LDHs) with 20% and 30% Ni (S1 and S2) were roasted at 400 °C and transformed into corresponding Ni/Mg/Al-layered double oxides (NMA-LDOs) (S1a and S2b, respectively). The physiochemical properties of synthesized samples were also evaluated by various characterization techniques, such as X-ray diffraction (XRD), Scanning electron microscopy (SEM), Energy dispersive X-ray spectroscopy (EDS), Fourier transform infrared (FTIR), and Brunauer, Emmett, and Teller (BET). The adsorption behavior of methyl orange (MO) onto the synthesized samples was evaluated in batch adsorption mode under varying conditions of contact time, adsorbent quantity, and solution pH. As the dosage amount increased from 0.01-0.04 g, the removal percentage of MO dye also increased from 83% to 90% for S1, 84% to 92% for S1a, 77% to 87% for S2, and 93% to 98% for S2b, respectively. For all of the samples, the adsorption kinetics were well described by the pseudo-second-order kinetic model. The equilibrium adsorption data were well fitted to both Langmuir and Freundlich models for methyl orange (MO). Finally, three adsorption-desorption cycles show that NMA-LDHs and NMA-LDOs have greater adsorption and reusability performance for MO dye, signifying that the design and fabrication strategy can facilitate the application of the natural hydrotalcite material in water remediation.

Exploring the linkage between workplace precaution measures, covid-19 fear and job performance: The moderating effect of academic competence.

The coronavirus disease 2019 (Covid-19) has created emerging mental health challenges around the world. Like other countries, Pakistan is also confronted with covid-19 calamities. The aim of the study is to examine the impacts of workplace measures (WM) on the job performance (JP) and covid-19 fears (CF) along with the moderating role of academic competence (AC) based on the organizational support theory (OST) and job demand and resources (JDR) theory. A quantitative approach was applied to collect data from 333 banking employees in Gujranwala (Pakistan), and the hypothesis were tested via structural equation modeling using SPSS and AMOS. The study findings indicate that workplace measures significantly affect covid-19 fears except for individual preventive measures (IPM). Similarly, workplace measures significantly impact on job performance apart from information about the pandemic (IAP). Moreover, academic competence insignificantly moderates between workplace measures and covid-19 fears, but a significant moderation is found between information about pandemic (IAP) and covid-19 fears. Meanwhile, academic competence significantly moderates between workplace measures and job performance instead of a relationship between information about pandemic and job performance. However, this study was limited only to the banking sector of Pakistan. So, it will open the doors for future researchers to investigate other cultural contexts and sectors. This research gives a holistic understanding of workplace measures and contributes to the body of knowledge by enlightening the moderating role of academic competence in the banking sector of Pakistan. These useful insights would enable practitioners and policy makers to develop more efficient strategies and workplace measures to enhance job performance and reduce the fears of covid-19 among employees.

Bio-fabrication of zinc oxide nanoparticles from Picea smithiana and their potential antimicrobial activities against Xanthomonas campestris pv. Vesicatoria and Ralstonia solanacearum causing bacterial leaf spot and bacterial wilt in tomato.

Due to an inevitable disadvantage of chemical or physical synthesis routes, biosynthesis approach to nanoparticles, especially metallic oxide is attractive nowadays. Metallic oxides nanoparticles present a new approach to the control of plant pathogens. ZnO nanoparticles (ZNPs) have very important role in phytopathology. In current study, biosynthesized ZNPs were tested against two devastating bacterial pathogens including Xanthomonas campestris pv. vesicatoria and Ralstonia solanacearum causing bacterial leaf spot and bacterial wilt in tomato. ZNPs were produced using a new extract from the plant Picea smithiana using an environmentally friendly, cost-effective and simple procedure. Zinc acetate was added to P. smithiana extract, stirred and heated to 200 °C. The white precipitation at the bottom were clear indication of synthesis of nanoparticles, which were further dried by subjecting them at 450 °C. X-ray diffraction pattern determined that the ZNPs had a crystallite size of about 26 nm, Fourier transform infrared spectroscopy indicated a peak between 450 and 550 cm-1 and the particle size estimated by dynamic light scattering was about 25 nm on average. Scanning electron microscopic analysis indicated that the particles were hexagonal in shape 31 nm in diameter. Antibacterial tests showed ZNPs synthesized by P. smithiana resulted in clear inhibition zones of 20.1 ± 1.5 and 18.9 ± 1.5 mm and 44.74 and 45.63% reduction in disease severity and 78.40 and 80.91% reduction in disease incidence in X. compestris pv. vesicatoria and R. solanacearum respectively at concentration of 100 µg/ml. Our findings reveal that the concentration of ZNPs was important for their efficient antibacterial activity. Overall, the biosynthesized ZNPs have been found to have effective antimicrobial activities against bacterial wilt and bacterial leaf spot in tomato.

Investigating the nexus between information technology capabilities, knowledge management, and green product innovation: evidence from SME industry.

The aim of this study to investigate the relationship between information technology capabilities (ITCs) and green product innovation (GPI). The information technology (IT) capabilities with multiple dimensions, such as IT competence, IT integration, and IT infrastructure, were used in this paper. Moreover, to verify the deep relationship between ITCs and GPI, we used knowledge management (KM) as a mediator. The data were collected through a questionnaire from the senior managers, middle-level managers, and operational staff associated with the small- and medium-sized production industry of Pakistan. We collect data in two waves between January 2022 and July 2022. The data were analyzed through the partial least square structural equation modeling through SmartPLS 3.2.2. The findings of this study conclude. First, in the direct relationship, two IT capabilities, such as IT competence and IT infrastructure, have a positive and significant direct relationship with green product innovation, but IT integration has an insignificant relationship with green product innovation. Second, the results show that three IT capabilities have positively influenced knowledge management. Third, the results confirm that KM has a significant positive effect on GPI. Finally, the outcomes confirmed that knowledge management positively and significantly mediates between all IT capabilities and GPI in the indirect relationship.

Elucidating molecular characterization of chlorpyrifos and profenofos degrading distinct bacterial strains for enhancing seed germination potential of Gossypium arboreum L.

Chlorpyrifos (CP) and profenofos (PF) are organophosphate pesticides (OPs) widely used in agriculture and are noxious to both fauna and flora. The presented work was designed to attenuate the toxicity of both pesticides in the growth parameters of a cotton crop by applying plant growth-promoting rhizobacteria (PGPR), namely Pseudomonas aeruginosa PM36 and Bacillus sp. PM37. The multifarious biological activities of both strains include plant growth-promoting traits, including phosphate solubilization; indole-3-acetic acid (IAA), siderophore, and HCN production; nitrogen fixation; and enzymatic activity such as cellulase, protease, amylase, and catalase. Furthermore, the molecular profiling of multi-stress-responsive genes, including acdS, ituC, czcD, nifH, and sfp, also confirmed the plant growth regulation and abiotic stress tolerance potential of PM36 and PM37. Both strains (PM36 and PM37) revealed 92% and 89% of CP degradation at 50 ppm and 87% and 81% at 150 ppm within 7 days. Simultaneously 94% and 98% PF degradation was observed at 50 ppm and 90% and 92% at 150 ppm within 7 days at 35 °C and pH 7. Biodegradation was analyzed using HPLC and FTIR. The strains exhibited first-order reaction kinetics, indicating their reliance on CP and PF as energy and carbon sources. The presence of opd, mpd, and opdA genes in both strains also supported the CP and PF degradation potential of both strains. Inoculation of strains under normal and OP stress conditions resulted in a significant increase in seed germination, plant biomass, and chlorophyll contents of the cotton seedling. Our findings indicate that the strains PM36 and PM37 have abilities as biodegraders and plant growth promoters, with potential applications in crop sciences and bioremediation studies. These strains could serve as an environmentally friendly, sustainable, and socially acceptable solution to manage OP-contaminated sites.

Identification and In Silico Analysis of a Homozygous Nonsense Variant in TGM1 Gene Segregating with Congenital Ichthyosis in a Consanguineous Family.

Background and Objectives: Lamellar ichthyosis is a rare skin disease characterized by large, dark brown plate-like scales on the entire body surface with minimum or no erythema. This phenotype is frequently associated with a mutation in the TGM1 gene, encoding the enzyme transglutaminase 1 which plays a catalytic role in the formation of the cornified cell envelop. The present study aimed to carry out clinical and genetic characterization of the autosomal recessive lamellar ichthyosis family from Balochistan. Materials and Methods: A consanguineous family with lamellar ichthyosis was enrolled from Balochistan, Pakistan. PCR amplification of all the exons and splice site junctions of the TGM1 gene followed by Sanger sequencing was performed on the genomic DNA. The identified variant was checked by In silico prediction tools to evaluate the effect of the variant on protein. Results: Sanger sequencing identified a homozygous nonsense variant c.131G >A (p.Trp44*) in the TGM1 gene that segregated in the autosomal recessive mode of inheritance in the family. The identified variant results in premature termination of transcribed mRNA and is predicted to cause a truncated or absent translation product transglutaminase-1 (TGase-1) accompanied by loss of catalytic activity, causing a severe clinical phenotype of lamellar ichthyosis in the patients. Conclusions: Here, we report a consanguineous lamellar ichthyosis family with a homozygous nonsense variant in the TGM1 gene. The variant is predicted as pathogenic by different In silico prediction tools.

Hospital Acquired Pathogenic Escherichia coli from Clinical and Hospital Water Samples of Quetta Balochistan.

A study was conducted to determine the prevalence and drug resistance of Escherichia coli present in urinary tract infected patients and hospital drinking water. A total of eighty urine samples from clinically suspected patients and thirty tap water samples from hospital vicinity were collected and analyzed for the presence of E. coli. The isolates were preliminary identified based on morphological characteristics, biochemical test and further confirmed by polymerase chain reaction (PCR) using uidA primer. Isolates were subjected to antibiogram studies and analyzed for the presence of drug resistance (ESBL blaCTX-M-15, tetA, and TMP-SMX dfrA1) and pathogenicity associated pyelonephritis-associated pili (PAP) and Heat-labile (LT) toxin genes. Urine samples 19/80 (23.75%) and water samples 8/30 (26.7%) were found contaminated with E. coli. It was found that 12/19 (63%) bacterial isolates were extended spectrum beta-lactamase (ESBL) producers in clinical and 6/8 (75%) in water isolates whereas tetracycline resistance in clinical and water isolates was 11/19 (58%) and 6/8 (75%), respectively. The trimethoprim resistance gene was confirmed in 12/19 (63%) in clinical and 2/8 (25%) in water isolates. All the clinical and water isolates were found carrying pili PAP gene. It was concluded that the presence of drug resistant and pathogenic E. coli in clinical and water samples is extremely alarming for public health due to cross contamination and bacterial transfer from clinical samples to water and vice versa.

Novel Curcumin-Encapsulated α-Tocopherol Nanoemulsion System and Its Potential Application for Wound Healing in Diabetic Animals.

Objective: This project was aimed at formulating a novel nanoemulsion system and evaluating it for open incision wound healing in diabetic animals. Methods: The nanoemulsions were characterized for droplet size and surface charge, drug content, antioxidant and antimicrobial profiling, and wound healing potential in diabetic animals. The skin samples excised were also analyzed for histology, mechanical strength, and vibrational and thermal analysis. Results: The optimized nanoemulsion (CR-NE-II) exhibited droplet size of26.76 ± 0.9 nm with negative surface charge (-10.86 ± 1.06 mV), was homogenously dispersed with drug content of68.05 ± 1.2%, released almost82.95 ± 2.2%of the drug within first 2 h of experiment with synergistic antioxidant (95 ± 2.1%) and synergistic antimicrobial activity against selected bacterial strains in comparison to blank nanoemulsion, and promoted significantly fast percent reepithelization (96.47%). The histological, vibrational, thermal, and strength analysis of selected skin samples depicted a uniform and even distribution of collagen fibers which translated into significant increase in strength of skin samples in comparison to the control group. Conclusions: The optimized nanoemulsion system significantly downregulated the oxidative stress, enhanced collagen deposition, and precluded bacterial contamination of wound, thus accelerating the skin tissue regeneration process.

Formulation and Evaluation of Chitosan-Gelatin Thermosensitive Hydrogels Containing 5FU-Alginate Nanoparticles for Skin Delivery.

(1) Background: Chitosan-gelatin-based thermosensitive hydrogel containing 5FU-alginate nanoparticles was formulated for the effective and sustained delivery of 5FU to the skin. (2) Methods: Alginate, a polysaccharide was used for the formulation of nanoparticles using a spray drying technique. Size, zeta potential, and surface morphology were investigated using a zetasizer and scanning electron microscope. The hydrogel was fabricated using chitosan and gelatin. Several important analyses were used to characterize these prepared topical hydrogels. The pH, visual transparency, rheological behavior, and swelling index of the prepared hydrogels were evaluated. The in vitro release studies were performed at different pH (5.5 and 7.4) and temperature (32 and 37 °C) conditions using a Franz diffusion cell. Ex vivo permeation and in vivo studies were performed using Sprague Dawley rats. (3) Results: Results show that spherical nanoparticles were produced at sizes of 202−254 nm and with zeta potentials of −43 to −38 mV. The prepared nanoparticles were successfully incorporated into chitosan-gelatin-based hydrogels using a glycerol 2-phosphate disodium salt hydrates crosslinker. Drug polymers and excipients compatibility and formulation of hydrogels was confirmed by ATR-FTIR results. The pH of the prepared hydrogels was in accordance with the skin pH. The viscosity of prepared hydrogel increased with temperature increase and phase transition (sol-gel transition) occurred at 34 °C. The release of drug was sustained in case of nanoparticles incorporated hydrogels (5FU-Alg-Np-HG) as compared to nanoparticles (5FU-Alg-Np) and simple hydrogels (5FU-HG) (ANOVA; p < 0.05). The premature and initial burst release of 5FU was prevented using 5FU-Alg-Np-HG. The release mechanism of 5FU from the 5FU-Alg-Np-HG diffusion was followed by swelling and erosion, as suggested by Korsmeyer-Peppas model. The prepared hydrogel proved to be non-irritant. Ex vivo permeation study across rat's skin suggests that permeability of nanoparticles (5FU-Alg-Np) was higher than the 5FU-Alg-Np-HG (ANOVA; p < 0.05). However, skin-related drug retention of 5FU-Alg-Np-HG was significantly higher than the 5FU solution, 5FU-Alg-Np, and 5FU-HG (ANOVA; p < 0.05). This was due to swelling of hydrogels in the lower layers of skin where the temperature is 37 °C. The higher concentration of 5FU in the skin is helpful for treatment of local skin cancer, such as melanoma, and actinic keratosis. In vivo results also confirmed maximum AUC, t1/2, and skin-related drug retention of 5FU-Alg-Np-HG. (4) Conclusions: Chitosan-gelatin-based hydrogels containing 5FU-Alg-Np possess exceptional properties, and can be used for the sustained delivery of 5FU for the treatment of local skin cancers.