Efficacy of simvastatin on wound healing and stem cell treatment, in addition to the cholesterol lowering mechanism, has been investigated in recent studies. In this study we have focused on ...formulation of tissue scaffolds comprised of mesenchymal stem cells and simvastatin loaded nanostructured lipid carriers (NLCs) dispersed in a polymeric matrix. These three dimensional and biodegradable systems were designed to bring a new perspective in treatment of diabetic wound. Therefore, NLC formulations containing simvastatin at the concentrations of 10% or 20% of lipid phase were prepared by high pressure homogenization technique. Simvastatin loaded NLC formulations were characterized with mean particle size of 158.15 ± 1.229 nm, PDI values lower than 0.17 and encapsulation efficiency above 99%. In-vitro release studies of simvastatin loaded NLC formulations were characterized by a high burst-release followed by sustained up to 12–24 h. Tissue scaffold formulations containing simvastatin loaded NLCs were prepared by freeze drying method. Cross-linked tissue scaffold formulations were prepared with 2:1 chitosan:collagen polymer ratio and 2-fold concentrated NLC formulation, having a three-dimensional structure with porosity value of 74.38%, pore size distribution within 20–200 μm, 710.88% high water absorption capacity, 57.7% weight loss and suitable mechanical strength for in-vivo studies. Incorporation of NLCs into tissue scaffolds decreased the initial simvastatin burst release ratio and provided controlled release profile. Tissue scaffolds containing simvastatin lipid nanoparticles increased wound closure rate, promoted vascularization of injured tissue and enhanced viability and proliferation of stem cells. Thereupon, tissue scaffold formulation containing simvastatin lipid nanoparticles and stem cells together provided effective wound healing with increased epithelialization, proliferation and vascularization.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Drug delivery for neuroprotection/neuroregeneration after traumatic peripheral nerve injuries still remains a challenge. For this purpose, we formulated composite nanofiber formulation for the dual ...local delivery of alpha lipoic acid (ALA) and atorvastatin (ATR) to enhance regeneration process after peripheral nerve injury. The initial stage involved encapsulation of ATR into nanosprayed chitosan (CH) nanoparticles after which the CH nanoparticles were embedded into poly(lactic-co-glycolic acid) (PLGA) nanofibers containing freely dispersed ALA within the fiber structure. Morphology investigations revealed that smooth and randomly aligned nanofibers with mean diameter of 340±69 nm were formed. Encapsulation efficiency for ALA and ATR were calculated as 92.76±3.53 % and 89.27±5.053 %, respectively. Differential Scanning Calorimetry and FT-IR analysis confirmed successful encapsulation of ALA and ATR into the composite nanofibers; however, XRD results indicated surface localization of ALA within the structure. Porosity and pore volume of the nanofibers increased in accordance with increase in density of the electrospunned solution. Similarly, mechanical strength of the nanofibers was found to increase significantly following the incorporation of ALA and ATR with respect to the unloaded nanofibers (p<0.05). Dual release of ALA and ATR in different fashions was confirmed by
in-vitro
release test of the nanofibers. For ALA, an immediate release percentage of 83.90 % within the first hour was observed. On the other hand, ATR exhibited a three-stage release profile which begins with a relatively lower initial release (22.07 %) in comparison to ALA followed by an increasing release (82.439%) up to 150 h. According to cell viability results, blank and loaded formulations were found to have no cytotoxic effect on both L-929 and B35 cell lines after incubation for up to 48 h. Based on this, composite PLGA nanofibers could be classified as suitable candidates for long-term and local delivery of neuroprotective drugs in peripheral nerve injury.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The objective of this study was to develop polysorbate 80 coated and Atorvastatin loaded poly(lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles and to investigate ...advantages of coating on nanoparticles for brain delivery of Atorvastatin. The nanoparticles were prepared by nanoprecipitation method. The effects of polymer concentration, PEG content and polysorbate 80 coating on the particle size, drug loading efficiency and release behaviour of nanoparticles were investigated. Additionally, cellular uptake and brain targeting of formulated nanoparticles were studied. Particle sizes were in the range of 30-172 nm depending on formulation parameters. Increasing the polymer concentration significantly increased the nanoparticle size. Decreasing the PEG content from 15% to 5% (w/w) in polymer composition increased the nanoparticle size from 69 to 172 nm. Both coated and uncoated polysorbate 80 nanoparticles were effectively internalised within the endothelial cells. Moreover, both types of nanoparticles were able to penetrate the blood brain barrier and reach the maximum in brain 1 h post injection. It was concluded that these nanoparticles are promising nanosystems for treatment of neurological disorders.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Many studies have been done in the literature on perforations due to substance abuse, and there are limited publications on perforations related to inhaled methamphetamine. Recently, in our clinic, ...we observed an increase in the number of patients with perforated peptic ulcer, which we think is secondary to a significant increase in the consumption of this drug. The main purpose of this study is to determine whether the use of inhaled methamphetamine known as 'fire and ice' is a factor directly related to peptic perforation and its complications and also to determine the demographic variables of patients with peptic ulcer perforation due to this substance use, in the context of the literature.
A retrospective study was conducted by examining the medical records of 29 gastric perforation patients who underwent surgical treatment in our clinic in 2021. Data were transferred to SPSS.23 (IBM Inc., Chicago, IL, USA) program and evaluated with statistical analysis. Normality assumptions of continuous variables were examined with Kolmogorov-Smirnov test, and variance homogeneity was examined with Levene's test. Bi-level comparisons, t-test if the data are normally distributed and Mann-Whitney U-test for bi-level comparisons where the data are not normally distributed were used. Relationships between categorical variables were examined by Chi-square test analysis. P<0.05 was accepted as the level of significance in all analyzes.
Twenty-nine patients were divided into two groups as methamphetamine users (n=13) and non-users (n=16). There was a statistically significant difference according to the lower age in the group using methamphetamine (31.69-48.8-P=0.025). The pres-ence of PU history differed significantly between the groups (P=0.009). Interestingly, aspartate transaminase alanine aminotransferase values were lower in substance dependents (P=0.020). Furthermore, there was a significant difference in localization between groups (P<0.001). There was no statistically significant difference between the two groups in terms of gender, clinical presentation, and other laboratory values.
Methamphetamine consumption, known as fire and ice, is an important risk factor for ulcer development and subsequent perforation, especially in young patients and long-term consumption of this narcotic substance. It has been determined that this risk factor, which is currently considered rare, has been seen in a very large number in a short time in our clinic. The use of this substance, which is considered a major social threat, is becoming more and more widespread, and this study is only a small part of the iceberg reflected in the general surgery clinic of a hospital.
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Despite the new treatment strategies within the last 30 years, peripheral nerve injury (PNI) is still a worldwide clinical problem. The incidence rate of PNIs is 1 in 1000 individuals ...per year. In this study, we designed a composite nanoplatform for dual therapy in peripheral nerve injury and investigated the in-vivo efficacy in rat sciatic nerve crush injury model. Alpha-lipoic acid (ALA) was loaded into poly lactic-co-glycolic acid (PLGA) electrospun nanofibers which would release the drug in a faster manner and atorvastatin (ATR) loaded chitosan (CH) nanoparticles were embedded into PLGA nanofibers to provide sustained release. Sciatic nerve crush was generated via Yasargil aneurism clip with a holding force of 50 g/cm2. Nanofiber formulations were administered to the injured nerve immediately after trauma. Functional recovery of operated rat hind limb was evaluated using the sciatic functional index (SFI), extensor postural thrust (EPT), withdrawal reflex latency (WRL) and Basso, Beattie, and Bresnahan (BBB) test up to one month in the post-operative period at different time intervals. In addition to functional recovery assessments, ultrastructural and biochemical analyses were carried out on regenerated nerve fibers. L-929 mouse fibroblast cell line and B35 neuroblastoma cell line were used to investigate the cytotoxicity of nanofibers before in-vivo experiments. The neuroprotection potential of these novel nanocomposite fiber formulations has been demonstrated after local implantation of composite nanofiber sheets incorporating ALA and ATR, which contributed to the recovery of the motor and sensory function and nerve regeneration in a rat sciatic nerve crush injury model.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Celecoxib (CXB) is a Biopharmaceutical Classification System (BCS) Class II molecule with high permeability that is practically insoluble in water. Because of the poor water solubility, there is a ...wide range of absorption and limited bioavailability following oral administration. These unfavorable properties can be improved using dry co-milling technology, which is an industrial applicable technology. The purpose of this study was to develop and optimize CXB nanoformulations prepared by dry co-milling technology, with a quality by design approach to maintain enhanced solubility, dissolution rate, and oral bioavailability. The resulting co-milled CXB composition using povidone (PVP), mannitol (MAN) and sodium lauryl sulfate (SLS) showed the maximum solubility and dissolution rate in physiologically relevant media. Potential risk factors were determined with an Ishikawa diagram, important risk factors were selected with Plackett-Burman experimental design, and CXB compositions were optimized with Central Composite design (CCD) and Bayesian optimization (BO). Physical characterization, intrinsic dissolution rate, solubility, and stability experiments were used to evaluate the optimized co-milled CXB compositions. Dissolution and permeability studies were carried out for the resulting CXB nanoformulation. Oral pharmacokinetic studies of the CXB nanoformulation and reference product were performed in rats. The results of in vitro and in vivo studies show that the CXB nanoformulations have enhanced solubility (over 4.8-fold (8.6 ± 1.06 µg/mL vs. 1.8 ± 0.33 µg/mL) in water when compared with celecoxib pure powder), and dissolution rate (at least 85% of celecoxib is dissolved in 20 min), and improved oral pharmacokinetic profile (the relative bioavailability was 145.2%, compared to that of Celebrex
, and faster t
3.80 ± 2.28 h vs. 6.00 ± 3.67 h, indicating a more rapid absorption rate).
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The main objective of this study was to evaluate the pharmacokinetics of ritonavir (RTV) nanosuspension in rats in both fed and fasted state in comparison with coarse powder, physical mixture and ...commercial product (Norvir®). The point to point relation model was generated between the results of in vitro dissolution and in vivo pharmacokinetic studies. The oral RTV nanosuspension was prepared with microfluidization method. Nanosuspension was obtained with 540–550 nm of particle size, 0.1–0.4 of particle size distribution and about −20 mV of zeta potential values. According to in vivo pharmacokinetic studies in rats, Cmax and AUC0−t values in nanosuspension displayed an 8.9- and 12.5-fold increase compared to the coarse powder, and a 1.9- and 2.1-fold increase compared to the commercial product, respectively in the fed group. The point to point relation model showed that the correlation model was significant. It is concluded that nanosuspension is a promising drug delivery system to enhance oral bioavailability of ritonavir.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZRSKP
Antibacterial nanofibers have a great potential for effective treatment of infections. They act as drug reservoir systems that release higher quantities of antibacterial agents/drug in a controlled ...manner at infection sites and prevent drug resistance, while concomitantly decreasing the systemic toxicity. With this drug delivery system, it is also possible to achieve multiple drug entrapment and also simultaneous or sequential release kinetics at the site of action. Therefore, advances in antibacterial nanofibers as drug delivery systems were overviewed within this article. Recently published data on antibacterial drug delivery was also summarised to provide a view of the current state of art in this field. Although antibacterial use seems to be limited and one can ask that 'what is left to be discovered?'; recent update literatures in this field highlighted the use of nanofibers from very different perspectives. We believe that readers will be benefiting this review for enlightening of novel ideas.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In this study, a simple, rapid, cost-effective, and sensitive reversed-phase high-performance liquid chromatographic method has been developed and validated for the analysis of moxifloxacin in ...plasma. The chromatographic separation was achieved on a Zorbax Eclipse XDB-C18 column (150 mm x 4.6 mm i.d.) connected to a Phenomenex C(18) column (4 mm x 3.0 mm i.d.) using a mixture of acetonitrile: 15 mM citrate buffer (pH 3) (23:77, v/v) as the mobile phase with isocratic system at a flow rate of 1 mL/min. Fluorescence detection was employed with excitation at 290 nm and emission at 500 nm. Lomefloxacin was used as internal standard. Plasma samples were prepared with addition of acetonitrile only. The method was fully validated according to the International Conference on Harmonization (ICH) guidelines. The results of the validation parameters were: linearity range, 3-6000 ng/mL (R(2) = 0.9994); mean recovery, 100.48 %; limit of quantification, 5 ng/mL; limit of detection, 1 ng/mL; and intra- and inter-day precision less than 3.2% and 5.1%, respectively. The robustness of the method was evaluated and confirmed with fractional factorial design. After validation studies, the method was applied in order to conclude the effects of pregnancy on postoperative pharmacokinetic profiles of moxifloxacin. For this aim, moxifloxacin was given to non-pregnant women (n=9) and caesarean-sectioned women (n=6) as a single intravenous dose (400 mg Avelox(R) infusion). Plasma samples were analyzed in order to compare pharmacokinetic profiles of pregnants and non-pregnants. Peak serum concentrations of non-pregnant and caesarean-sectioned women at the arterial port after the infusion were 4.95 +/- 1.50 and 1.56 +/- 0.16 microg/mL, respectively. The mean elimination half-life, volume of distribution and calculated area under the concentration-time curve (AUC)(0-infinity) were 5.54 +/- 0.73 h, 65.58 +/- 6.30 L and 49.95 +/- 6.30 microg.h/mL for non-pregnant women and 3.50 +/- 0.37 h, 215.85 +/- 24.87 L and 10.53 +/- 0.66 microg.h/mL for caesarean-sectioned women, respectively. These results indicated that pregnancy has a significant effect on the pharmacokinetics of moxifloxacin.
The radioactivity concentrations of nuclides (238)U, (232)Th and (40)K in lake sediments collected from 15 different stations at Altınkaya dam lake and 12 different stations at Derbent dam lake in ...Turkey were measured using high-resolution gamma-ray spectrometry. The measurement was done using a coaxial HPGe detector system coupled to the Ortec-Dspect jr digital MCA system. The average measured activity concentrations of the nuclides (238)U, (232)Th and (40)K were found to be 19.5, 27.7 and 460 Bq kg(-1) in Altınkaya dam, whereas the activity concentrations were 18.8, 25.5 and 365 Bq kg(-1) in Derbent dam, respectively. The measured activity concentrations in the present study have been compared with similar measurements from different locations in the world.
