Levent Oner

A comparative study of treatment for brain edema: Magnesium sulphate versus dexamethasone sodium phosphate

Treatments for brain edema are important and one of the major options is corticosteroids. Cell membrane stabilization and prevention of formation of free radicals are the main mechanisms of action of steroids in edema treatment. As an alternative therapeutic agent, magnesium sulphate has been used for its neuroprotective effect in various injury models. In our animal model of brain injury, cold has been used in Sprague-Dawley rats. After brain injury, magnesium sulphate (600 mg/kg) or dexamethasone sodium phosphate (0.2 mg/kg) were administered to experimental groups. The degree of brain edema and lipid peroxidation was evaluated using the wet-dry weight method, the determination of malondialdehyde (MDA) levels and an ultrastructural grading system. Magnesium sulphate treatment was found to be the most effective choice due to the absence of side effects and comparable efficacy to corticosteroids.

Atorvastatin efficiency after traumatic brain injury in rats

BACKGROUND The neuroprotective effects of statins possibly depend on their pleiotropic effect such as antioxidative and anti-inflammatory properties. In this study, we have evaluated the efficiency of atorvastatin on brain edema, lipid peroxidation, and ultrastructural changes in TBI animal model. METHODS Modified Feeney method has been used for the trauma model in rats. Only craniectomy for group A and trauma after craniectomy for group B was the procedure for animals. For the trauma, rods weighing 24 g were dropped on a foot plate just over the dura. Atorvastatin (1 mg/kg, IP) was administered to the animals in group C after craniectomy and trauma; but on the other hand, animals in group D received only 0.5 mL PEG as the vehicle. Brains were harvested 24 hours after the trauma for the assays of wet-dry weight, lipid peroxidation level, and ultrastructural investigations. Lipid peroxidation levels, TEM, and UNGS were the investigated parameters. The statistical comparisons between the groups were investigated by 1-way ANOVA and post hoc analysis by Duncan and Dunnett T3 test within the groups at the significance level P = .05. RESULTS Trauma increased water contents of the brain tissues and lipid peroxidation levels in groups B and D. When compared with the results of group B (brain edema, 84.694% +/- 1.510%; lipid peroxidation, 74.932 +/- 2.491 nmol/g tissue), atorvastatin (1 mg/kg) significantly decreased brain edema (77.362% +/- 1.448%), lipid peroxidation level (58.335 +/- 3.980 nmol/g tissue), and UNGS scores in group C (P < 0.05). CONCLUSION In this descriptive study, the remarkable improvements of atorvastatin on brain edema, lipid peroxidation, and ultrastructural investigations encouraged us for a further dose optimization study.

Design and optimization of novel paclitaxel-loaded folate-conjugated amphiphilic cyclodextrin nanoparticles.

As nanomedicines are gaining momentum in the therapy of cancer, new biomaterials emerge as alternative platforms for the delivery of anticancer drugs with bioavailability problems. In this study, two novel amphiphilic cyclodextrins (FCD-1 and FCD-2) conjugated with folate group to enable active targeting to folate positive breast tumors were introduced. The objective of this study was to develop and characterize new folated-CD nanoparticles via 3(2) factorial design for optimal final parameters. Full physicochemical characterization studies were performed. Blank and paclitaxel loaded FCD-1 and FCD-2 nanoparticles remained within the range of 70-275nm and 125-185nm, respectively. Zeta potential values were neutral and -20mV for FCD-1 and FCD-2 nanoparticles, respectively. Drug release studies showed initial burst release followed by a longer sustained release. Blank nanoparticles had no cytotoxicity against L929 cells. T-47D and ZR-75-1 human breast cancer cells with different levels of folate receptor expression were used to assess anti-cancer efficacy. Through targeting the folate receptor, these nanoparticles were efficiently engulfed by the breast cancer cells. Additionally, breast cancer cells became more sensitive to cytotoxic and/or cytostatic effects of PCX delivered by FCD-1 and FCD-2. In conclusion, these novel folate-conjugated cyclodextrin nanoparticles can therefore be considered as promising alternative systems for safe and effective delivery of paclitaxel with a folate-dependent mechanism.

Chitosan Formulations for Steroid Delivery: Effect of Formulation Variables on In Vitro Characteristics

ABSTRACT Chitosan film formulations for steroid delivery after craniomaxillofacial surgery were formulated by using three different types of chitosan with respect to their molecular weight as low, medium and high. Film formulations were prepared by casting/solvent evaporation technique. In vitro characterization, film thickness, equilibrium swelling degree, in vitro release profiles and surface morphologies were investigated. For two different types of crosslinkings, the release of dexamethasone sodium phosphate (DSP) can be extended as the molecular weight increases. As a result, chitosan film formulations should be beneficial for steroid delivery for a certain time after craniomaxillofacial surgery.

Systematic development of pH-independent controlled release tablets of carvedilol using central composite design and artificial neural networks

The purpose of this study was to apply the optimization method incorporating artificial neural network (ANN) using pH-independent release of weakly basic drug, carvedilol from HPMC-based matrix formulation. Because of weakly basic nature of carvedilol, drug shows pH-dependent solubility. The enteric polymer EUDRAGIT L100 was added formulations to overcome pH-dependent solubility of carvedilol. Effects of the Hydroxypropylmethyl cellulose (HPMC) K4M and EUDRAGIT L100 amount on drug release were investigated. For this purpose 13 kinds of formulations were prepared at three different levels of each variables. The optimization of the formulation was evaluated by using ANN method. Two formulation parameters, the amounts of HPMC K4M and Eudragit L100 at three levels (−1, 0, 1) were selected as independent/input variables. In-vitro dissolution sampling times at twelve different time points were selected as dependent/output variables. By using experimental dissolution results and amount of HPMC K4M and EUDRAGIT L100, percentage of dissolved carvedilol was predicted by ANN. Similarity factor (f2) between predicted and experimentally observed profile was calculated and f2 value was found 76.33. This value showed that there was no difference between predicted and experimentally observed drug release profile. As a result of these experiments, it was found that ANNs can be successfully used to optimize controlled release drug delivery systems.

Phenytoin Sodium Microcapsules: Bench Scale Formulation, Process Characterization and Release Kinetics

The objective of this investigation was to formulate and prepare sustained-action microcapsules of phenytoin sodium (diphenyl hydantoin sodium salt). Using ethylcellulose and methyl acrylic acid copolymers (Eudragit S-100 and L-100) as coating materials, microcapsules of phenytoin sodium were formulated by an organic phase separation and a granule coating method. The phase diagrams were used to study the phase separation in an ethylcellulose-petroleum ether-toluene system, and the effect of temperature and amount of petroleum ether on the ethylcellulose left in the organic solvent mixture was investigated. The phase diagrams showed that increase in temperature did not significantly affect the ethylcellulose residue, and 60 ml of nonsolvent was found adequate for microencapsulation. In vitro release of the formulated microcapsules and the commercially available preparations was performed in CO2-free distilled water using the USP XXIII rotating basket method, and the profiles were evaluated by Higuchi kinetics. Geometric mean diameters of the microparticles prepared by two different methods showed differences due to different core:wall ratios. A 4 x 5 factorial design was utilized and multiple regression was applied to the dependent variables (ethylcellulose content, percent dissolved) against the independent variables (amount of nonsolvent, temperature, core:wall ratio); the optimum phenytoin sodium-to-ethylcellulose ratio was 1:2.3. Utilizing second-order polynomial equations, response-surface graphs and contour plots pointed out the time necessary for 40%, 55%, and 70% release of phenytoin sodium. The desired release profiles were obtained with formulations E-5, ES-2 and ESL-2.

Studies on the Microencapsulation of Dextropropoxyphene Hydrochloride. Part 1. Preparation by Coacervation and the in Vitro Evaluation.

AbstractThe main purpose of our study is to achieve the release at a slower rate and the prolonged action of dextropropoxyphene hydrochloride through microencapsulation. Besides this, microencaosulation of this active agent can prevent the incomnatibility in the presence of aspirin, and the local anesthetic effecton the tongue.Microcapsules o f dextropropoxyphene hydrochloride (D-PRX-HCl) were prepared by coacervation method with core-shell ratios of 1:1 and 1:2, and the invitrorelease rate experiments were carried on in 0.1 N hydrochloric acid solution.

Preparation and characterization of nimesulide containing nanocrystal formulations.

The aim of this study was to develop and characterize nanocrystal formulation containing nimesulide. Physical mixture of drug and excipient (nimesulide:pluronic F127, 1:0.5) was also prepared to compare the efficiency of formulations. The physicochemical characteristics of the formulations were determined by means of Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and X-ray diffractometry. Particle size, saturation solubilities as a function of pH, and permeability across Caco-2 monolayers were determined for nimesulide in powder, physical mixture, and nanocrystal formulations. In FT-IR analysis, the characteristic peaks that belong to nimesulide were seen in all formulations. X-ray diffractograms displayed that crystalline structure of nimesulide was conserved in the nanocrystal formulation. The interaction between nimesulide and pluronic F127 was demonstrated by DSC analysis. In all conditions, the average particle size of the nanocrystal formulations decreased significantly (p < 0.05) as compared with nimesulide and physical mixture. The solubility of nimesulide in nanocrystal formulation was higher than those of nimesulide in powder and physical mixture. Permeability studies revealed that nimesulide is a highly permeable compound whether in powder form or in physical mixture and nanocrystal formulation. All these results clearly demonstrate that aqueous solubility of poorly water-soluble compounds can be improved by preparing nanocrystal formulations.

Dry powders for the inhalation of ciprofloxacin or levofloxacin combined with a mucolytic agent for cystic fibrosis patients

Abstract Objective: This study aimed to design and characterize an inhalable dry powder of ciprofloxacin or levofloxacin combined with the mucolytics acetylcysteine and dornase alfa for the management of pulmonary infections in patients with cystic fibrosis. Methods: Ball milling, homogenization in isopropyl alcohol and spray drying processes were used to prepare dry powders for inhalation. Physico-chemical characteristics of the dry powders were assessed via thermogravimetric analysis, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry and scanning electron microscopy. The particle size distribution, dissolution rate and permeability across Calu-3 cell monolayers were analyzed. The aerodynamic parameters of dry powders were determined using the Andersen cascade impactor (ACI). Results: After the micronization process, the particle sizes of the raw materials significantly decreased. X-ray and DSC results indicated that although ciprofloxacin showed no changes in its crystal structure, the structure of levofloxacin became amorphous after the micronization process. FT-IR spectra exhibited the characteristic peaks for ciprofloxacin and levofloxacin in all formulations. The dissolution rates of micro-homogenized and spray-dried ciprofloxacin were higher than that of untreated ciprofloxacin. ACI results showed that all formulations had a mass median aerodynamic diameter less than 5 μm; however, levofloxacin microparticles showed higher respirability than ciprofloxacin powders did. The permeability of levofloxacin was higher than those of the ciprofloxacin formulations. Conclusion: Together, our study showed that these methods could suitably characterize antibiotic and mucolytic-containing dry powder inhalers.

Localized delivery of methylprednisolone sodium succinate with polymeric nanoparticles in experimental injured spinal cord model

Abstract With important social and economic consequences, spinal cord injuries (SCIs) still exist among major health problems. Although many therapeutic agents and methods investigated for the treatment of acute SCI, only high dose methylprednisolone (MP) is being used currently in practice. Due to the serious side effects, high dose systemic MP administration after SCI is a critical issue that is mostly considered controversial. In our study, it is aimed to develop a nanoparticle-gel combined drug delivery system for localization of MP on trauma site and eliminating dose-dependent side effects by lowering the administered dose. For this purpose, methyl prednisolone sodium succinate (MPSS) loaded polycaprolactone based nanoparticles were developed and embedded in an implantable fibrin gel. The effects of MPSS delivery system are evaluated on an acute SCI rat model, by quantification the levels of three inflammatory cytokines (interleukin-1β, interleukin-6 and caspase-3) and assessment of the damage on ultrastructural level by transmission electron microscopy. Developed NP-gel system showed very similar results with systemic high dose of MPSS. It is believed that developed system may be used as a tool for the safe and effective localized delivery of several other therapeutic molecules on injured spinal cord cases.