Development and validation of highly selective method for the determination of imatinib mesylate and dexketoprofen trometamol combination in three different media

Imatinib mesylate is a small molecule used in cancer therapy as a thyrosine kinase inhibitor. Dexketoprofen trometamol is a non-steroidal anti-inflammatory drug that has seen use in cancer therapy in combination with an anticancer drug to minimize tumor size and to reduce pain in patients. In the present study, imatinib mesylate and dexketoprofen trometamol were selected as potential model drugs to be used in combination. A new, simple and selective Ultra Performance Liquid Chromatography method was developed and validated to determine the drug substances in distilled water, in a pH 7.4 phosphate buffer and in Dulbecco’s Modified Eagle Medium. The proposed method was developed using a BEH C-18 column with isocratic elution. A mixture of methanol:acetonitrile (80:20, v/v) and pH 9.5, 0.05 M ammonium acetate were (70:30, v/v) used as a mobile phase. Detection was carried out with a flow rate of 0.3 mL/min, a column temperature of 30°C and an injection volume of 20 µL. The method was validated considering linearity, accuracy, precision, specificity, robustness, detection limit and quantitation limit values, and was found to be linear in a range from 0.05 to 20.0 µg/mL for the three different media

Opportunities for topical antimicrobial therapy: permeation of canine skin by fusidic acid

BACKGROUND: Staphylococcal infection of the canine epidermis and hair follicle is amongst the commonest reasons for antimicrobial prescribing in small animal veterinary practice. Topical therapy with fusidic acid (FA) is an attractive alternative to systemic therapy based on low minimum inhibitory concentrations (MICs, commonly <0.03 mg/l) documented in canine pathogenic staphylococci, including strains of MRSA and MRSP (methicillin-resistant Staphylococcus aureus and S. pseudintermedius). However, permeation of canine skin by FA has not been evaluated in detail. This study aimed to define the degree and extent of FA permeation in canine skin in vitro from two sites with different hair follicle density following application of a licensed ophthalmic formulation that shares the same vehicle as an FA-betamethasone combination product approved for dermal application in dogs. Topical FA application was modelled using skin held in Franz-type diffusion cells. Concentrations of FA in surface swabs, receptor fluid, and transverse skin sections of defined anatomical depth were determined using high-performance liquid chromatography and ultraviolet (HPLC-UV) analysis. RESULTS: The majority of FA was recovered by surface swabs after 24 h, as expected (mean ± SEM: 76.0 ± 17.0%). FA was detected within 424/470 (90%) groups of serial sections of transversely cryotomed skin containing follicular infundibula, but never in 48/48 (100%) groups of sections containing only deeper follicular structures, nor in receptor fluid, suggesting that FA does not permeate beyond the infundibulum. The FA concentration (mean ± SEM) in the most superficial 240 μm of skin was 2000 ± 815 μg/g. CONCLUSIONS: Topically applied FA can greatly exceed MICs for canine pathogenic staphylococci at the most common sites of infection. Topical FA therapy should now be evaluated using available formulations in vivo as an alternative to systemic therapy for canine superficial bacterial folliculitis.Peer reviewedFinal Published versio

The design of naproxen solid lipid nanoparticles to target skin layers

The aim of the current investigation was to produce naproxen solid lipid nanoparticles (Nap-SLNs) by the ultrasonication method to improve its skin permeation and also to investigate the influence of Hydrophilic-lipophilic balance (HLB) changes on nanoparticles properties. The properties of obtained SLNs loaded with naproxen were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). FT-IR was also used to investigate any interaction between naproxen and the excipients used at the molecular level during the preparation of the SLNs. The performance of the formulations was investigated in terms of skin permeation and also the retention of the drug by the skin. It was found that generally, with increasing the lipid concentration, the average particle size and polydispersity index (PDI) of SLNs increased from 94.257 ± 4.852 nm to 143.90 ± 2.685 nm and from 0.293 ± 0.037 to 0.525 ± 0.038 respectively. The results also showed that a reduction in the HLB resulted in an increase in the PDI, particle size, zeta potential and entrapment efficiency (EE %). DSC showed that the naproxen encapsulated in the SLNs was in its amorphous form. The peaks of prominent functional groups of naproxen were found in the FT-IR spectra of naproxen-SLN, which confirmed the entrapment of naproxen in the lipid matrix. FT-IR results also ruled out any chemical interaction between drug and the chemicals used in the preparation of SLNs. The amount of naproxen detected in the receptor chamber at all the sampling times for the reference formulation (naproxen solution containing all surfactants at pH 7.4) was higher than that of the Nap-SLN8 formulation. Nap-SLN8 showed an increase in the concentration of naproxen in the skin layer with less systemic absorption. This indicates that most of the drug in Nap-SLN8 remains in the skin which can reduce the side effect of systemic absorption of the drug and increases the concentration of the drug at the site of the action

Microneedles: A New Frontier in Nanomedicine Delivery

This review aims to concisely chart the development of two individual research fields, namely nanomedicines, with specific emphasis on nanoparticles (NP) and microparticles (MP), and microneedle (MN) technologies, which have, in the recent past, been exploited in combinatorial approaches for the efficient delivery of a variety of medicinal agents across the skin. This is an emerging and exciting area of pharmaceutical sciences research within the remit of transdermal drug delivery and as such will undoubtedly continue to grow with the emergence of new formulation and fabrication methodologies for particles and MN. Firstly, the fundamental aspects of skin architecture and structure are outlined, with particular reference to their influence on NP and MP penetration. Following on from this, a variety of different particles are described, as are the diverse range of MN modalities currently under development. The review concludes by highlighting some of the novel delivery systems which have been described in the literature exploiting these two approaches and directs the reader towards emerging uses for nanomedicines in combination with MN

TURKISH FANTASY FICTION FILMS THEN AND NOW: AN ANALYSIS OF FANTASY FILMS PRODUCED IN EARLY 1970s TURKEY

Turkish cinema has produced very few examples of fantasy fiction genre films since its beginning in 1914 except for the 1970s Yeşilçam era. The first film ever to be made in Turkey by a Turkish filmmaker (Fuat Uzkınay) is credited as Ayastefanos’taki Rus Abidesinin Yıkılışı (The Destruction of the Russian Monument at Ayastefanos) (Panaite, 8), which is an actuality film similar to Lumiere brothers’ shorts. The lack of recognition of fantasy fiction in Turkish film history and literature can be attributed to the social and political movements along with the modernization process in the republic’s history to migration, alienation, and the contradictory Turkish identity. A survey of Turkish novels reveals a parallel lack of fantasy fiction in literature. In analyzing this lack of fantasy fiction films in literature, Veli Uğur concludes that it is the late modernization process (he claims starts with early 2000’s) within the Turkish social, cultural sphere that influenced this almost complete non-existence of the genre (136). A late modernization is not sufficient to explain the fantasy fictions rise in 1970s and complete disappearance afterwards in Turkish cinema. This project’s main concern is to identify the reasons behind the lack of fantasy fiction films in Turkish cinema by analyzing the films produced in the early peak period of Yeşilçam (early 1970s). I look at the cinematic texts through the lens of attachment to realism and tradition, the refusal and re-appearance of folklore, the definition of Turkish identity prior to the acceptance of Islam, and the severed ties with the Ottoman identity. These factors all created a crisis for the modern Turk. The investigation addresses the effect of the emerging Turkish culture of the early 1970s on the production and perception of fantasy in films as a way of unearthing the social struggles and desires of that time. Contrary to mainstream literature, the Yeşilçam (Green Pine) era (roughly between 1960 and 1980) produced quite a few examples (36 in total from 1970 to 1979 (Önk, 3875)); however, these are only A movies and thus the perception that there aren’t many fantasy films produced in Turkey is wrong. If B films with low-budgets are added the total number rises to 135 films out of a total of roughly 200 films were produced during this nine-year period. The influence of European and American culture after the proclamation of Turkey as a republic in 1923 aided a rise in art and cultural events (such as film festivals) that affected the production of films. Yeşilçam was the peak of this movement towards modernization, and although the production values and budgets for the films were very low, became they extremely successful. These films were produced and distributed for the Turkish audience. Turkish movie theaters of the 1970’s were mainly in big cities

The application of feature selection to the development of Gaussian process models for percutaneous absorption.

The definitive version can be found at: http://www3.interscience.wiley.com/ Copyright Royal Pharmaceutical Society of Great BritainObjectives: The aim was to employ Gaussian processes to assess mathematically the nature of a skin permeability dataset and to employ these methods, particularly feature selection, to determine the key physicochemical descriptors which exert the most significant influence on percutaneous absorption, and to compare such models with established existing models. Methods: Gaussian processes, including automatic relevance detection (GPRARD) methods, were employed to develop models of percutaneous absorption that identified key physicochemical descriptors of percutaneous absorption. Using MatLab software, the statistical performance of these models was compared with single linear networks (SLN) and quantitative structure–permeability relationships (QSPRs). Feature selection methods were used to examine in more detail the physicochemical parameters used in this study. A range of statistical measures to determine model quality were used. Key findings: The inherently nonlinear nature of the skin data set was confirmed. The Gaussian process regression (GPR) methods yielded predictive models that offered statistically significant improvements over SLN and QSPR models with regard to predictivity (where the rank order was: GPR > SLN > QSPR). Feature selection analysis determined that the best GPR models were those that contained log P, melting point and the number of hydrogen bond donor groups as significant descriptors. Further statistical analysis also found that great synergy existed between certain parameters. It suggested that a number of the descriptors employed were effectively interchangeable, thus questioning the use of models where discrete variables are output, usually in the form of an equation. Conclusions: The use of a nonlinear GPR method produced models with significantly improved predictivity, compared with SLN or QSPR models. Feature selection methods were able to provide important mechanistic information. However, it was also shown that significant synergy existed between certain parameters, and as such it was possible to interchange certain descriptors (i.e. molecular weight and melting point) without incurring a loss of model quality. Such synergy suggested that a model constructed from discrete terms in an equation may not be the most appropriate way of representing mechanistic understandings of skin absorption.Peer reviewedFinal Accepted Versio

Nanoparticle and liposome formulations of doxycycline: Transport properties through Caco-2 cell line and effects on matrix metalloproteinase secretion

Nanoparticle and liposome formulations containing doxycycline or doxycycline and sodium taurocholate (NaTC) were developed in this study. The anticancer effects of doxycycline and penetration properties from those formulations through Caco-2 cell monolayers were investigated. Matrix metalloproteinases (MMPs) have been reported to play a role in the negative prognosis of many malignant tumors including glioblastoma multiforme (GBM). This study is presented to demonstrate that these developed nanoparticle and liposome formulations of doxycycline are capable of inhibiting MMP-2 release from cultured Caco-2 cells. In this study, Caco-2 cells were used as model cell cultures. A MTT test was performed to determine the effect of doxycycline on the viability of Caco-2 cells. Doxycycline nanoparticles were prepared using emulsion polymerization and doxycycline liposomes were prepared using the dry film hydration method. Transport studies of doxycycline through Caco-2 cells were investigated. MMP-2 was found to be inhibited more with doxycycline if NaTC is present in the formulation. NaTC was also found to be useful to increase penetration due to the inhibition of efflux by interacting with p-glycoproteins, in addition to the penetration enhancing effect as a result of opening tight junctions. These developed formulations were proposed to use for the treatment of tumors and GBM. (C) 2013 Elsevier Masson SAS. All rights reserved.Nanoparticle and liposome formulations containing doxycycline or doxycycline and sodium taurocholate (NaTC) were developed in this study. The anticancer effects of doxycycline and penetration properties from those formulations through Caco-2 cell monolayers were investigated. Matrix metalloproteinases (MMPs) have been reported to play a role in the negative prognosis of many malignant tumors including glioblastoma multiforme (GBM). This study is presented to demonstrate that these developed nanoparticle and liposome formulations of doxycycline are capable of inhibiting MMP-2 release from cultured Caco-2 cells. In this study, Caco-2 cells were used as model cell cultures. A MTT test was performed to determine the effect of doxycycline on the viability of Caco-2 cells. Doxycycline nanoparticles were prepared using emulsion polymerization and doxycycline liposomes were prepared using the dry film hydration method. Transport studies of doxycycline through Caco-2 cells were investigated. MMP-2 was found to be inhibited more with doxycycline if NaTC is present in the formulation. NaTC was also found to be useful to increase penetration due to the inhibition of efflux by interacting with p-glycoproteins, in addition to the penetration enhancing effect as a result of opening tight junctions. These developed formulations were proposed to use for the treatment of tumors and GBM. (C) 2013 Elsevier Masson SAS. All rights reserved.</p