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

Comparison of intestinal permeability of nebivolol hydrochloride loaded solid lipid nanoparticles with commercial nebivolol tablet

WOS: 000458080300013The oral application of drugs is the most popular route for achieving systemic effects, nevertheless, it is limited by difficulties related to physicochemical properties of the drug. Solid lipid nanoparticles (SLNs) are appealing extensive notice because of showing increased solubility and improved oral bioavailability via different mechanisms. The aim of the study is to compare and peruse the in-situ permeation of nebivolol (NBV) loaded SLN and its commercial tablet formulation used for the treatment of hypertension. For this aim Single-Pass Intestinal Perfusion (SPIP) method was used for in-situ permeation studies. NBV loaded SLNs were prepared and modified with polyethylene glycol (PEG). In order to prepare SLNs by homogenization technique, compritol, lecithin and poloxamer were chosen. Particle sizes of blank and loaded SLN were 213.4 +/- 17.5 and 264.1 +/- 18.8 nm, respectively with polydispersity index values of approximately 0.3 for each. NBV loading resulted in positive electrical charge on SLNs. The encapsulation efficiency was 98.04 +/- 0.2 %. Permeability coefficient values were tripled when NBV was incorporated in SLNs and doubled when pure NBV was given separately with a blank SLN. PEG modified SLN can be used to enhance oral absorption of NBV, and SLNs alone can be used as permeation enhancer in oral drug delivery..TUBITAK [112S292]This study was supported by TUBITAK Project No: 112S292. The authors would like to thank Novartis (Novartis Drug Co., Turkey) for providing metoprolol tartrate. The authors would also like to thank to Ege University, Faculty of Pharmacy, Pharmaceutical Sciences Research Center (FABAL) for high pressure homogenization facilities

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

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

Antibiyotik içeren çeşitli oküler nano-taşıyıcı sistemlerin in vitro-in vivo değerlendirilmesi üzerine çalışmalar

Bakteriyal keratit, çok sık karşılaşılan bir kornea hastalığıdır. Özellikle dirençli bakteriler ile tekrarlayan durumlarda, tedavi edilmediği takdirde genellikle körlüğe yol açmaktadır. Ofloksasin bakteriyal keratit tedavisinde uzun zamandan beri kullanılan florokinolon türü bir antibiyotiktir. Ofloksasin’in oftalmik kullanıma özel çözelti şeklinde farmasötik formları mevcuttur. Ne yazık ki günümüze kadar bakteriyal keratit tedavisinde antibakteriyal amaçla uygulanan ilaçlar göz yüzeyinde çok kısa süre kalarak gözyaşı ile enflamasyon bölgesinden akarak uzaklaşmaktadır. Oküler uygulanan ilaçlarda karşılaşılan en temel sorun, kornea bariyerinin geçilememesi ve göz yüzeyinde kalış süresinin çok az olmasıdır. Bu nedenlerle göz yüzeyinde oluşan enfeksiyonların tedavisinde istenen düzeyde başarı elde edilememektedir. Bu çalışmada tüm bu sorunların üstesinden gelmek amacıyla mikroemülsiyon formülasyonu ve yüksek devirli homojenizasyon ve mikroemülsiyon yöntemi ile nano yapılı lipit taşıyıcı formülasyonları hazırlanmıştır. Bu formülasyonlarda yağ olarak oleik asit, katı lipit olarak CHD 5, YEM olarak Tw 80 kullanılmıştır. OFX % 0.3 oranında ilave edilmiştir. Formülasyonların zeta potansiyellerinin arttırılması amacıyla formülasyonlara suda çözünen bir polimer olan kitozan oligosakkarit laktat ilave edilmiştir. Tüm kolloidal formülasyonlar pH, elektriksel iletkenlik, viskozite, TEM görüntüleri, yükleme etkinliği, içerik miktarı, partikül büyüklüğü, zeta potansiyeli ve salım profilleri açısından değerlendirilmiştir. Göz yüzeyinde kalma açısından önemli bir parametre olan zeta potansiyel değeri en yüksek olan formülasyon NH34 bulunmuştur. Tüm karakterizasyon sonuçları açısından formülasyonların tamamının göze uygulanılabilecek özellikte olduğu tespit edilmiştir. Kararlılık çalışmaları sonucunda 4 oC ve 25 oC’de tüm kolloidal formülasyonların vizkozite, partikül büyüklüğü, zeta potansiyeli, pH değeri, OFX miktarı ve fiziksel görünüş açısından 12 ay boyunca kararlı oldukları görülmüştür. Yüksek devirli homojenizatör yöntemi ile elde edilen NH34 formülasyonundan hareketle insert formülasyonu çözücü uçurma yöntemi ile elde edilmiştir. İnsert formülasyonlarının geliştirilmesinde bazı formülasyonlara kitozan yerine polimer olarak yine suda çözünen % 0.75 oranında aljinat kullanılmıştır. İnsert formülasyonlarının kalınlık, çap, ağırlık, kırılabilirlik, etkin madde miktarı tespiti, nem absorplama, nem miktarı, yüzey görüntüleri, DSC analizi ve biyoadezyon gibi özellikleri araştırılmıştır. Salım özellikleri incelendiğinde polimer olarak aljinat içeren insertler 8 saatte %100 salımını tamamlamıştır, kitozan içeren insertler ise 36 saatte salımı % 95 civarında yaptığı görülmüştür. Biyoadezyon özellikleri incelendiğinde F3 formülasyonun en yüksek eğri altı alanına sahip olduğu görülmüştür. F3 insertinin özelliklerinin 1 ay boyunca saklanılan ortamlarda kararlı olduğu tespit edilmiştir. Difüzyon hücreleri kullanarak yapılan difüzyon çalışmalarında diyaliz memran kullanıldığında reseptör faza geçiş olduğu tespit edilmiştir. Membran yerine kornea dokusu kullanıldığında ise % 0.7 - 3.5 aralığında çok az bir difüzyon görülmüştür. Kitozan içeren insertlerde herhangi bir difüzyona rastlanmamıştır. Mikrobiyolojik çalışmalar kapsamında, elde edilen formülasyonların sterilizasyonu kontrol edilmiş ve göze uygulanma açısından steril oldukları tespit edilmiştir. OFX’in minunum etkin konsantrasyonu S. aureus ve E. coli’ye karşı araştırılmış ve sırasıyla 0,78 ve 0,39 µg/mL olarak tespit edilmiştir. Formülasyonların in vitro antibakteriyal etkinliklerini araştırmak amacıyla disk difüzyon testi yapılmıştır. Formülasyonlar karşılaştırıldığında kitozanın artibakteriyel aktiviteye katkısı olduğu anlaşılmış ve kitozan içeren formülasyonların içermeyenlere göre etkinliğinin daha fazla olduğu görülmüştür. Bununla birlikte insert formülasyonlarında ise aljinatın E. coli’ye etkili olduğu, S. aureus’a karşı etkisiz olduğu görülmüştür. Formülasyonların göz yüzeyinde kalma süreleri tavşanlarda kıyaslanarak yapılmıştır. NH34 formülasyonu göz yüzeyinde 1 saat kalarak, göz yüzeyinde en uzun süre kalmayı başarabilmiştir. Çözelti tipinde olan ticari preparat ise 10 dakikada göz yüzeyinden kaybolmuştur. Aljnat içeren insertler 3 saat kalmayı başarabilmiş, kitozan içeren insertler ise 24 saat süre boyunca alt göz kapağında kalabildiği tespit edilmiştir. Keratit oluşturulmuş tavşanlar 1 hafta boyunca tedavi edilmiş ve formülasyonların etkinlikleri kıyaslamıştır. Tüm formülasyonların tedavide etkili olduğu gözlenmiştir. Aköz hümörden miktar tayini yapılmış ve aköz hümöre geçen konsantrasyonların minumum etkin konsatrasyondan daha yüksek olduğu tespit edilmiştir. Sonuç olarak, OFX’in daha etkin bir keratit tedavisi sağlaması amacıyla topikal mikroemülsiyon, nanoyapılı lipid taşıyıcılar ve insert formulasyonları başarı ile hazırlanmış ve istenilen oftalmik özelliklerin sağlandığı görülmüştür. Uzun süre gözde kalabilen insert formülasyonları ile hasta uyuncunun artması sağlanabilir ve uygulama sıklığı azaltılabilir

Development and validation of an HPLC method for voriconazole active substance in bulk and its pharmaceutical formulation

WOS: 000379969900004The aim of the present study was to develop and validate a High-Performance Liquid Chromatography (HPLC) method for the determination of voriconazole in drug substances and in situ gel. A mixture of acetonitrile and ultrapure water (50: 50) (v/v) was used as mobile phase. The column was a C18 column (150x4.6mm with 5 mu m particles). The eluent was monitored with UV detection at 256 nm and flow rate was set to 1 mL/min. The method was validated partially with respect to system suitability, linearity, limits of detection (LOD) and quantitation (LOQ), precision, accuracy, specificity, selectivity and stability. Obtained results showed that the analytical method had good linearity, accuracy, precision, selectivity and stability. Analytical method development results indicated that the LOD was 0.022 mu g/mL; LOQ was 0.065 mu g/mL and assay exhibited a linear range of 1-30 mu g/mL

Hypertension in 2017: Update in treatment and pharmaceutical innovations

WOS: 000425370400010PubMed ID: 28969533Hypertension can be referred to as modern scourge in 2017 and although, it seems that an improvement has been done during the passage of time, the full treatment still remains an unmet achievement for clinicians. Hypertension incidence in Mediterranean countries, especially Greece and Turkey, seems to be increasing irrespective of the expected protective effect of Mediterranean diet. The changed lifestyle and dietary habits of both populations led to advanced cardiovascular events and arteriosclerosis both of which are linked with high blood pressure. From statistic aspect, as in this work reviewed, it has been found out that gender, age, sociodemographic characteristics and geographical location could promote the hypertension prevalence. Given the above, as well as the fact that the current pharmaceutical formulations do not present the optimal results on hypertension management, summing up the ongoing research on hypertension field is in high demand. Consequently, the development of novel solutions for high blood pressure management either with new synthesized drugs or fascinated drug delivery systems is required. Moreover, adopting healthy lifestyle and diet also plays a crucial role against hypertension. This review is aimed at assisting researchers working on hypertension management by summarizing update guidelines, various case reports describing hypertension related with other diseases, current medications and newly synthesized drug delivery systems recently found in literature

Surface modified multifunctional and stimuli responsive nanoparticles for drug targeting: Current status and uses

WOS: 000385525500067PubMed ID: 27589733Nanocarriers, due to their unique features, are of increased interest among researchers working with pharmaceutical formulations. Polymeric nanoparticles and nanocapsules, involving non-toxic biodegradable polymers, liposomes, solid lipid nanoparticles, and inorganic-organic nanomaterials, are among the most used carriers for drugs for a broad spectrum of targeted diseases. In fact, oral, injectable, transdermal-dermal and ocular formulations mainly consist of the aforementioned nanomaterials demonstrating promising characteristics such as long circulation, specific targeting, high drug loading capacity, enhanced intracellular penetration, and so on. Over the last decade, huge advances in the development of novel, safer and less toxic nanocarriers with amended properties have been made. In addition, multifunctional nanocarriers combining chemical substances, vitamins and peptides via coupling chemistry, inorganic particles coated by biocompatible materials seem to play a key role considering that functionalization can enhance characteristics such as biocompatibility, targetability, environmental friendliness, and intracellular penetration while also have limited side effects. This review aims to summarize the state of the art of drug delivery carriers in nanosize, paying attention to their surface functionalization with ligands and other small or polymeric compounds so as to upgrade active and passive targeting, different release patterns as well as cell targeting and stimuli responsibility. Lastly, future aspects and potential uses of nanoparticulated drug systems are outlined

Preparation and evaluation of QbD based fusidic acid loaded in situ gel formulations for burn wound treatment

The purpose of this research was to prepare and evaluate the potential use of in situ gel formulations for dermal delivery of fusidic acid for burn wound treatment. Temperature sensitive in situ gels were successfully developed by the cold technique using poloxamer 188, poloxamer 407, poloxamer 338. Finally, the concentration of fusidic acid in formulations was 2% (w/w). The developed formulations were optimized using quality by design (QbD) approach. The prepared formulations were evaluated for clarity, sol-gel transition temperature, gelling capacity, pH, viscosity and drug content. The gelation temperatures of all the fusidic acid loaded formulations were within the range of 30–34 °C. Furthermore, sterility, antibacterial activity, stability, in vitro fusidic acid release, ex vivo permeation, and penetration study of these formulations were also examined. The wound healing feature was appraised by determining the wound contraction and by a histopathological survey. Based on the observed antimicrobial and wound healing effects, the formulations containing fusidic acid could be employed as an alternative to commercial cream. This novel formulation can be employed for making burn wound healing process more efficient