Design and characterization of nanocarriers loaded with Levofloxacin for enhanced antimicrobial activity; physicochemical properties, in vitro release and oral acute toxicity

Inorganic and carbon based nanomaterials are widely used against several diseases, such as cancer, autoimmune diseases as well as fungi and bacteria colonization. In this work, Santa Barbara Amorphous mesoporous silica (SBA), Halloysite Nanotubes (HNTs) and Multiwalled Carbon Nanotubes (CNTs) were loaded with fluoroquinolone Levofloxacin (LVF) to be applied as antimicrobial agents. The prepared via adsorption nanocarriers were characterized by Fourier-Transformed Spectroscopy, Scanning Electron Microscopy as well as High Pressure liquid Chromatography. In vitro release studies were carried out using Simulated Body Fluid at 37o C and data analyzed by various kinetic models showing slow dissolution over 12-24 hours. Antimicrobial studies showed improved antibacterial activity against Escherichia coli, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, and Staphylococcus epidermidis compared to neat nanomaterials. CNTs were found to be the most promising candidates for LVF delivery and they were chosen to be further studied for their acute oral toxicity and histopathological examination using C57/Black mice. Histological examination depicted that drug loading did not affect mice organs morphology as well as hepatocyte degeneration, central vein degeneration and parenchymal necrosis scores. To conclude, the prepared nanomaterials present significant characteristics and can act as antimicrobial drug carriers; CNTs found to be safe candidates when orally fed to mice

Traditional herbal drugs against liver diseases – Experimented in vitro using HepG2 cells for induced steatosis

Salvia fruticosa leaves, Malva sylvestris flowers, Taraxacum officinale aerial parts, Plantago ovata seeds, Tanacetum parthenium aerial parts, and Allium sativum bulbs are documented for traditional use against hepatic disorders and different liver diseases. To evaluate herbal drug material for potential use against liver diseases, at molecular level for the efficacy linked to ethnobotanical documented data.Different herbal extracts were prepared and standardized by HPLC, according to European Pharmacopoeia. Initially 0.25 mg/mL each standardized extract was applied to oleic+palmitic acid induced fatty liver using a HepG2 cell culture model. ALT, AST, GSH, and MDA levels were comparatively analyzed, in addition to cell Nil Red staining. The highest activity for MDA reduction was observed for the A. sativum extract at 48.2% level, followed by 36.4% for M. sylvestris, and S. fruticosa extracts with 27.3% reduction, respectively. Glutathione levels increased to 59.1% when A. sativum extract was applied. M. sylvestris extract increased the glutathione levels in the medium by 49.7%; S. fruticosa extract decreased ALT levels by 53.5% and M. sylvestris extract by 38.5%, whereas the standard resveratrol reduced ALT level by 30.9%, respectively. The AST levels for M. sylvestris extract was 46.5%, compared to resveratrol by 93%. A. sativum, M. sylvestris, and S. fruticosa standard extracts showed relatively good correlation and activity where further in vivo studies should be performed

Hypoglycemic activity of Capparis ovata desf. var. palaestina zoh. methanol extract

Caper (Capparis ovata Desf. and Capparis spinosa L.) is naturally widespread in Turkey. Traditionally, buds, fruits, seeds and roots of this plant are used as tonic, diuretic, anti-rheumatic, expectorant, antidiabetic, and antifungal. The aim of this study is to evaluate potential hypoglycemic effect of C. ovata var. palaestina extracts in alloxan-induced diabetic mice. For this purpose; diabetic mice were administered with 100, 300, 500 mg/kg (i.p.) doses of methanol extract of bud and fruit. Blood glucose levels were screened 60, 120, 240 and 360 min. after treatment. Furthermore, high resolution mass spectrometry (HRMS) analysis, ABTS and DPPH free radical scavenging activity test, and phenolic and flavonoid compounds analysis of extracts were carried out. The data obtained from in vivo study revealed that fruit-methanol 500 mg/kg (FM3), bud-methanol 300 mg/kg (BM2), bud-methanol 500 mg/kg (BM3) extracts showed significant hypoglycemic activity. All extracts indicated significant antioxidant activity, however bud-methanol (BM) extract demonstrated the most potent antioxidant activity. Moreover high levels of phenolic substances and flavonoids were involved in all extracts, but the highest levels were found in FM extract. HRMS study showed that rutin, quercetin 3-O-glucoside (isoquercitrin) and stachydrine substances had seen in BM extract. The results of this study showed that the C. ovata var. palaestina extracts which, indicate hypoglycemic, antioxidant activities, might provide additional support in diabetes

A novel approach for skin infections: Controlled release topical mats of poly (lactic acid)/poly(ethylene succinate) blends containing Voriconazole

WOS: 000438500700010The oral and injectable formulations of Voriconazole (VRZ), a known antifungal agent with low solubility, seem to cause severe side effects. Consequently, topical application of VRZ could be advantageous for skin fungal infections. In this study, VRZ embedded in a polymeric matrix composed of biocompatible poly(lactic acid) (PLA) and poly(ethylene succinate) (PESu). The mats were prepared via solvent evaporation and fully characterized by Fourier-Transformed Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), in vitro hydrolysis and release studies. The prepared blends defined as immiscible by DSC and SEM while FTIR spectroscopy did not disclose noticeable interactions between the polymers. It was found that hydrolysis was improved by increasing PESu content into the blend. VRZ loaded blends spectra exhibit slight differentiation compared to neat blends while the absence of VRZ melting peak, as DSC illustrated, indicated drug amorphization. Lastly, in vitro release studies depicted a controlled release pattern dependent on mats' hydrolysis degree. An improved antifungal activity of mats was detected by disc diffusion method against various microorganisms. Ex vivo studies of VRZ did not determine high permeation while histopathology results using mice were profitable. The irritation experiments displayed that the mats did not induce any skin irritation

Effects of vincamine on testicular dysfunction in alloxan-induced diabetic male rats

Background: Diabetes mellitus (DM) is frequently linked with problems of several organ systems, including retinopathy, neuropathy, and nephropathy. Additionally, patients have changes in sexual functioning, such as decreased libido and fertility. Vincamine, a monoterpenoid indole alkaloid, has hypoglycemic and antioxidant effects. Objectives: This research assessed the impact of vincamine on testicular dysfunction in alloxan-induced male rats by measuring fasting blood glucose, oxidative stress, seminal analysis, and histological examination of the testis. Methods: Wister-albino male rats were randomized into the following groups at random: Untreated-healthy, untreated-DM, vincamine-treated (20 mg/kg) DM, vincamine-treated (40 mg/kg) DM, and clomiphene-treated DM (5 mg/kg). On day 14, rats were sacrificed, and semen/blood samples were collected. Sperm count, motility, and morphological abnormalities were noted by microscopic examination. The testis was examined histopathologically and assessed using Johnsen’s score. Results: Compared with the untreated diabetic group, a dosage of 40 mg/kg vincamine generate a significant reduction in fasting blood sugar (FBG). Compared with the untreated diabetic group, the vincamine-treated rats produced greater plasma testosterone levels and Johnsen scores. In the vincamine 20 mg/kg group, sperm concentration was higher than in the vincamine 40 mg/kg group. Conclusions: It is possible that vincamine has a potential preventive effect against diabetes-related reproductive problems attributable to its antioxidant activity and capacity to restore testicular steroidogenesis

Protein and gene delivery systems for neurodegenerative disorders: Where do we stand today?

It has been estimated that every year, millions of people are affected by neurodegenerative disorders, which complicate their lives and their caregivers’ lives. To date, there has not been an approved pharmacological approach to provide the complete treatment of neurodegenerative disorders. The only available drugs may only relieve the symptoms or slow down the progression of the disease. The absence of any treatment is quite rational given that neurodegeneration occurs by the progressive loss of the function or structure of the nerve cells of the brain or the peripheral nervous system, which eventually leads to their death either by apoptosis or necrotic cell death. According to a recent study, even though adult brain cells are injured, they can revert to an embryonic state, which may help to restore their function. These interesting findings might open a new path for the development of more efficient therapeutic strategies to combat devastating neurodegenerative disorders. Gene and protein therapies have emerged as a rapidly growing field for various disorders, especially neurodegenerative diseases. Despite these promising therapies, the complete treatment of neurodegenerative disorders has not yet been achieved. Therefore, the aim of this review is to address the most up-to-date data for neurodegenerative diseases, but most importantly, to summarize the available delivery systems incorporating proteins, peptides, and genes that can potentially target such diseases and pass into the blood–brain barrier. The authors highlight the advancements, at present, on delivery based on the carrier, i.e., lipid, polymeric, and inorganic, as well as the recent studies on radiopharmaceutical theranostics

Recent Advancements in Apoptosis-Based Therapeutic Approaches for Cancer Targeting

Apoptosis, known as programmed cell death, has been considered a potent target for the pharmacy industry. The scientific community has actively participated to research which evaluate active molecules for possible inhibition or induction of apoptosis. Nanocarriers especially for cancer targeting are widely found through literature; they mainly based on inorganic, lipid or polymer nanoparticles which incorporate anticancer drugs. Another important and innovative category of anticancer agents is that of microRNAs. In this chapter, a discussion about the most recent applications of apoptosis-based agents mainly focusing on cancer target is done

Yabanmersini (vaccinium myrtillus l.) meyve özü'nün mide kanseri, ags hücre hattı üzerinde antioksidan aktivitesi ve anti-kanser etkileri

Objective: Vaccinium myrtillus L. fruits are consumed as food. This research was aimed to evaluate V. myrtillus methanol extract antioxidant and cytotoxic activities and determine its anti-cancer potential to further study against gastric cancer. Material and Method: V. myrtillus fruit (Bilberry) methanol extract was examined for its antioxidant activities by ABTS•+ and DPPH• assays. The phytochemical analysis of the extract was studied by HPLC method. The cytotoxic effect of V. myrtillus fruit methanol extract on gastric cancer cell line AGS was measured by Cell Titer-Glo assay. Additionally, as healthy control, fibroblast like human mesenchymal stem cell line was used for testing anti-cancer efficacy. Result and Discussion: V. myrtillus fruit methanol extract showed 0.1413 and 0.0439 mg/mL IC50 values as antioxidant activity by ABTS•+ and DPPH• assays, respectively. Malvidin-3-O-Glucoside was detected as an anthocyanin compound by HPLC method. Cytotoxicity analysis showed that among different concentrations (0.5-10 mg/ml), the most significantly, 2 mg/ml of Bilberry extract treatment decreased the viability of AGS gastric cancer cells while sparing healthy MSC cells. This data suggests the further analysis of Bilberry extract on several cancer cell lines as well as the determination of a potential active substance in the extract.Amaç: Vaccinium myrtillus L. meyvesi Türkiye’de gıda olarak tüketilmektedir. Bu araştırma V. myrtillus metanol ekstresinin antioksidan ve sitotoksisite aktivitelerini ve mide kanser hücresindeki potansiyel etkilerini belirlemeyi amaçlamıştır. Gereç ve Yöntem: V. myrtillus meyvesi metanol ekstresinin antioksidan aktiviteleri spektrofotometrik olarak ABTS+ ve DPPH• yöntemleriyle gerçekleştirilmiştir. Fitokimyasal analiz HPLC yöntemi ile araştırılmıştır. V. myrtillus metanol ekstresinin mide kanseri hücre hattı AGS üzerindeki sitotoksik etkisi, Cell Titer-Glo testi ile ölçülmüştür. Ek olarak, anti-kanser etkinlik analizi için fibroblast benzeri insan mezenkimal kök hücre hattı sağlıklı kontrol hücreleri olarak kullanılmıştır. Morfolojik değişiklikler, faz kontrast mikroskobu kullanılarak incelenmiştir. Sonuç ve Tartışma: V. myrtillus meyve metanol ekstresinde ABTS+ ve DPPH• testleri ile sırasıyla 0.1413 ve 0.0439 mg/mL IC50 değerleri hesaplanmıştır. Bir antosiyanin bileşiği olarak malvidin-3-O-glukozit HPLC yardımıyla tespit edilmiştir. Sitotoksite analizi, farklı konsantrasyonlar (0.5-10 mg/ml) arasında 2 mg/ml V. myrtillus meyve metanol ekstresinin, sağlıklı MSC hücrelerini korurken AGS mide kanseri hücrelerinin canlılığını azalttığını göstermiştir. Bu veriler, Yaban mersini özünün çeşitli kanser hücre dizileri üzerinde daha fazla analiz edilmesini ve ekstresindeki potansiyel aktif maddelerin belirlenmesini önermektedir

Wound physiology and experimental wound models: Traditional review

Yara, vücuda gelebilecek bir yaralanma sonucu cildin epidermisinde hasar oluşması ve derinin normal anatomisinin ve fonksiyonlarının bozulması olarak tanımlanır. Yara iyileşmesi, kazayla veya kasıtlı olarak meydana gelen travma sonrası derinin bütünlüğünü korumak için önemli bir fizyolojik süreçtir. Normal yara iyileşmesi, hemostaz/inflamatuar faz, inflamasyon, proliferatif faz ve yeniden şekillenme fazı dâhil olmak üzere birbirini takip eden ve üst üste binen 4 fazı içerir. Yara iyileşmesi; yaş, eşlik eden hastalık, beslenme ve hijyen gibi birçok faktör tarafından etkilenmektedir. Aşırı yara iyileşmesi (hipertrofik skar ve keloid) veya kronik yara (ülser), bozulmuş fizyolojik yara iyileşme süreçlerinin göstergesidir. Yaraların temelde akut/kronik olarak ayrılmasının yanında, oluştuğu bölge (ağız, göz, deri vb.) ve oluşumuna göre (travmaya bağlı yara, diyabetik yara ve yanık yaraları) sınıflandırılması, bakımı ve tedavisi açısından farklılıklar oluşturmaktadır. Genel olarak topikal antiseptikler ile yapılan geleneksel yara bakımının yanında günümüzde otogreftler, allogreftler, kültürlü epitelyal otogreftler ve biyouyumlu ve biyobozunur polimerlere dayalı yara pansumanları gibi tedavi seçenekleri de bulunmaktadır. Deneysel yara modelleri, terapötik potansiyele sahip yeni ajanları test etmek, doku onarım mekanizmasının patogenezini incelemek ve yeni biyobelirteçleri saptamak için gereklidir. İn silico, in vitro ve in vivo dâhil olmak üzere yara iyileşme sürecini incelemek için çeşitli modeller kullanılmıştır. Bunun yanında, hiçbir deneysel yara modeli fizyolojik yara iyileşmesini tam olarak temsil etmediği için farklı modelleri içeren uygun bir kombinasyon kullanılmalıdır. Bu derlemede; yara tipleri, yara iyileşmesi, in vitro ve in vivo deneysel yara modelleri tartışılmaktadır.Wound is defined as damage to the epidermis of the skin and disruption of the normal anatomy and functions of the skin as a result of an injury to the body. Wound healing is an important physiological process to preserve the integrity of the skin after accidental or intentional trauma. Normal wound healing includes four consecutive and overlapping phases, including the hemostasis/inflammatory phase, the inflammation, the proliferative phase, and the remodeling phase. Wound healing; it is affected by many factors such as age, concomitant disease, nutrition and hygiene. Excessive wound healing (hypertrophic scar and keloid) or chronic wound (ulcer) is indicative of impaired physiological wound healing processes. In addition to the acute/chronic division of wounds, the classification according to the region (mouth, eye, skin etc.) and formation (traumatic wound, diabetic wound and burn wounds) creates differences in terms of care and treatment. In addition to traditional wound care with topical antiseptics in general, treatment options such as autografts, allografts, cultured epithelial autografts and wound dressings based on biocompatible and biodegradable polymers are now available. Experimental wound models are required to test new agents with therapeutic potential, to study the pathogenesis of tissue repair mechanism, and to detect new biomarkers. Various models have been used to study the wound healing process, including in silico, in vitro, and in vivo. In addition, an appropriate combination of different models should be used, as no experimental wound model is fully representative of physiological wound healing. In this review, wound types, wound healing, in vitro and in vivo experimental wound models are discussed

Phlomis Pungens’in fitokimya ve in vitro farmakolojik etkilerinin değerlendirilmesi

Objective: This study aimed to investigate the in vitro wound healing, anti-inflammatory, antimicrobial and antioxidant activity of Phlomis pungens Willd. extract derived from the aerial parts. Material and Method: The phytochemical analysis was performed using GC-MS in order to identify the volatile components of the bioactive Hex extract. The wound healing activity of P. pungens extract was evaluated based on in vitro antimicrobial, antioxidant, anti-inflammatory, and, scratch activity was studied. In addition, the in vitro cytotoxicity of the extract was also evaluated. Result and Discussion: P. pungens methanol extract depicted a 5-LOX inhibitory activity at 78.2µg/mL (IC50), while the antioxidant activity by DPPH radical provided an IC50=2.41mg/mL, and the ABTS radical showed IC50=3.32mg/mL, respectively. The extract showed dose-dependently anti-inflammatory activity while L-NAME and P. pungens methanol extract significantly decreased LPS stimulated PGE2 production. According to the scratch assay results, all treatments led to an increase in cell migration rate with a dose-dependent effect. Our findings suggested that P. pungens methanol extract may have a role in wound healing according to the scratch test, and it is thought that its antioxidant and anti-inflammatory activity also contributed. Further evaluations are ongoing to confirm the in vitro activity under in vivo conditions.Amaç: Bu çalışmada, Phlomis pungens Willd. topraküstü kısımlarından elde edilen ekstrelerin in vitro yara iyileşmesi, antiinflamatuar, antimikrobiyal ve antioksidan aktivitesinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Biyoaktif hekzan ekstresinin uçucu bileşenlerini belirlemek için fitokimyasal analiz GC-MS kullanılarak yapılmıştır. P. pungens ekstresinin yara iyileştirme aktivitesi, in vitro antimikrobiyal, antioksidan, antiinflamatuar etkinlikleri değerlendirilmiş ve ek olarak ekstrenin in vitro sitotoksisitesi de değerlendirilmiştir. Sonuç ve Tartışma: P. pungens metanol ekstresi, 78,2 µg/mL'de (IC50) 5-LOX inhibe edici aktivite gösterirken, DPPH yöntemi ile antioksidan aktivitesi IC50=2.41mg/mL ve ABTS IC50=3.32 mg/mL olarak bulunmuştur. Ekstre, doza bağlı olarak anti-inflamatuar aktivite gösterirken, L-NAME ve P. pungens metanol ekstresi, LPS ile uyarılan PGE2 üretimini önemli ölçüde azaltmıştır. Strach metodu sonuçlarına göre doza bağlı etki ile hücre göç hızında bir artış gözlemlenmiştir. Bulgularımız, starch testine göre P. pungens metanol ekstresinin yara iyileşmesinde rol oynayabileceğini ve antioksidan ve antiinflamatuar aktivitesinin de katkıda bulunduğu düşündürmüştür. İn vivo koşullar altında in vitro aktiviteyi doğrulamak için başka değerlendirmeler devam etmektedir