Encapsulation of water insoluble drugs in mesoporous silica nanoparticles using supercritical carbon dioxide

Mesoporous silica nanoparticles MCM – 41 were synthesized with two dimensional hexagonal p6mm symmetry, high specific surface area(~ 980m2/g) narrow pore size and an average particle size of 186 nm. The produced nanoparticles were used to encapsulate carbamazepine through a supercritical carbon dioxide process combined with various organic solvents. Supercritical processing was found to provide increased drug encapsulation. The loaded MCM - 41 nanoparticles were analyzed using X–ray diffraction and differential scanning calorimetry (DSC) to investigate the crystalline state of the encapsulated carbamazepine and it was found to be dependent on the nature of the organic solvent. Carbamazepine showed increased dissolution rates under sink conditions. Viability studies of Caco – 2 cells demonstrated negligible cytotoxicity for the MCM–41 nanoparticles

Between Central State and Local Society

This thesis aspires to contribute to the study of change instigated by social engineering projects that were devised and executed by state elites upon targeted populations. Focusing on the Turkish case of social engineering in the 1930s and 1940s, this thesis studies such a moment of change from a perspective that is alternative to and critical of the ‘modernization’ and ‘dependency’ paradigms. It focuses on the People’s House, an institution the Turkish state established in the 1930 and 40 with the direct aim to introduce the reforms to the population. More specifically, it is a case study of two provincial People’s Houses, their clientele and their activities. Finally, it focuses on three policies of the People’s Houses, i.e. women and villager related activities, and new forms of socialization in contrast to the old coffeehouse type of socialization. This study treats the resistance and accommodation to these p olicies by local social actors as productive for the shaping of new social identities, collective and personal, but also as indicative of the limits of a state that is otherwise considered the sole instigator of social change in the literature of the Turkish Republic.Middle Eastern Studie

Engineering and manufacturing of pharmaceutical co-crystals : a review on solvent-free manufacturing technologies

Design and synthesis of pharmaceutical cocrystals have received great interest in the recent years. Cocrystallization of drug substances offer a tremendous opportunity for the development of new drug products with superior physical and pharmacological properties such as solubility, stability, hydroscopicity, dissolution rates and bioavailability. It is now possible to engineer and develop cocrystals via ‘green chemistry' and environmental friendly approaches such as solid-state synthesis in the absence of organic solvents. In addition, significant efforts are placed on computational screening, cocrystal manufacturing in a continuous manner and real-time monitoring for quality purposes by using various analytical tools. Pharmaceutical cocrystals are not fully exploited yet and there is a lot of ground to cover before they can be successfully utilized as medical products

Stimuli Responsive Polymeric Systems for Cancer Therapy.

Nanoscale polymers systems have dominated the revolution of drug delivery advancement. Their potential in the fight against cancer is unrivalled with other technologies. Their functionality increase, targeting ability and stimuli responsive nature have led to a major boom in research focus. This review article concentrates on the use of these smart polymers in cancer therapy. Nanotechnologies have shown potential as drug carriers leading to increased drug efficacy and penetration. Multifunctional smart carriers which can release their payload upon an external or internal trigger such as pH or temperature are proving to be major frontrunners in the development of effective strategies to overcome this disease with minimal patient side effects

An investigation into fused filament fabrication for pharmaceutical manufacturing

In a modern world, what is the best way to deliver medicines to the patient? Human beings are an extremely diverse species with many different factors that can influence the behaviour of a drug within the body. Children are a perfect example of such variety. Doses are often prescribed based on body weight, and can vary greatly from infants to adolescents. With current ‘traditional’ manufacture of oral dose pharmaceuticals, generally only a limited number of doses are produced, leading to difficulties with appropriate dosing. The ability to manufacture personalised doses for these patients would be of great benefit both practically and financially, and may even lead to ‘point of care’ manufacture

Bioinspired Silica Offers a Novel, Green, and Biocompatible Alternative to Traditional Drug Delivery Systems

Development of drug delivery systems (DDS) is essential in many cases to remedy the limitations of free drug molecules. Silica has been of great interest as a DDS due to being more robust and versatile than other types of DDS (e.g., liposomes). Using ibuprofen as a model drug, we investigated bioinspired silica (BIS) as a new DDS and compared it to mesoporous silica (MS); the latter has received much attention for drug delivery applications. BIS is synthesized under benign conditions without the use of hazardous chemicals, which enables controllable in situ loading of drugs by carefully designing the DDS formulation conditions. Here, we systematically studied these conditions (e.g., chemistry, concentration, and pH) to understand BIS as a DDS and further achieve high loading and release of ibuprofen. Drug loading into BIS could be enhanced (up to 70%) by increasing the concentration of the bioinspired additive. Increasing the silicate concentration increased the release to 50%. Finally, acidic synthesis conditions could raise loading efficiency to 62% while also increasing the total mass of drug released. By identifying ideal formulation conditions for BIS, we produced a DDS that was able to release fivefold more drug per weight of silica when compared with MCM-41. Biocompatibility of BIS was also investigated, and it was found that, although ∼20% of BIS was able to pass through the gut wall into the bloodstream, it was nonhemolytic (∼2% hemolysis at 500 μg mL–1) when compared to MS (10% hemolysis at the same concentration). Overall, for DDS, it is clear that BIS has several advantages over MS (ease of synthesis, controllability, and lack of hazardous chemicals) as well as being less toxic, making BIS a real potentially viable green alternative to DDS

Incidence of Insomnia in OSA patients and its correlations with parameters of polysomnography

Background/Aims: Prevalence of insomnia in obstructive sleep apnoea (OSA) patients has been estimated in many studies and has been found to be a frequent symptom (38% in a recent review 1).Our study aims to estimate the incidence of insomnia in Greek patients presenting to a public hospital sleep clinic, and correlate it with the severity of OSA and parameters of polysomnography (PSG). Methods: 100 patients who visited the sleep unit of the General Hospital ‘Evangelismos’ completed the Athens Insomnia Scale (AIS) and underwent a polysomnographic study. 56% were men, with mean age 54,7±12,5 years and BMI 31,5±6,2. Results: 70% of patients had insomnia. Insomnia (AIS≥6) and OSA (AHI≥5) were coexistent in 71,4 %. There was no correlation between insomnia and severity of OSA. A strong positive correlation was found/evident between difficulty in initiating sleep and number of hypopneas (r: 0,20 p:0,049), diminished functioning during the day and leg movements (r:0,21 p:0,050) and between daytime sleepiness and wake after sleep onset (WASO) (r:0,2 p:0,038). A negative correlation was found between overnight awakenings and sleep efficiency (r: -0,23 p: 0,021). Also, negative correlation was found between early morning awakening and minimum SpO2 (r=0.27, p=0,021), and between insufficient duration of sleep (r:-0,22 p: 0,021) and minimum SpO2. Conclusions: We found a high incidence of insomnia in patients with OSA, which does not correlate with severity of OSA. Contrary to many other studies, insomnia was not more common in women. More studies are required to clarify the significance of the positive correlation between insomnia and number of hypopneas and minimum SpO2

Microfluidic encapsulation method to produce stable liposomes containing iohexol

Since the discovery of X-rays in the late 1890s, several medical imaging techniques have been developed, such as Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and Ultrasound Imaging, which are used daily to diagnose, monitor, or treat medical conditions. Some of these techniques include the use of contrast agents to enhance the contrast images, therefore, toxic effects must be considered. Among these, Contrast-Induced Nephropathy (CIN) is an acute renal failure resulting from the administration of iodinated contrast media (CM). To date, there is no definitive treatment for CIN and several prevention approaches have been evaluated. Nanoparticles (NPs) represent a promising strategy for treatment and prevention of CIN, due to their ability to deliver CM during diagnosis imaging. In this study, iohexol-containing liposomes were produced using microfluidic technique for first time. Several phosphocholine lipids (e.g. DMPC, DOPC, DPPC and DSPC) with cholesterol (2:1 ratio) were investigated and DLS, FTIR and in vitro release studies at 37 °C were performed, with stability studies conducted on the best formulation. The microfluidic method allowed to obtain a high encapsulation efficiency (over 70%), and release profiles showed an iohexol release around or less than 0.12 mg/ml after 2 h for the majority of the formulations, which is not toxic to the kidney cells

Isatin thiosemicarbazone-blended polymer films for biomedical applications : surface morphology, characterisation and preliminary biological assessment

Poly (methyl methacrylate) and polyurethane are polymers currently used for a range of biomedical applications. To modify their surface characteristics, biocompatibility and potentially reduce any related side effects the addition to the polymers of appropriate compounds has been investigated. Isatin thiosemicarbazone derivatives were synthesised and added to poly (methyl methacrylate) and polyurethane solutions before spin coating them on to a silica wafer. The resultant films were characterised with contact angle goniometry and atomic force microscopy. PMMA films produced from tetrahydrofuran solvent displayed honeycombed structures which were highly hydrophobic; however, such changes were not seen for polyurethane surfaces. The cytotoxicity and effect on cell proliferation of polymer surfaces were investigated using PNT2A prostate cells. The isatin-containing polymers were deemed non-toxic at the concentrations used, while cell proliferation studies suggested that the resulting films were supportive of cell growth

A novel PAA derivative with enhanced drug efficacy in pancreatic cancer cell lines.

Nanoparticles have been shown to be effective drug carriers in cancer therapy. Pancreatic cancer forms dense tumours which are often resistant to drug molecules. In order to overcome such multidrug resistance, new drug entities, novel delivery systems and combination therapy strategies are being explored. In this paper, we report the design and synthesis of a poly(allylamine)-based amphiphile modified with hydrophobic naphthalimido pendant groups. Bisnaphthalimide compounds have been shown to possess anticancer activity. The potential of this polymer to encapsulate, solubilize and enhance drug (5-fluorouricil and bis-(naphthalimidopropyl)-diaminooctane) cytotoxicity in BxPC-3 cells was evaluated. Our studies showed that the insoluble drugs could be formulated up to 4.3 mg mL−1 and 2.4 mg mL−1 inside the amphiphiles, respectively. Additionally, the novel poly(allylamine)-naphthalimide carrier resulted in an amplification of cytotoxic effect with drug treatment after 24 h, and was capable of reduction of 50% cell population at concentrations as low as 3 μg mL−1