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Biofilm-mediated osteomyelitis presents significant therapeutic challenges. Given the limitations of existing osteomyelitis treatment approaches, there is a distinct need to develop a localized drug delivery system that is biocompatible, biodegradable, and capable of controlled antibiotic release. Multivesicular liposomes (MVLs), characterized by their non-concentric vesicular structure, distinct composition, and enhanced stability, serve as the system for a robust sustained-release drug delivery platform. In this study, various hydrogel formulations composed of poloxamer 407 and other hydrogels, incorporating vancomycin hydrochloride (VAN HL)-loaded MVLs (VAN HL-MVLs), were prepared and evaluated. The optimized VAN HL-MVL sol-gel system, consisting of poloxamer 407 and hyaluronic acid, successfully maintained drug release for up to 3 weeks and exhibited shear-thinning behavior at 37°C. While complete drug release from MVLs alone took place in 312 h, the hydrogel formulation extended this release to 504 h. The released drug effectively inhibited the Staphylococcus aureus biofilms growth within 24 h and methicillin-resistant S. aureus biofilms within 72 h. It also eradicated preformed biofilms of S. aureus and methicillin-resistant S. aureus in 96 and 120 h, respectively. This injectable in situ gel system incorporating VAN HL-MVLs holds potential as an alternative to undergoing multiple surgeries for osteomyelitis treatment and warrants further studies. [ABSTRACT FROM AUTHOR]

Source coding has a rich and long history. However, a recent explosion of multimedia Internet applications (such as teleconferencing and video streaming, for instance) renews interest in fast compression that also squeezes out as much redundancy as possible. In 2009 Jarek Duda invented his asymmetric numeral system (ANS). Apart from having a beautiful mathematical structure, it is very efficient and offers compression with a very low coding redundancy. ANS works well for any symbol source statistics, and it has become a preferred compression algorithm in the IT industry. However, designing an ANS instance requires a random selection of its symbol spread function. Consequently, each ANS instance offers compression with a slightly different compression ratio. The paper investigates the compression optimality of ANS. It shows that ANS is optimal for any symbol sources whose probability distribution is described by natural powers of 1/2. We use Markov chains to calculate ANS state probabilities. This allows us to precisely determine the ANS compression rate. We present two algorithms for finding ANS instances with a high compression ratio. The first explores state probability approximations in order to choose ANS instances with better compression ratios. The second algorithm is a probabilistic one. It finds ANS instances whose compression ratios can be made as close to the best ratio as required. This is done at the expense of the number θ of internal random "coin" tosses. The algorithm complexity is O (θ L 3) , where L is the number of ANS states. The complexity can be reduced to O (θ L log 2 L) if we use a fast matrix inversion. If the algorithm is implemented on a quantum computer, its complexity becomes O (θ (log 2 L) 3) . [ABSTRACT FROM AUTHOR]

Current study intended to prepare and evaluate phospholipid-based, mixed micelles (MMs) to improve the ocular delivery of posaconazole (POS), a broad-spectrum antifungal drug. For this, MMs based on egg phosphatidylcholine (EPC), as the main component, in combination with various bile salts (sodium cholate (NaC), sodium deoxycholate (NaDC), sodium taurocholate (NaTC)) or non-ionic surfactants (Pluronic® F-127, Pluronic® F-68, Tween 80, Labrasol® ALF, and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)) were prepared. Particle size, polydispersity index, zeta potential and entrapment efficiency were evaluated to optimize the composition and preparation method of the MMs. Finally, morphology, stability, in vitro release pattern, and in vitro antifungal activity of the optimized formulation were investigated. Among the prepared MMs, vesicles composed of EPC: TPGS with a molar ratio of 70:30, prepared by the thin-film hydration method, showed more appropriate features. Among the prepared MMs, vesicles composed of EPC: TPGS with a molar ratio of 70:30 showed more appropriate features, including an entrapment efficiency (EE) greater than 80%, spherical shape morphology, an average particle size of about 58 nm, desirable stability over a month, slow-release without a noticeable initial burst, and a significantly higher in vitro antifungal activity in comparison with the drug suspension. Therefore, this formulation was selected as the optimal MMs and could be considered as a promising carrier for topical ocular delivery of POS. Graphical Abstract [ABSTRACT FROM AUTHOR]

Microemulsion-based gels (MBGs) were prepared for transdermal delivery of lidocaine and evaluated for their potential for local anesthesia. Lidocaine solubility was measured in various oils, andphase diagrams were constructed tomapthe concentration range of oil, surfactant, cosurfactant, and water for oil-in-water (o/w) microemulsion (ME) domains, employing the water titrationmethod at different surfactant/cosurfactant weight ratios. Refractive index, electrical conductivity, droplet size, zeta potential, pH, viscosity, and stability of fluid o/w MEs were evaluated. Carbomer® 940 was incorporated into the fluid drug-loaded MEs as a gelling agent. Microemulsion-based gels were characterized for spreadability, pH, viscosity, and in-vitro drug release measurements, and based on the results obtained, the best MBGs were selected and subsequently subjected to ex-vivo rat skin permeation anesthetic effect and irritation studies. Data indicated the formation of nano-sized droplets of MEs ranging from 20 - 52 nm with a polydispersity of less than 0.5. In-vitro release and ex-vivo permeation studies on MBGs showed significantly higher drug release and permeation in comparison to the marketed topical gel. Developed MBG formulations demonstrated greater potential for transdermal delivery of lidocaine and advantage over the commercially available gel product, and therefore, they may be considered as potential vehicles for the topical delivery of lidocaine. [ABSTRACT FROM AUTHOR]

Aim: To develop quercetin-loaded poly(caprolactone) (PCL)/soybean phosphatidylcholine (PC) films coated with silver (Ag) to prevent the formation of postoperative adhesions (POA). Materials & methods: Films were prepared using the solvent casting method, coated with Ag, and underwent in vitro tests. In vivo studies were conducted employing an animal model of sidewall defect and cecum abrasion. Results: Films showed sustained release behavior of quercetin and Ag. Coating films with Ag improved their antimicrobial activity. In vivo studies confirmed superior antiadhesion properties of films compared with the control groups evaluated by gross observation, histochemical staining and immunohistochemistry analyses. Conclusion: Ag-Q-PCL-PC films are a potential candidate to prevent POA by acting as a sustained release delivery system and physical barrier. [ABSTRACT FROM AUTHOR]

Mobilization and engraftment of Hematopoietic Stem Cells (HSCs) are challenging issues in Autologous HSC transplantation (AHSCT) so several attempts such as colony-stimulating factors (CSF) and plerixafor have been used for enhancement of HSCs mobilization and engraftment. In this randomized, double-blind and placebo-controlled study, we evaluated the melatonin's efficacy and safety, as endogenous CSF inducer, co-administered with Filgrastim in mobilizing and engraftment of HSC. AHSCT patients were randomized to receive either Melatonin or placebo plus filgrastim. Of Fifty-one patients, 26 patients received the melatonin (In mobilization phase 3 mg sublingual twice daily, then 9 mg single dose 30 min before apheresis session and then 3 mg twice daily from +1 until engraftment) and 25 patients received the placebo. The mean number of CD34 cells/kg × 106 in the melatonin group was 6.54 versus 4.22 in the placebo group (p = 0.025). The mean day to neutrophil engraftment in the melatonin group was 11.69 ± 2.093, whereas 12.68 ± 2.42 days in the placebo group (p = 0.021). In this study, the second apheresis session requirement, the use of plerixafor and hospital stay duration, were comparable between the two groups. Considering the result of the study, it could be suggested that melatonin plus Filgrastim can be effectively used in AHSCT patients to enhance the number of peripheral CD34 cells/kg × 106 and decrease the day number of neutrophil engraftment. [ABSTRACT FROM AUTHOR]

Illegal and excessive use of veterinary antibiotics as a food additive for growth promotion in livestock can lead to allergic reactions and antibiotic resistance, which is a worldwide concern. A biochip-based semi-quantitative screening method of antimicrobial residues in milk was validated based on Commission Decision 2002/657/EC and the European guideline to validate screening methods for veterinary medicines. This multi-analytical screening method enables to determine of 3 beta-lactams (cefalexin, ampicillin, and cefuroxime) simultaneously. Analysis of 20 blank and 20 spiked milk samples showed that for all 3 antibiotic residues, the positivity threshold T was above cut-off value Fm, and no false-positive results were obtained for all 3 antibiotics. All detection capabilities (CCβ) were below Maximum Residue Level (MRL) authorized by European Commission. 47 UHT cow's milk samples collected from Tehran province, IR Iran, were screened, and compliance was found in 100% of samples. This study found that the biochip method is valid to determine antibiotic residues in milk samples at the measured validation levels. The method was fast, simple, and able to simultaneous screen three families of beta-lactams from a single milk sample with almost no sample preparation. [ABSTRACT FROM AUTHOR]

Coronavirus disease-19 (COVID-19) pandemic, caused by SARS-CoV-2, has gradually spread worldwide, becoming a major public health event. This situation requires designing a novel antiviral agent against the SARS-CoV-2; however, this is time-consuming and the use of repurposed medicines may be promising. One such medicine is favipiravir, primarily introduced as an anti-influenza agent in east world. The aim of this study was to evaluate the efficacy and safety of favipiravir in comparison with lopinavir-ritonavir in SARS-CoV-2 infection. In this randomized clinical trial, 62 patients were recruited. These patients had bilateral pulmonary infiltration with peripheral oxygen saturation lower than 93%. The median time from symptoms onset to intervention initiation was seven days. Favipiravir was not available in the Iranian pharmaceutical market, and it was decided to formulate it at the research laboratory of School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. The patients received favipiravir tablet at a dose of 1600 mg orally twice a day for day one and then 600 mg orally twice a day for days 2 to 6. In the second group, the patients received lopinavir-ritonavir combination tablet at a dose of 200/50 mg twice a day for seven days. Fever, cough, and dyspnea were improved significantly in favipiravir group in comparison with lopinavir-ritonavir group on days four and five. Mortality rate and ICU stay in both groups were similar, and there was no significant difference in this regard (P = 0.463 and P = 0.286, respectively). Chest X-ray improvement also was not significantly different between the two groups. Adverse drug reactions occurred in both groups, and impaired liver enzymes were the most frequent adverse effect. In conclusion, early administration of oral favipiravir may reduce the duration of clinical signs and symptoms in patients with COVID-19 and hospitalization period. The mortality rate also should be investigated in future clinical trials. [ABSTRACT FROM AUTHOR]

Since 1980 after introducing the concept of live cell encapsulation by Lim et al., this technology has received enormous attention. Several studies have been conducted to improve this technique; different polymers, either natural or synthetic, have been used as microcapsules' making materials and different substances as coating layers. Literature review leads us to the conclusion that alginate (Alg) multilayer microcapsules and, in particular, alginate-poly l-lysine (PLL)-alginate (APA) are the most used structures for live cell encapsulation. Although, disadvantages of PLL (e.g., weak mechanical strength and low biocompatibility) made researchers work on other cationic polymers to find an alternative. This review aims to discuss more popularly suggested cationic polymers such as poly l-ornithine (PLO), chitosan, etc. As alternatives for PLL and, more importantly, we want to take a closer look to see which one of these systems are closer to clinical applications. [ABSTRACT FROM AUTHOR]

Human exposure to polycyclic aromatic hydrocarbons (PAHs) is known as a carcinogen risk factor. In this study, a gas chromatography-mass spectrometry (GC-MS) technique combined with the QuEChERS extraction method was developed for concurrent analysis of 10 polycyclic aromatic hydrocarbons (PAHs) in Iranian traditional Sangak bread samples. The method was validated by determining different parameters, including; linearity, accuracy, precision, limit of detection (LOD) and limit of quantitation (LOQ). Calibration curves showed a linear relationship in the concentration range of 10-500 ng/g with a coefficient of determination (R2) ranged between 0.994 and 0.999. The obtained mean recoveries were 92-106% with the relative standard deviations (RSDs) in the range of 3-7% with an acceptable precision (RSD < 20%). The Limit of detections (LODs) for different PAHs were between 0.14-0.78 ng/g, while the limit of quantitation (LOQ) was 0.46-2.60 ng/g. Matrix effect studies showed that the analytes concluded signal suppressions or enhancements. Therefore, spiked calibration curves were used for overcoming this issue. The result of Sangak bread samples analysis using the validated method showed that 9 (19.4%) out of 47 Sangak bread samples were contaminated with phenanthrene (PHE) and anthracene (ANT) at the mean level of 10.08 ± 6.38 ng/g which were higher than the permissible limit of European Commission regulatory control value for BaP (1 µg/kg of wet weight) in processed cereal-based foods and baby foods for infants and young children. [ABSTRACT FROM AUTHOR]

Staphylococcal Enterotoxin B (SEB) is a bacterial antigen that is responsible for food poisoning in humans. Cholera toxin is the most important virulence factor in Vibrio cholera. The gene sequence of ctxB and seb were obtained from GenBank and Site-specific mutagenesis (L45R, Y89A, and Y94A, respectively) was performed in the seb gene sequence, Three-dimensional protein structure, modeling, secondary and tertiary structure, immunogenicity, and allergenic sites were predicted using online bioinformatics software. In addition to gene codons to increase the expression of the rSEB-CTXB protein in the E.coli BL21 DE3 host, different parameters affecting expression were also optimized. The thermodynamic analysis of mRNA structure was performed to investigate the stability at the transcriptional stage. The physicochemical parameters and the predicted protein structure and quality of the structures were predicted. Linear and conformational epitopes were also considered. The antigen tendencies and estimated sensitivity were performed using Algpred software. The chimeric protein is topologically close to native proteins and all domains had surface accessibility and showed the highest antigenicity index. The Codon Adaptation Index of chimer increased from 0.7 to 0.89. The protein structure showed that the predicted structure had good quality. The evaluation of silicon chimeric proteins showed that the model is suitable for the stability and solubility of mRNA. Constitutive and linear epitopes were observed in all three chimeric protein domains. This study showed that these results could have implications for the production of chimeric immunogen antigen against the toxicity of Staphylococcus aureus and Vibrio cholerae in animal models. The ctxB and Seb genes were examined for rare codons, and the genes were optimized, followed by bioinformatics. Protein expression was assessed by PAGE-SDS and Western blotting. The expression of recombinant protein from the synthetic gene led to the production of a protein with a size 51 kD. Conclusion: According to the results of bioinformatics studies and recombinant protein expression, it can be used as an immunogen for safety studies against Vibrio cholerae producing Cholera toxin and Staphylococcus aureus producing enterotoxin SEB. [ABSTRACT FROM AUTHOR]

To evaluate the effect of ciprofloxacin concentration and cement geometry on release, mechanical, and antibacterial properties of PMMA bone cement. Significance: Cements are used in different geometries and drug concentrations. These can affect cement strength, drug release behavior, and its antibacterial activity. Antibiotic-loaded bone cement (ALBC) containing 2.5, 5.0, and 10.0 wt% ciprofloxacin were prepared as slab, rectangular prism and short cylinder. Drug release and compression strength of the cements were investigated for 28 days at 37 °C. The ALBC efficacies against prevalent bone infection bacteria, S. aureus, E. coli, and P. aeruginosa, were investigated. Drug determination was by HPLC. A two-stage behavior of fast release through dissolution/diffusion (stage A; <96 h) and 2–5 times slower Fickian diffusion (stage B; 96–672 h) was observed. Significant differences for release rate were observed among different geometries in the order of cylinder > prism > slab, in correlation with systems' thickness, indicating lower drug depletion in thicker systems. Release rates were proportional to concentration for 2.5 and 5% systems. At 10.0% loading, however, apparently interconnected channels and higher porosity reduced the diffusional resistance and provided higher release rates than what expected from concentration increment. Growth of Gram-negative bacteria and S. aureus was inhibited at the lowest dose of drug over 1 and 48 h, respectively. ALBCs with 5.0 and 10.0% ciprofloxacin showed decrease of compression strength to below ISO standard. Different properties of acrylic cements are affected by geometry and drug concentration and should be considered for optimized drug therapy. [ABSTRACT FROM AUTHOR]

Objectives. This study aimed to evaluate the efficacy of a combination of 1% nanocurcumin gel with 0.1% triamcinolone acetonide mouth rinse for oral lichen planus (OLP). Materials and Methods. This double-blind randomized clinical trial was conducted on 31 patients with erosive or ulcerative OLP. All patients received 0.1% triamcinolone mouth rinse and were then randomly divided into two groups for combination therapy with (I) %1 nanocurcumin gel or (II) placebo gel. The reticular-erosive-ulcerative (REU) score was calculated at baseline and at two and four weeks after the intervention. The changes in the mean REU score and the efficacy index were calculated to determine the level of improvement after two and four weeks. Data were analyzed using independent t-test, repeated measures ANCOVA, Mann–Whitney test, and chi-square test. P < 0.05 was considered statistically significant. Results. There were 14 patients in the nanocurcumin and 17 patients in the placebo group. A significantly higher decrease in the mean REU score was observed in the nanocurcumin compared with the placebo group (P < 0.001). The efficacy index was significantly higher in the nanocurcumin group (P < 0.001). Conclusion. Application of 1% nanocurcumin in combination with 0.1% triamcinolone acetonide can serve as an effective treatment strategy to enhance the level of improvement of lesions compared with the use of triamcinolone acetonide alone. [ABSTRACT FROM AUTHOR]

Purpose: Poly l-lysine (PLL) has been introduced as a strengthening covering layer for alginate microcapsules which are the most convenient way for cell encapsulation. Some disadvantages of PLL such as high price and low biocompatibility have prompted scientists to find better alternatives. Linear poly ethylene imine (LPEI), thanks to its highly similar structure to PLL, could be considered as a proper cost-effective alternative. In this study LPEI and PLL were compared as covering layers of cell-loaded alginate-LPEI-alginate (cALA) and alginate-PLL-alginate (cAPA) microcapsules. Methods: In addition to the physico-mechanical properties, the encapsulation efficiency, cell survival post encapsulation, cell viability, and cellular metabolic activity within the microcapsules were evaluated using trypan blue, live/dead cell staining, and MTT test, respectively. Results: Physico-mechanical evaluation of the microcapsules revealed that the cell microencapsulation process did not affect their shape, size, and mechanical stability. Although the encapsulation efficiency for cALA and cAPA was not different (P > 0.05), cell survival post encapsulation was higher in cALA than in cAPA (P < 0.05) which could be the reason for the higher cell viability and also cellular metabolic activity within these microcapsules in comparison to cAPA. Conclusion: Here, based on these results, ALA could be introduced as a preferable alternative to APA for cell encapsulation. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the novel application of a handheld near infra-red spectrophotometer coupled with classification methodologies as a screening approach in detection of adulterated lime juices. For this purpose, a miniaturized near infra-red spectrophotometer (Tellspec®) in the spectral range of 900-1700 nm was used. Three diffuse reflectance spectra of 31 pure lime juices were collected from Jahrom, Iran and 25 adulterated juices were acquired. Principal component analysis was almost able to generate two clusters. Partial least square discriminant analysis and k-nearest neighbors algorithms with different spectral preprocessing techniques were applied as predictive models. In the partial least squares discriminant analysis, the most accurate prediction was obtained with SNV transforming. The generated model was able to classify juices with an accuracy of 88% and the Matthew's correlation coefficient value of 0.75 in the external validation set. In the k-NN model, the highest accuracy and Matthew's correlation coefficient in the test set (88% and 0.76, respectively) was obtained with multiplicative signal correction followed by 2nd-order derivative and 5th nearest neighbor. The results of this preliminary study provided promising evidence of the potential of the handheld near infra-red spectrometer and machine learning methods for rapid detection of lime juice adulteration. Since a limited number of the samples were used in the current study, more lime juice samples from a wider range of variability need to be analyzed in order to increase the robustness of the generated models and to confirm the promising results achieved in this study. [ABSTRACT FROM AUTHOR]

In past decades, alginate-based multilayer microcapsules have been given important attention in various pharmaceutical investigations. Alginate-poly l lysine-alginate (APA) is studied the most. Due to the similarity between the structure of polyethyleneimine (PEI) and poly-L-lysine (PLL) and also lower price of PEI than PLL, this study was conducted to compare the efficacy of linear (LPEI) and branch (BPEI) forms of PEI with PLL as covering layers in fabrication of microcapsules. The microcapsules were fabricated using electrostatic bead generator and their shape/size, surface roughness, mechanical strength, and interlayer interactions were also investigated using optical microscopy, AFM, explosion test and FTIR, respectively. Furthermore, cytotoxicity was evaluated by comparing the two anionic final covering layers alginate (Alg) and sodium cellulose sulphate (NCS) using MTT test. BPEI was excluded from the rest of the study due to its less capacity to strengthen the microcapsules and also the aggregation of the resultant alginate-BPEI-alginate microcapsules, while LPEI showed properties similar to PLL. MTT test also showed that NCS has no superiority over Alg as final covering layer. Therefore, it is concluded that, LPEI could be considered as a more cost effective alternative to PLL and a promising subject for future studies. [ABSTRACT FROM AUTHOR]

Objectives: It has been shown that nifedipine cream 0.5% is effective in the treatment of anal fissure and in reducing facial wrinkles. However, no commercially manufactured formulation of this product is available in some countries and prescriptions for the medication need to be extemporaneously compounded by retail pharmacies. So, the aim of this study was to evaluate the quality of the compounded nifedipine cream 0.5%. Methods: Twenty‐one compounding pharmacies within Tehran area were randomly included in this study. A physician wrote the prescriptions for compounded nifedipine in dexpanthenol cream (0.5%) for fictitious patients, with two refills allowed per prescription. The extemporaneous products were analysed for potency and microbial limit using validated methods. Key findings: There was a significant variability both within and between pharmacies with respect to the potency of the compounded products. By contrast, no microbial contamination was detected in these products. Of 63 prescriptions, nifedipine concentration of 21 products (33.33%) was within ±20% of the prescribed dose. Thirty‐ nine (61.90%) were sub‐potent, which ranged in potency from 24.33–77.57%. One pharmacy provided products with essentially no nifedipine. Conclusion: Compounded nifedipine obtained from pharmacies in this study did not raise safety concerns when assessed for microbial contamination. However, compounded products may be misbranded, which may negatively impact the management of anal fissure and facial wrinkles. [ABSTRACT FROM AUTHOR]

Many herbs and spices have been recommended traditionally as galactagogues and several commercial formulations prepared using herbs. Due to the presence of various compounds such as polyphenols, flavonoids, isoflavones, and terpenes, bitter and stringent taste is elicited that make the consumption of these herbal preparations unpleasant. Moreover, these compounds are unstable when exposed to environmental conditions. In this regard, different approaches are used for taste masking such as microencapsulation. In the present study, microcapsules containing herbal galactagogue extract were developed through emulsification/ external gelation and Box-Behnken design was used to investigate the effects of independent variables (sodium alginate: 1-1.5%, calcium chloride: 0.2-1% and extract concentrations: 1-5%) on encapsulation efficiency (EE%). Following evaluation of the model, the optimum condition of encapsulation process was selected as 1.49% sodium alginate, 0.84 CaCl2, and 1.58% extract with EE% of 77.97%. Microcapsules had an acceptable spherical morphology and the results of Fourier transform-infrared spectroscopy (FTIR) revealed the presence of the extract within the microcapsules. The mean diameters of the uncoated and chitosan-coated microcapsules were 52 and 123 µm and encapsulation yield was 50.21 and 69.7%, respectively. The polydispersity index of 0.45 and 0.48 were an indicative of polydisperse nature of the microcapsules. The loss of flavonoids in microcapsules stored at two different temperatures was insignificant. The in-vitro release in simulated gastric fluid (SGF; pH 1.2) and simulated intestinal fluid (SIF; pH 7.4) were 48.1% and 80.11%, respectively during 24 h. The prepared extract-loaded microcapsules have potential to be used in matrices with neutral pH. [ABSTRACT FROM AUTHOR]

Antidepressant-like activity of T. kotschyanus has been recently reported by scientists but insufficient attention has been so far devoted to T. kotschyanus, and there is a lack of information on the other neurobehavioral effects and side effects of this species. In the current study, the anticonvulsant, anxiolytic, and sedative-hypnotic, effects of Thymus kotschyanus extract on male NMRI mice were evaluated using pentylenetetrazole, maximal electroshock, elevated plus maze, and pentobarbital-induced sleeping tests. Since phenolic compounds and flavonoids have main roles in pharmacological effects of most plant extracts, the phenolic and flavonoid contents of the extract were measured with Folin-Ciocalteu and AlCl3 reagents. Acute toxicity, passive avoidance, and open field tests were carried out to assess the toxicity of the extract. To find out the possible mechanism of action, flumazenil as the specific GABAA receptor antagonist was used. Anticonvulsant and hypnotic effects of the extract were observed at 400 and 600 mg/kg. The extract at the dose of 200 mg/kg revealed significant anxiolytic effects, but it did not show any adverse effects on learning and memory at all the tested doses. Results of this study indicate that Thymus kotschyanus extract has anticonvulsant, anxiolytic, and hypnotic effects, which are likely related to the ability of some phenolic compounds to activate α1-containing GABAA receptors but more experiments still need to be carried out in order to find the exact mechanism, active component, and the toxicity of the Thymus kotschyanus extract. [ABSTRACT FROM AUTHOR]

Ciprofloxacin is a commonly prescribed antibiotic for treatment of pulmonary infections. Nanocarriers such as nanomicelles can increase the drug residence time in the lungs and enhance their antibacterial effects. Dry powder inhalers (DPIs) are the preferred pulmonary drug delivery system and preparation of an optimum nanoaggregate from nanomicelles by means of spray drying would be valuable. The two-level full factorial design was performed in 16 runs. The effects of carrier type, anti-adhesion agent type, carrier to nanoparticle ratio and anti-adhesion agent to carrier ratio on the size of the microparticles, their in vitro pulmonary deposition, and redispersibility were investigated. Its antibacterial effects against Pseudomonas aeruginosa, Klebsiella pneumoniae, and Streptococcus pneumoniae also were investigated. All independent variables were fitted into two-factorial interaction models. The optimum nanoaggregate was prepared using mannitol and L-phenylalanine with a D0.5 of 1.7 µm and 60% fine particles. The process had no negative effect on the stability or drug release profile of the nanomicelles. The antibacterial effects of ciprofloxacin against microorganisms increased significantly. This spray drying process could be used for preparation of an optimum DPI from polymeric nanomicelles. This formulation could increase the efficacy of ciprofloxacin for treatment of pulmonary infections. [ABSTRACT FROM AUTHOR]

In this study a simple and reliable stability-indicating RP-HPLC method was developed and validated for analysis of Dexpanthenol in an artificial tear formulation. The chromatographic separation was performed on a HPLC C18 column (25.0 cm × 4.6 mm, 5 mm) using a mixture of 0.037 M monobasic potassium phosphate in water (adjusted with 0.1% (v/v) phosphoric acid to a pH of 3.2) and methanol (90:10). The flow rate was set at 1.5 mL/min and Dexpanthenol concentration was determined at λmax = 205 nm. The HPLC analysis method was validated in terms of linearity, precision, accuracy, specificity, and sensitivity according to International Conference on Harmonization (ICH) guidelines. The results indicated that the retention time was 8 min and no interferences were observed from the formulation excipients and stress degradation products. Linear regression analysis of data for the calibration plot showed a linear relationship between peak area and concentration over the range of 10 - 100 μg/mL; the regression coefficient was 0.996 and the linear regression equation was y = 20.011 x + 146.83. This HPLC method was precise and accurate in the range of 10 – 100 μg/mL. Also, the dexpanthenol concentration in artificial tear formulation was determined by this HPLC method, which was in accordance with the label claimed. This validated HPLC method could be used for routine analysis, quality control and the stability of analysis of eye gel containing dexpanthenol formulations. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate the effect of lipid structure on physicochemical properties of chitosan-fatty acid nanomicelles and prepare an optimum ciprofloxacin-loaded formulation from these conjugates which could enhance the antibacterial effects of drug against some important pathogens like P. aeruginosa. Significance: Nowadays, resistance in infectious diseases is a growing worldwide concern. Nanocarriers can increase the therapeutic index and consequently reduce the antibiotic resistance. By site-specific delivery of drug, the adverse effects of broad-spectrum antibiotics such as ciprofloxacin would be reduced. Methods: Fatty acid grafted chitosan conjugates were synthetized in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. The effects of fatty acid type (stearic acid, palmitic acid, and linoleic acid) on physicochemical properties of conjugates were investigated. Ciprofloxacin was encapsulated in nanomicelles by thin film hydration method. Also, the preparation process was optimized with a central compos- ite design. The antibacterial effect of optimum formulation against P. aeruginosa, K. pneumoniae, and S. pneumoniae species was determined. Results: All conjugates were synthetized with high yield values and the substitution degrees ranged between 2.13 and 35.46%. Ciprofloxacin was successfully encapsulated in nanomicelles. The optimum formulation showed high drug loading (≈19%), with particle size of about 260 nm and a sustained release profile of ciprofloxacin. The minimum inhibitory concentrations of ciprofloxacin in optimum formulation against P. aeruginosa and K. pneumoniae species were 4 and 2 times lower in comparison with the free drug, respectively. Conclusions: The antibacterial effect of ciprofloxacin was improved by encapsulation of drug in chitosan nanomicelles. [ABSTRACT FROM AUTHOR]

The methylotrophic yeast Pichia pastoris is a well-established expression host, which is often used in the production of protein pharmaceuticals. This work aimed to evaluate the effect of various concentrations of ascorbic acid in mixed feeding strategy with sorbitol/methanol on productivity of recombinant human growth hormone (r-hGH). The relevant concentration of ascorbic acid (5, 10, or 20 mmol) and 50 g/L sorbitol were added in batch-wise mode to the medium at the beginning of induction phase. The rate of methanol addition was increased stepwise during the first 12 h of production and then kept constant. Total protein and r-hGH concentrations were analyzed and the results compared with sorbitol/methanol feeding using one-way analysis of variance. Moreover, an effective clarification process using activated carbon was developed to remove process contaminants like pigments and endotoxins. Finally, a three-step chromatographic process was applied to purify the product. According to the obtained results, addition of 10 mmol ascorbic acid to sorbitol/methanol co-feeding could significantly increase cell biomass (1.7 fold), total protein (1.14 fold), and r-hGH concentration (1.43 fold). One percent activated carbon could significantly decrease pigments and endotoxins without any significant changes in r-hGH assay. The result of the study concluded that ascorbic acid in combination with sorbitol could effectively enhance the productivity of r-hGH. This study also demonstrated that activated carbon clarification is a simple method for efficient removal of endotoxin and pigment in production of recombinant protein in the yeast expression system. [ABSTRACT FROM AUTHOR]