Prebiotic-mediated gastroprotective potentials of three bacterial levans through NF-κB-modulation and upregulation of systemic IL-17A.

This study aimed to investigate whether the gastroprotective effects of three types of bacterial levans are correlated with their prebiotic-associated anti-inflammatory/antioxidant potentials. Three levans designated as LevAE, LevP, and LevZ were prepared from bacterial honey isolates; purified, and characterized using TLC, NMR, and FTIR. The anti-inflammatory properties of levan preparations were assessed in LPS-stimulated RAW 264.7 cell lines, while their safety and gastroprotective potentials were assessed in Wistar rats. The three levans significantly reduced ulcer number (22.29-70.05 %) and severity (31.76-80.54 %) in the ethanol-induced gastric ulcer model compared to the control (P < 0.0001/each), with the highest effect observed in LevAE and levZ (200 mg/each) (P < 0.0001). LevZ produced the highest levels of glutathione; catalase activity, and the lowest MDA levels (P = 0.0001/each). The highest anti-inflammatory activity was observed in LevAE and levZ in terms of higher inhibitory effect on IL-1ß and TNF-α production (P < 0.0001 each); COX2, PGE2, and NF-κB gene expression. The three levan preparations also proved safe with no signs of toxicity, with anti-lipidemic properties as well as promising prebiotic activity that directly correlated with their antiulcer effect. This novel study highlights the implication of prebiotic-mediated systemic immunomodulation exhibited by bacterial levans that directly correlated with their gastroprotective activity.

Carbohydrate microcapsules tailored and grafted for covalent immobilization of glucose isomerase for pharmaceutical and food industries.

Carrageenan is one of the most common carbohydrates utilised in the entrapment industry to immobilise cells and enzymes. However, it lacks functionality. Carrageenan has been grafted to produce fructose by covalently immobilising glucose isomerase (GI). Fructose is one of the most widely used sweeteners in beverages, food production, and the pharmaceutical business. Up to 91.1 U g-1 gel beads are immobilised by the grafted beads. Immobilized GI has a Vmax of 13.8 times that of the free enzyme. pH of immobilized GI was improved from 6.5-7 to 6-7.5 that means more stability in wide pH range. Also, optimum temperature was improved and become 65-75 °C while it was at 70 °C for free enzyme. The immovability and tolerance of the gel beads immobilised with GI over 15 consecutive cycles were demonstrated in a reusability test, with 88 percent of the enzyme's original activity retained, compared to 60 percent by other authors. These findings are encouraging for high-fructose corn syrup producers.

Lactobacillus-fermented yogurt exerts hypoglycemic, hypocholesterolemic, and anti-inflammatory activities in STZ-induced diabetic Wistar rats.

Hyperglycemia is a symptom of type 2 diabetes mellitus, a chronic metabolic disease characterized by elevated blood glucose concentrations. Antidiabetic drugs are common treatments for this metabolic disorder; however, they may have unpleasant side effects. This study hypothesized that probiotic fermented products could preserve nutritional value, maintain metabolic homeostasis, and attenuate the inflammatory response associated with diabetes while reducing side effects. Lactobacillus plantarum KU985438 and Lactobacillus rhamnosus KU985439 showed the lowest alfa-amylase enzyme (α-amylase) activity among 8 lactobacilli tested. These 2 strains were used to develop functional fermented milk products, and their antidiabetic efficacy was tested in induced diabetic Wistar rats. The treatment of diabetic rats with L. plantarum KU985438 or L. rhamnosus KU985439 fermented yogurt resulted in a considerable reduction in blood glucose concentrations (136.79% and 145.17%, respectively) and α-amylase concentrations (56.84% and 56.84%, respectively) compared with conventional treatments. Diabetes relief began after 4 days of yogurt consumption compared with drug-based treatment. Significant improvements in both liver and kidney enzyme concentrations were also observed, in addition to a significant increase in high-density lipoprotein cholesterol concentrations and improved lipid profiles. Inhibition in nuclear factor κB and an increase in Bcl-2 concentrations were also detected. Histopathological examination of both hepatic and pancreatic cells revealed the positive effects of the studied treatment compared with standard treatment. Therefore, the selected Lactobacilli, which has hypoglycemic potential, could be used to produce functional nutraceutical antidiabetic supplements.

Computational Investigation to Design Ofloxacin-Loaded Hybridized Nanocellulose/Lipid Nanogels for Accelerated Skin Repair.

The pharmaceutical application of biomaterials has attained a great success. Rapid wound healing is an important goal for many researchers. Hence, this work deals with the development of nanocellulose crystals/lipid nanogels loaded with ofloxacin (OFX) to promote skin repair while inhibiting bacterial infection. Ofloxacin-loaded hybridized nanocellulose/lipid nanogels (OFX-HNCNs) were prepared and evaluated adopting a computational method based on regression analysis. The optimized nanogels (OFX-HNCN7) showed a spherical outline with an encapsulation efficiency (EE), particle size (PS) and zeta potential (ZP) values of 97.53 ± 1.56%, 200.2 ± 6.74 nm and -26.4 ± 0.50 mV, respectively, with an extended drug release profile. DSC examination of OFX-HNCN7 proved the amorphization of the encapsulated drug into the prepared OFX-HNCNs. Microbiological studies showed the prolonged inhibition of bacterial growth by OFX-HNCN7 compared to the free drug. The cytocompatibility of OFX-HNCN7 was proved by Sulforhodamine B assay. Tissue repair was evaluated using the epidermal scratch assay based on cell migration in human skin fibroblast cell line, and the results depicted that cell treated with OFX-HNCN7 showed a faster and more efficient healing compared to the control. In overall, the obtained findings emphasize the benefits of using the eco-friendly bioactive nanocellulose, hybridized with lipid, to prepare a nanocarrier for skin repair.

Purification, amino acid sequence, and characterization of bacteriocin GA15, a novel class IIa bacteriocin secreted by Lactiplantibacillus plantarum GCNRC_GA15.

The bacteriocins produced by lactic acid bacteria (LAB) are attracting attention due to their promising applications in food and pharmaceuticals fields. Hence, a LAB strain, GCNRC_GA15, was isolated from Egyptian goat cheese, and molecularly identified as Lactiplantibacillus plantarum. This strain showed a wide antimicrobial spectrum, which was found to be of proteineous nature, suggesting that L. plantarum GCNRC_GA15 is a bacteriocin-producer. This bacteriocin (bacteriocin GA15) was partially purified using cation exchange, and hydrophobic interaction chromatography. Tricine SDS-PAGE analysis for the fraction showing bacteriocin activity has estimated the molecular mass to be 4369 Da. Furthermore, amino acid sequencing of this peptide has detected 34 amino acids, and comparing its amino acid sequence with those of some pediocin-like bacteriocins revealed that bacteriocin GA15 has the conserved sequence (YYGNGV/L) in its N-terminal region which identified bacteriocin GA15 as a pediocin-like bacteriocin. Bacteriocin GA15 showed good heat and pH stabilities, and its activity was enhanced after treatment with Tween 80 or Triton X-100. Bacteriocin production medium was statistically optimized using the Plackett-Burman and Central Composite designs. As a result, bacteriocin production increased from 800 to 12,800 AU/ml using the optimized medium in comparison with result recorded for the un-optimized medium.

Chitosan/ß-glycerophosphate in situ forming thermo-sensitive hydrogel for improved ocular delivery of moxifloxacin hydrochloride.

The aim of the current work is to develop a thermo-sensitive hydrogel system of moxifloxacin hydrochloride (MOX) for improved ocular delivery. Fifteen formulations were prepared at different concentrations of ß-glycerophosphate disodium salt (ß-GP) 12-20% (w/v) and chitosan (CS) 1.7-1.9% (w/v). The optimized MOX loaded thermo-sensitive hydrogel system (F8), consisting of CS (1.8%, w/v) and ß-GP (16%, w/v), showed optimum gelation temperature (35 °C) and gelation time (2 min), thus was selected for further investigations. It showed a significant decrease (p < 0.05) in the zeta potential value compared to CS solution with a favorable pH value (7.1) and confirmed thermoreversible behavior. MOX loaded F8 displayed a porous structure under scanning electron microscopy. Rheological investigation of MOX loaded F8 revealed the presence of a strong hydrogel network with high elasticity along with a small loss factor of 0.08 indicating a great ease of gel formation. The release of MOX from F8 was found to be governed by a combined mechanism of diffusion and relaxation. Biological assessment of two concentrations of MOX loaded F8 (0.25 and 0.5%) was conducted using healthy and infected male albino New Zealand rabbits, where an improved and prolonged antibacterial activity against Staphylococcus aureus compared to plain MOX (0.5%), marketed MOX eye drops (0.5%), was shown. Moreover, histopathological examination of ocular tissues confirmed the antibacterial efficacy of the optimized formulation eight days post topical therapy. Consequently, the developed CS/ß-GP thermo-sensitive hydrogel system (F8) reveals a promising potential for enhancing the ocular delivery of MOX for treatment of bacterial infections.

Assessment of exopolysaccharides, bacteriocins and in vitro and in vivo hypocholesterolemic potential of some Egyptian Lactobacillus spp.

Lactobacilli probiotics have been suggested to reduce cholesterol with low side effects to host. Bacteriocins and exopolysaccharides (EPSs) production are two meaningful examples of functional applications of lactobacilli in the food industry. Eight Lactobacillus strains were isolated from some Egyptian fermented food and tested for their probiotic properties. Analysis of the monosaccharide composition by thin layer chromatography showed the presence of glucose, galactose and unknown sugar. The main functional groups of EPSs were elucidated by Fourier-Transform Infrared Spectroscopy. Their fermentation cultures displayed powerful antioxidant activities extending from 97.5 to 99%, 40-75% for their EPSs and free cells, respectively, and exhibited in vitro cholesterol downgrading from 48 to 82% and 72 to 91% after 48 and 120 h, respectively. Their EPSs showed good anticancer activities against carcinoma cells with low IC50 values for HCT-116, PC-3 and HepG-2 cells. To the best of our knowledge, there have been no previous reports on the potential of Lactobacillus EPSs activity against PC-3. The selected strains, L. plantarum KU985433 and L. rhamnosus KU985436 produced two different bacteriocins as detected by gel permeation chromatography with good antimicrobial activities. In vivo study demonstrated that feeding Westar rats with fermented milk exhibited greater cholesterol, LDL and blood triglyceride reduction for both strains. Whereas, HDL was increased by about 43 and 38%, respectively, and the atherogenic indices decreased.

Promising bioadhesive ofloxacin-loaded polymeric nanoparticles for the treatment of ocular inflammation: formulation and in vivo evaluation.

Our work tackles the combined advantages of both nanotechnology and the bioadhesive gel properties which were utilized to design an ocular drug delivery system that is capable to treat ocular inflammation. Nanoparticles encapsulating an antibiotic drug, ofloxacin, were fabricated using emulsion solvent evaporation technique adopting 23 full factorial design to evaluate the effect of formulation parameters: that is to say, the molecular weight of the polymer (polycaprolactone), amount of Kolliphor P188, and presence of the charge inducer (chitosan hydrochloride) on the measured responses: drug entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI) and zeta potential (ZP). The results show that the optimized LPCL-NP2 formulation (composed of low molecular weight polycaprolactone, 500 mg of Kolliphor P188, 0.25% chitosan hydrochloride, and 50 mg ofloxacin)  displayed a sphere shape with EE%, PS, PDI, and ZP values of 89.73 ± 0.04%, 195.4 ± 13.17 nm, 0.323 ± 0.01, and 55.4 ± 0.66 mV, respectively. DSC study confirmed the amorphous nature of the drug. The optimized nanoparticle formulation was then further incorporated into the following two ocular formulations: gel (LPCL-NP2-G4) and in situ forming gel (LPCL-NP2-ISG4). The penetration of optimized ocular formulations was assessed by confocal laser scanning microscopy. The antimicrobial study was conducted  for the following three ocular formulations: LPCL-NP2 presented as eye drops, LPCL-NP2-G4, and LPCL-NP2-ISG4 as well as the market product using rabbits which were infected in their eyes with Escherichia coli. Results revealed that rabbits treated with LPCL-NP2-ISG4 demonstrated a remarkable antibacterial efficacy and evident low bacterial growth which was additionally assured by the histopathological examination of eye biopsies compared with the other investigated groups. Thus, a novel ofloxacin-loaded nanoparticle formulation based on polycaprolactone is presented in the form of mucoadhesive non-irritating in situ forming ocular gel possessing a superior antibacterial activity. Graphical abstract.

Thermo-alkali-stable lipase from a novel Aspergillus niger: statistical optimization, enzyme purification, immobilization and its application in biodiesel production.

The influences of nutritional components affecting lipase production from the new Aspergillus niger using wheat bran as substrate were studied by employing Plackett-Burman and central composite statistical designs. Out of the 11 medium components tested, sucrose, KH2PO4 and MgSO4 at final concentrations of 3.0, 1.0 and 0.5 g/L, respectively, were reported to contribute positively to enzyme production (20.09 ± 0.98 U/g ds). The enzyme was purified through ammonium sulfate precipitation followed by Sephadex G-100 gel filtration. Molecular mass of the purified lipase was 57 kDa as evident on SDS-PAGE. Different methods of immobilization were studied and the highest immobilization yield of 81.7 ± 2.18% was reported with agarose (2%) and the optimum temperature was raised from 45 to 50 °C. Immobilized lipase could retain 80% of its original activity at 60 °C after 1 hr of incubation, and was stable at pH values between neutral and alkaline pH. Lipase-catalyzed transesterification process of fungal oil resulted in a fatty acid methyl ester yield consisting of a high percentage of polyunsaturated fatty acids (83.6%), making it appropriate to be used as winter-grade biodiesel. The operational stability studies revealed that the immobilized lipase could keep 70% of its total activity after 5 cycles of the transesterification process.

A stepwise optimization strategy to formulate in situ gelling formulations comprising fluconazole-hydroxypropyl-beta-cyclodextrin complex loaded niosomal vesicles and Eudragit nanoparticles for enhanced antifungal activity and prolonged ocular delivery.

Fungal keratitis and endopthalmitis are serious eye diseases. Fluconazole (FL) is indicated for their treatment, but suffers from poor topical ocular availability. This study was intended to improve and prolong its ocular availability. FL niosomal vesicles were prepared using span 60. Also, polymeric nanoparticles were prepared using cationic Eudragit RS100 and Eudragit RL100. The investigated particles had adequate entrapment efficiency (EE%), nanoscale particle size and high zeta potential. Subsequently, formulations were optimized using full factorial design. FL-HP-ß-CD complex was encapsulated in selected Eudragit nanoprticles (FL-CD-ERS1) and niosmal vesicles. The niosomes were further coated with cationic and bioadhesive chitosan (FL-CD-Nios-ch). EE% for FL-CD-ERS1 and FL-CD-Nios-ch formulations were 76.4% and 61.7%; particle sizes were 151.1 and 392 nm; also, they exhibited satisfactory zeta potential +40.1 and +28.5 mV. In situ gels were prepared by poloxamer P407, HPMC and chitosan and evaluated for gelling capacity, rheological behavior and gelling temperature. To increase the precorneal residence time, free drug and selected nano-formulations were incorporated in the selected in situ gel. Release study revealed sustained release within 24 h. Permeation through excised rabbits corneas demonstrated enhanced drug flux and large AUC0-6h in comparison to plain drug. Corneal permeation of selected formulations labeled with Rhodamine B was visualized by Confocal laser microscopy. Histopathological study and in vivo tolerance test evidenced safety. In vivo susceptibility test using Candida albicans depicted enhanced growth inhibition and sustained effect. In this study the adopted stepwise optimization strategy combined cylodextrin complexation, drug nano-encapsulation and loading within thermosenstive in situ gel. Finally, the developed innovated formulations displayed boosted corneal permeation, enhanced antifungal activity and prolonged action.

Formulation and Evaluation of Novel Hybridized Nanovesicles for Enhancing Buccal Delivery of Ciclopirox Olamine.

Ciclopirox olamine (CPO) is a topical wide-spectrum antimycotic agent that possesses antifungal, antibacterial and anti-inflammatory activities. Loading CPO into a hybridized vesicular system is expected to enhance its buccal permeation and hence, therapeutic activity, whereas the frequent administration and side effects are reduced. Vesicular systems with high penetration ability were prepared based on cholesterol, Lipoid S45 or Phospholipon 90H, with span 60 while incorporating a penetration enhancer (Labrafac or labrasol) followed by full assessment of their size, entrapment efficiency, and drug release profiles. The optimum formulation, composed of Lipoid S45 and Labrafac, possessed the smallest vesicle size (346.1 nm), highest entrapment efficiency (94.4%), and sustained CPO release pattern, and was characterized for its morphology and thermal properties. This powerful mixture of the penetration enhancers (Lipoid S45 and Labrafac) in the designed hybridized vesicles was thoroughly investigated for their characteristics after being incorporated in bioadhesive gel. Moreover, enhanced antifungal activity was demonstrated either upon testing the designed formulation on agar plates or in vivo upon treating infected rabbits with the proposed formulation. Results suggest that the presented bioadhesive gel incorporating the CPO-loaded vesicles can be a promising delivery system that can offer a prolonged localized antifungal treatment with enhanced therapeutic effect.

Complete genome sequence and comparative analysis of two potential probiotics Bacillus subtilis isolated from honey and honeybee microbiomes.

BACKGROUND: We have previously isolated Bacillus subtilis HMNig-2 and MENO2 strains, from honey and the honeybee gut microbiome respectively, and demonstrated these strains to produce levansucrase with potential probiotics characteristics. Here we report their complete genome sequence and comparative analysis with other and other B. subtilis strains. RESULTS: The complete genome sequences of Bacillus subtilis HMNig-2 and MENO2 were de novo assembled from MiSeq paired-end sequence reads and annotated using the RAST tool. Whole-genome alignments were performed to identify functional differences associated with their potential use as probiotics. CONCLUSIONS: The comparative analysis and the availability of the genome sequence of these two strains will provide comprehensive analysis about the diversity of these valuable Bacillus strains and the possible impact of the environment on bacterial evolution. SIGNIFICANCE AND IMPACT OF STUDY: We introduce complete genome sequence of two new B. subtilis strains HMNig-2 and MENO2 with probiotic potential and as cell factories for the production of levan and other valuable components for pharmaceutical and industrial applications.

Synthesis and Evaluation of New Coumarin Derivatives as Antioxidant, Antimicrobial, and Anti-Inflammatory Agents.

New pyranocoumarin and coumarin-sulfonamide derivatives were prepared and evaluated for their antioxidant, antimicrobial, and/or anti-inflammatory activities. Coumarin-sulfonamide compounds 8a-d demonstrated significant antioxidant activity, while 7c,d, 8c,d, and 9c,d exhibited antimicrobial activity equal to or higher than the standard antimicrobials against at least one tested microorganism. Regarding the anti-inflammatory testing, pyranocoumarins 2b, 3a,b and 5c and coumarin-sulfonamide compound 9a showed more potent antiproteinase activity than aspirin in vitro; however, five compounds were as potent as aspirin. The anti-inflammatory activity of the promising compounds was further assessed pharmacologically on formaldehyde-induced rat paw oedema and showed significant inhibition of oedema. For in vitro COX-inhibitory activity of coumarin derivatives, pyranocoumarin derivative 5a was the most selective (SI = 152) and coumarin-sulfonamide derivative 8d was most active toward COX-2 isozyme. The most active derivatives met the in silico criteria for orally active drugs; thus, they may serve as promising candidates to develop more potent and highly efficient antioxidant, antimicrobial, and/or anti-inflammatory agents.

Functionalized κ-carrageenan/hyperbranched poly(amidoamine)for protease immobilization: Thermodynamics and stability studies.

Hyperbranched polyamidoamine (PAMAM) has a high density of surface amino groups. This feature was exploited in the surface modification of κ-carrageenan gel beads for successful protease immobilization. The optimum PAMAM pH was at 2.1 and 9.3. However, treatment of κ-carrageenan gel beads at the higher pH showed re-usability for more than seven successive times. As a result of central composite design optimization, the maximum immobilization yield was obtained by soaking 8 U for 24 h. The comparative thermodynamics studies showed an enhancement in the thermal stability at high temperature for the immobilized protease as well as increased half-life time from 24.06 min to 79.95 min. Also, the D-values increased from 165.03 min to 548.23 min for free and immobilized enzyme, respectively. Moreover, the enzyme stability enhancement for the immobilized protease catalyst was accompanied with a remarkable increase in the enthalpy and in the free energy. Immobilized protease onto Carr-PAMAM gel beads can retain 89% of its initial activity and lost only 11% after 8 weeks of storage at 4 °C. Furthermore, an effective removal of silver from used X-ray film by the immobilized protease was achieved for six repeated cycles.

Metabolic profiling of a polyphenolic-rich fraction of Coccinia grandis leaves using LC-ESI-MS/MS and in vivo validation of its antimicrobial and wound healing activities.

A polyphenolic-rich fraction (CG50) was obtained from the methanol extract of Coccinia grandis leaves by chromatographic fractionation over a Diaion column using 50% aqueous methanol. LC-ESI-MS/MS analysis of CG50 showed the presence of six flavonoids, namely quercetin-hexoside deoxyhexoside (rutin), quercetin-hexoside deoxyhexoside (quercetin-3-O-neohesperidoside), kaempferol-hexoside deoxyhexoside (kaempferol-3-O-rutinoside), kaempferol-hexoside deoxyhexoside (kaempferol-3-O-neohesperidoside), kaempferol-3-O-glucoside, and kaempferol-hexoside in addition to the presence of two secoiridoids which are oleuropein and ligstroside. CG50 hydrogel showed a pronounced inhibition of the bacterial growth in wounds infected by Bacillus cereus in rats comparable to those treated with hydrogel base only showing 85.08 and 16.50% inhibition for the bacterial growth for the CG50 hydrogel and hydrogel base, respectively. The antimicrobial activity of CG50 hydrogel was close to that of fucidin during all days of treatment. Rats treated with CG50 hydrogel showed remarkable healing ability of the wound compared to other groups and approaching that of fucidin. This was clearly manifested by the clear formation of scars with obvious reduction in the wound size together with the appearance and re-growth of hair. This was further confirmed by the histopathological study of skin tissues as well as by the evaluation of the percentages of collagen fiber deposition. CG50 hydrogel showed 18.71% collagen fiber deposition comparable to the untreated group that showed 6.84% collagen fiber deposition and approaches that of the fucidin group. It was concluded that Coccinia grandis could be used as a natural wound healing agent that further consolidated its traditional use as a wound dressing.

Immobilization of xylanase on modified grafted alginate polyethyleneimine bead based on impact of sodium cation effect.

Alginate- polyethyleneimine gel beads modified by using 0.3 M Na+ were used for covalent immobilization of Aspergillus flavus xylanase. SEM images showed distorted structure with addition of Na+ that impaired the egg-box structure formation offered much covalent binding with xylanase. Immobilization onto (Alg+PEI/Na+) showed an enhancement in the operational stability, immobilization efficiency as well as immobilization yield. Covalent immobilization of xylanase onto (Alg+PEI/Na+) enhanced xylanase activity over a wide range of pHs (4-5.5) comparable to its free formula. As well as an increase in reaction temperature up to 60°C. However, immobilized formula of enzyme showed abroad thermal stability that it retained 79.0% of its initial activity at 70°C up to 30 min whereas, free formula completely lost its activity at this temperature. Thermodynamics studies showed an enhancement in thermal stability at high temperature for the immobilized xylanase. i.e. At 70°C the t1/2 and D-value for free formula of enzyme increased from 24 to165 min and from 79.95to 548.23 min, respectively. Moreover, the enzyme stability enhancement for immobilized formula of xylanase was proved with a remarkable increase in enthalpy and free energy. 93% of the immobilized xylanase activity was retained over 6 weeks of storage at -4°C.

Development of Promising Thiopyrimidine-Based Anti-cancer and Antimicrobial Agents: Synthesis and QSAR Analysis.

Objective & Methodology: New hybrids of thiopyrimidine-five/six heterocyclic rings were synthesized and in vitro evaluated for their antiproliferative activity against three human cancer cell lines, namely HCT116 (human colorectal carcinoma), PC-3 (human prostate adenocarcinoma) and HepG2 (human liver carcinoma) cell lines. The most potency was elicited by the target candidates against the viability of HCT116 cell lines. It was higher than that obtained by the positive control 5-Fluorouracil (IC50 range; 0.11-0.49 µM, IC50, 5-FU; 1.10 µM). Results: Cell cycle analysis and apoptosis activation revealed that compound 20 induced G2/M phase arrest and apoptosis in HCT116 cells. In addition, compound 20 activates the caspases-9 and -3, a process which might mediate the apoptosis of HCT116 cells. Quantitative structure activity relationship study was done and revealed a high predictive power R2 suggesting goodness of the models. Conclusion: Furthermore, there is a good agreement between the observed pIC50 and the predicted pIC50 values, in addition, the low RMSD and standard error values indicate the accuracy of the model. Antimicrobial evaluation revealed that some of these compounds exhibited significant activities against the tested pathogenic bacteria and fungi, wherein compounds 7a, 14, 15a, 21a, produced the most potent and broad spectrum antibacterial and antifungal potency that was equivalent to that revealed by Vibramycin and Ketoconazole (MIC; 125 µg/mL). Moreover, compounds 15a, 21c, investigated dual potent antimicrobial and anticancer activity.

A potential antibacterial wound dressing of cefadroxil chitosan nanoparticles in situ gel: Fabrication, in vitro optimization and in vivo evaluation.

Wound healing following skin injury is a natural phenomenon that usually lacks quality, rapidity, and aesthetics. Thus, the purpose of this study was to fabricate a new easily applied in situ gel of cefadroxil (CDX) loaded chitosan nanoparticles (CDX-CSNPs) that could promote wound healing, capable of inhibiting the possible accompanying bacterial infection. The nanoparticles were prepared by double emulsion technique and the influence of formulation parameters on drug entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI) and zeta potential (ZP) were investigated using a full factorial design. The results show that the optimized CDX-CSNP1 composed of low molecular weight chitosan (0.2%w/v) was spherical with EE%, PS, PDI and ZP of 84.25 ±â€¯0.02, 408.30 ±â€¯53.17 nm, 0.458 ±â€¯0.048 and 22.80 ±â€¯0.57 mV, respectively. DSC and XRD studies confirmed the amorphous nature of the drug. After ensuring the safety and non toxicity of CDX-CSNP1 in situ gel through cytotoxic study, the antibacterial activity was evaluated using a rat skin infection model against Staphylococcus aureus. Compared to the rats treated with free CDX, the CDX-CSNP1 treated group revealed a remarkable accelerated wound healing process and bacterial clearance which was further confirmed by the histopathological examination of skin biopsies.

Optimization of pectinase immobilization on grafted alginate-agar gel beads by 24 full factorial CCD and thermodynamic profiling for evaluating of operational covalent immobilization.

Pectinase produced by a honey derived from the fungus Aspergillus awamori KX943614 was covalently immobilized onto gel beads made of alginate and agar. Polyethyleneimine, glutaraldehyde, loading time and enzyme's units were optimized by 24 full factorial central composite design (CCD). The immobilization process increased the optimal working pH for the free pectinase from 5 to a broader range of pH4.5-5.5 and the optimum operational temperature from 55°C to a higher temperature, of 60°C, which is favored to reduce the enzyme's microbial contamination. The thermodynamics studies showed a thermal stability enhancement against high temperature for the immobilized formula. Moreover, an increase in half-lives and D-values was achieved. The thermodynamic studies proved that immobilization of pectinase made a remarkable increase in enthalpy and free energy because of enzyme stability enhancement. The reusability test revealed that 60% of pectinase's original activity was retained after 8 successive cycles. This gel formula may be convenient for immobilization of other industrial enzymes.

Improved vaginal retention and enhanced antifungal activity of miconazole microsponges gel: Formulation development and in vivo therapeutic efficacy in rats.

Traditional azole antifungal formulations suffer from poor retention in the vaginal cavity, irritation and burning of the vaginal area. In the present work, we aim at the development of a novel miconazole (MCZ) microsponges gel as an attractive dosage form for vaginal candidiasis. The proposed formula has the potential to minimize the local side effects of the drug due to the controlled release characteristic, which increases patient compliance. Moreover, the mucosal retention effect of the microsponges in addition to the bioadhesion property of Carbopol gel prolongs the retention of the dosage form in the vagina and consequently improves the therapeutic efficiency. MCZ microsponges were prepared applying Quasi emulsion method using Eudragit RS100. The effect of formulation factors, namely, drug:polymer ratio (1:1, 2:1 and 4:1), the amount of poly vinyl alcohol (PVA) (25, 50 and 75mg) and the volume of organic solvent (2.5, 5, 10mL) on the characteristics of MCZ microsponges has been investigated. The microsponges were optimized regarding the production yield (68.8±6.4%), particle size (78.2±2.1µm), entrapment efficiency (92.9±1.9%) and release rate (Q150 51.8±2.5%). The selected formula was further evaluated for its, flowability, porosity and surface morphology. MCZ microsponges were incorporated into Carbopol gel, then the viscosity and bioadhesion were examined. The in vitro antifungal activity of MCZ microsponges gel was comparable to the market product. In vivo, MCZ microsponges vaginal gel was more effective than the market product (p<0.05) in eradicating Candida infection in rats, which was supported by the histopathological findings.