Characterization of leaf-level particulate matter for an industrial city using electron microscopy and X-ray microanalysis.

This study reports application of monitoring and characterization protocol for particulate matter (PM) deposited on tree leaves, using Quercus ilex as a case study species. The study area is located in the industrial city of Terni in central Italy, with high PM concentrations. Four trees were selected as representative of distinct pollution environments based on their proximity to a steel factory and a street. Wash off from leaves onto cellulose filters were characterized using scanning electron microscopy and energy dispersive X-ray spectroscopy, inferring the associations between particle sizes, chemical composition, and sampling location. Modeling of particle size distributions showed a tri-modal fingerprint, with the three modes centered at 0.6 (factory related), 1.2 (urban background), and 2.6µm (traffic related). Chemical detection identified 23 elements abundant in the PM samples. Principal component analysis recognized iron and copper as source-specific PM markers, attributed mainly to industrial and heavy traffic pollution respectively. Upscaling these results on leaf area basis provided a useful indicator for strategic evaluation of harmful PM pollutants using tree leaves.

Development of multi-functional streetscape green infrastructure using a performance index approach.

This paper presents a performance evaluation framework for streetscape vegetation. A performance index (PI) is conceived using the following seven traits, specific to the street environments - Pollution Flux Potential (PFP), Carbon Sequestration Potential (CSP), Thermal Comfort Potential (TCP), Noise Attenuation Potential (NAP), Biomass Energy Potential (BEP), Environmental Stress Tolerance (EST) and Crown Projection Factor (CPF). Its application is demonstrated through a case study using fifteen street vegetation species from the UK, utilising a combination of direct field measurements and inventoried literature data. Our results indicate greater preference to small-to-medium size trees and evergreen shrubs over larger trees for streetscaping. The proposed PI approach can be potentially applied two-fold: one, for evaluation of the performance of the existing street vegetation, facilitating the prospects for further improving them through management strategies and better species selection; two, for planning new streetscapes and multi-functional biomass as part of extending the green urban infrastructure.

National climate policies across Europe and their impacts on cities strategies.

Globally, efforts are underway to reduce anthropogenic greenhouse gas emissions and to adapt to climate change impacts at the local level. However, there is a poor understanding of the relationship between city strategies on climate change mitigation and adaptation and the relevant policies at national and European level. This paper describes a comparative study and evaluation of cross-national policy. It reports the findings of studying the climate change strategies or plans from 200 European cities from Austria, Belgium, Estonia, Finland, France, Germany, Ireland, Italy, Netherlands, Spain and the United Kingdom. The study highlights the shared responsibility of global, European, national, regional and city policies. An interpretation and illustration of the influences from international and national networks and policy makers in stimulating the development of local strategies and actions is proposed. It was found that there is no archetypical way of planning for climate change, and multiple interests and motivations are inevitable. Our research warrants the need for a multi-scale approach to climate policy in the future, mainly ensuring sufficient capacity and resource to enable local authorities to plan and respond to their specific climate change agenda for maximising the management potentials for translating environmental challenges into opportunities.

Progressive development in experimental models of transungual drug delivery of anti-fungal agents.

Pre-clinical development comprises of different procedures that relate drug discovery in the laboratory for commencement of human clinical trials. Pre-clinical studies can be designed to recognize a lead candidate from a list to develop the procedure for scale-up, to choose the unsurpassed formulation, to determine the frequency, and duration of exposure; and eventually make the foundation of the anticipated clinical trial design. The foremost aim in the pharmaceutical research and industry is the claim of drug product quality throughout a drug's life cycle. The particulars of the pre-clinical development process for different candidates may vary; however, all have some common features. Typically in vitro, in vivo or ex vivo studies are elements of pre-clinical studies. Human pharmacokinetic in vivo studies are often supposed to serve as the 'gold standard' to assess product performance. On the other hand, when this general assumption is revisited, it appears that in vitro studies are occasionally better than in vivo studies in assessing dosage forms. The present review is compendious of different such models or approaches that can be used for designing and evaluation of formulations for nail delivery with special reference to anti-fungal agents.

Assessment and mitigation of the environmental burdens to air from land applied food-based digestate.

Anaerobic digestion (AD) of putrescible urban waste for energy recovery has seen rapid growth over recent years. In order to ascertain its systems scale sustainability, however, determination of the environmental fate of the large volume of digestate generated during the process is indispensable. This paper evaluates the environmental burdens to air associated with land applied food-based digestate in terms of primary pollutants (ammonia, nitrogen dioxide) and greenhouse gases (methane and nitrous oxide). The assessments have been made in two stages - first, the emissions from surface application of food-based digestate are quantified for the business as usual (BAU). In the next step, environmental burden minimisation potentials for the following three mitigation measures are estimated - mixed waste digestate (MWD), soil-incorporated digestate (SID), and post-methanated digestate (PMD). Overall, the mitigation scenarios demonstrated considerable NH3, CH4 and N2O burden minimisation potentials, with positive implications for both climate change and urban pollution.

A rare case of isolated hydatid cyst of breast.

INTRODUCTION: Hydatid cyst of the breast is very rare. It is challenging to differentiate it from other tumoral lesions of the breast. Only few reports of breast hydatid cyst are published and majority of the reported cases have been diagnosed postoperatively as it is not possible to reach definitive diagnosis with clinical examination and radiological investigations only. PRESENTATION OF CASE: A 31-year old woman presented with a painless lump in the right breast since one year duration. On clinical examination, a non-mobile, firm lump was detected in the right breast associated with nipple retraction, but there was no axillary lymphadenopathy. This case was diagnosed as hydatid cyst incidentally during surgery from its gross appearance which mimics that of a liver hydatid cyst, normally common in this endemic area. DISCUSSION: Hydatid disease is a parasitic infection caused by the larval form of Echinococcus granulosus and seen endemically among sheep-raising communities. The breast can be a primary site or part of a disseminated hydatidosis. It might mimic fibroadenoma, phyllodes tumors, chronic abscesses, or even carcinoma. Preoperative diagnosis can be made by fine needle aspiration cytology. It also can be diagnosed by radiological or serologic means but neither of them is definitive. Surgery is the treatment of choice. CONCLUSION: Hydatid cyst of the breast is very uncommon but it should be included in differential diagnosis of breast lumps for patients living in endemic areas.

Tamarindus indica pectin blend film composition for coating tablets with enhanced adhesive force strength.

Tablet coating is the most useful method to improve tablet texture, odour and mask taste. Thus, the present investigation was aimed at developing an industrially acceptable aqueous tablet coating material. The physico-chemical, electrical and SEM investigations ensures that blending of Tamarindus indica (Linn.) pectin (TP) with chitosan gives water resistant film texture. Therefore, CH-TP (60:40) spray coated tablets were prepared. The evaluation of CH-TP coated tablets showed enhanced adhesive force strength (between tablet surface to coat) and negligible cohesive force strength (between two tablets) both evaluated using texture analyzer. The comparison of CH-TP coated tablets with Eudragit coated tablets further supported superiority of the former material. Thus, the findings pointed towards the potential of CH-TP for use as a tablet coating material in food as well as pharmaceutical industry.

Spray dried chitosan-EDTA superior microparticles as solid substrate for the oral delivery of amphotericin B.

The present investigation was aimed at synthesis of chitosan-EDTA superior microparticles (COECH) bearing high oil adsorbing and oil desorbing properties. These superior particles were prepared by thermal amide conjugation of COO(-) group of EDTA with NH2 group of chitosan employing spray-drying technique. The synthesis was optimized using 4(2) full factorial design. The particles showed high oil adsorbing capacity as well as oil desorbing capacity with enhanced dispersive components of surface free energy as compared to Aerosil 200. In addition, these COECH microparticles showed higher amphotericin B loading capacity, enhancement in the in vitro dissolution performance (12-fold) and produces nanoemulsion in the size range of 70-90 nm. Further, the results were in consonance with those observed during ex vivo performance. Thus, the findings revealed simple synthesis of COECH microparticles that showed superior properties of solid substrate for the development of amphotericin B nanoemulsion.

Ethylenediaminediacetic acid bis(carbido amide chitosan): synthesis and evaluation as solid carrier to fabricate nanoemulsion.

We have optimized the synthesis of spray dried ethylenediaminediacetic acid bis(carbido amide chitosan) (ED-chitosan) microparticles employing 3(2) full factorial design. The ED-chitosan microparticles were characterized using FTIR-ATR, DSC analysis, oil adsorbing capacity, oil desorbing capacity, surface free energy and dynamic advancing contact angle. The ED-chitosan microparticles were found to have enhanced dispersive component of surface free energy as compared to Aerosil 200. However, they showed lower polar component. This was associated with similar oil adsorbing capacity but higher desorbing capacity. The SEM analysis supported ability of ED-chitosan microparticles to completely spread lipophillic drug over its surface. The reconstituted nanoemulsion generated from ED-chitosan was stable (neutral zeta potential), spherical shaped and 110 nm size (TEM analysis). Further, these nanoemulsions when prepared with primaquine were successfully enhanced in vitro dissolution and its ex vivo performance. Thus, the study showed new possibilities of industrial acceptance of ED-chitosan microparticles as a solid carrier for the fabrication of nanoemulsion.

Aegle marmelos fruit pectin for food and pharmaceuticals: Physico-chemical, rheological and functional performance.

Pectin is used in a number of foods as a gelling agent, thickener, texturizer, emulsifier and stabilizer. Bael fruit, obtained from Aegle marmelos, is a rich source of pectin. Bael fruit pectin (BFP) was extracted from ripe Bael fruits. The process yielded 15% (w/w) pure BFP. The swelling index decreased in the following order: water>pH 7.4>pH 6.8>pH 1.2>HCl (0.1N). Galacturonic acid content of 87.8%, degree of esterification of 47.2%, 17.3% methoxy groups, 0.29% acetyl groups and equivalent weight of 1209.5, indicate it to be a good gelling agent and easily amenable to derivatization. BFP exhibited a significant concentration-dependent prolongation of prothrombin time. The absence of hemagglutinating activity and antinutritional factors coupled with the activity to confer better emulsion capacity, stability and antimicrobial activity gives BFP a clear edge over commercial citrus pectin (CP) for exploitation as an additive in food and pharmaceuticals.

Exploiting the synergistic effect of chitosan-EDTA conjugate with MSA for the early recovery from colitis.

The present study was aimed to exploit the antibacterial/antifungal and film coating potential of Chitosan-EDTA (CH-EDTA) conjugate in combination with mesalamine (anti-inflammatory agent) for the early recovery from TNBS induced coilitis. The results suggested CH:EDTA (1:1) spray coated mesalamine tablets has an ability to transport drug in buffer pH 6.8 with rat caecal content condition. The CH-EDTA shows high level of adhesiveness of coat with core tablet. Further, FTIR, DSC and SEM analysis suggested spray coating of CH-EDTA on tablets was beneficial as compared to ladling method as it enhances interaction density and showed resistance from pH (1.2, 6.8 and 7.4). The pharmacokinetic parameters, AUC and AUMC of spray coated tablets were respectively, 4.70 fold and 2.10 fold increased. A synergistic therapeutic effect with CH-EDTA spray coated mesalamine was observed as evaluated by colon/body weight ratio, clinical activity score and damage score. X ray image study supported that CH-EDTA conjugate successfully delivered MSA tablets to large intestine. Histopathology of colon tissues showed rapid recovery from TNBS induced colitis in rats within 4 days. The findings revealed decreased recovery period was due to combined effect of both CH-EDTA and MSA to treat TNBS induced colitis.

An insight into the properties of Aegle marmelos pectin-chitosan cross-linked films.

Pectin of Aegle marmelos (AP) ripe fruits processed in equal proportion with chitosan (CH) formed films that exhibited minimum swelling index and volume index on exposure to buffers of acidic and alkaline pH. Highest contact angle and spreading coefficient coupled with lowest work of adhesion in all buffers for this film suggested availability of limited number of functional groups for interaction with water molecules due to optimum cross-linking between -NH(3)(+) groups of CH and -COO(-) groups of AP. This contention was substantiated by the presence of almost negligible charge on this film. The endothermic transition ΔH characteristic of -NH(3)(+)-COO(-) cross-linking between groups in this film was observed to decrease by only 1% after its sequential exposure to pH 1.2 (3 h) and pH 7.4 (6 h). Furthermore, the absence of pores or erosion in the scanning electron photomicrograph suggested the versatility of this film due to its resistance to acidic and alkaline pH.

Chitosan films: crosslinking with EDTA modifies physicochemical and mechanical properties.

The present study was aimed to develop chitosan-EDTA films and evaluate their physico-chemical and mechanical properties. The physical properties suggested lowest swelling, volume and volume index of films prepared by employing equal weight of chitosan (CH) and EDTA (1.5% w/v). The CH:EDTA film (1:l, on weight basis) showed minimum contact angle, work of adhesion and high negative spreading coefficient indicating lipophilic behavior of film. Further, the FTIR and DSC analysis suggested maximum crosslinking density in film prepared with equal proportion of CH and EDTA. The mechanical properties explored using texture analyzer revealed increasing the proportions of EDTA rendered the films more flexible and decreased their hardness. Furthermore, in vitro permeation of 5-FU and mesalamine with different solubilities showed minimum permeation across CH­EDTA (1:1) film, indicating high crosslinking density that decreased void space inside the film. Hence, the CH­EDTA conjugate could be considered to be possess great potential for various pharmaceutical applications such as film based delivery systems, controlled and sustained delivery systems etc.

Optimisation of novel method for the extraction of steviosides from Stevia rebaudiana leaves.

Stevioside, a diterpene glycoside, is well known for its intense sweetness and is used as a non-caloric sweetener. Its potential widespread use requires an easy and effective extraction method. Enzymatic extraction of stevioside from Stevia rebaudiana leaves with cellulase, pectinase and hemicellulase, using various parameters, such as concentration of enzyme, incubation time and temperature, was optimised. Hemicellulase was observed to give the highest stevioside yield (369.23±0.11µg) in 1h in comparison to cellulase (359±0.30µg) and pectinases (333±0.55µg). Extraction from leaves under optimised conditions showed a remarkable increase in the yield (35 times) compared with a control experiment. The extraction conditions were further optimised using response surface methodology (RSM). A central composite design (CCD) was used for experimental design and analysis of the results to obtain optimal extraction conditions. Based on RSM analysis, temperature of 51-54°C, time of 36-45min and the cocktail of pectinase, cellulase and hemicellulase, set at 2% each, gave the best results. Under the optimised conditions, the experimental values were in close agreement with the prediction model and resulted in a three times yield enhancement of stevioside. The isolated stevioside was characterised through 1H-NMR spectroscopy, by comparison with a stevioside standard.

Evaluation of biosafety and intracellular uptake of Cremophor EL free paclitaxel elastic liposomal formulation.

The present study examines the acute, sub-acute toxicity, and cytotoxicity of paclitaxel elastic liposomal formulation in comparison to a marketed Cremophor EL (polyoxyethylated castor oil):ethanol (1:1, v/v) based formulation. In the previous study, Cremophor EL free paclitaxel elastic liposomal formulation was developed and characterized. Cytotoxicity of formulation was evaluated by MTT assay using A549 cell lines. Percentage intracellular uptake of paclitaxel elastic liposomal and marketed formulation was determined using a fluorescence activating cell sorting assay (FACS) and fluorescence microscopy techniques. Single and repeated dose toxicity measurement showed no mortality, hematological, biochemical, or histopathological changes up to a dose of 120 mg/kg for paclitaxel elastic liposomal formulation, in comparison the marketed formulation showed toxicity at a dose of 40 mg/kg. Maximum tolerated dose (MTD) for paclitaxel elastic liposomal and marketed formulation was found to be 160 mg/kg and 40 mg/kg, respectively. Results of FACS analysis showed a 94.6 ± 2.5% intracellular uptake of fluorescence marker acridine orange (AO) loaded in elastic liposomes; in comparison the AO solution showed only a 19.8 ± 1.1% uptake. Paclitaxel elastic liposomal formulation seems to be a better alternative for safe and effective delivery of paclitaxel. This study proves the safety and higher intracellular uptake of paclitaxel elastic liposomal formulation.

Localized delivery of paclitaxel using elastic liposomes: formulation development and evaluation.

In the present study an elastic liposomes-based paclitaxel formulation was developed with the objective to remove Cremophor EL. Cremophor EL is currently used for solubilizing paclitaxel in the marketed formulation and is known to produce toxic effects. Elastic liposomal paclitaxel formulation was extensively characterized in vitro, ex-vivo, and in vivo. The results obtained were compared against the marketed paclitaxel formulation. The maximum amount of paclitaxel loaded in the elastic liposomal formulation was found to be 6.0 mg/ml, which is similar to the commercial strength of marketed paclitaxel formulation. In vitro skin permeation and deposition studies showed 10.8-fold enhanced steady state transdermal flux and 15.0-fold enhanced drug deposition in comparison to drug solution. These results further confirmed with the vesicle-skin interaction study using FTIR technique. Results of the hemolytic toxicity assay indicate that elastic liposomal formulation induced only 11.2 ± 0.2% hemolysis in comparison to the commercial formulation which showed 38 ± 3.0%. Further, results of the Draize test showed no skin irritation of paclitaxel elastic liposomal formulation. Findings of the study demonstrate that elastic liposomes as a carrier is an attractive approach for localized delivery of paclitaxel.

Development and evaluation of mathematical model to predict disintegration time of fast disintegrating tablets using powder characteristics.

The objective of the study was to develop a mathematical model for predicting the disintegration time of fast disintegrating tablets (FDTs) by estimating the powder characteristics of powder blend prior to compression. A combination of chitosan-alginate complex and glycine in the ratio of 50:50 was used for preparing FDTs. The developed mathematical model allowed water sorption time (WST), effective pore radius (R(eff.p)) and swelling Index (SI) of powder mixture as well as tablet crushing strength to be successfully correlated with disintegration time (DT) of FDTs. The predicted model showed that disintegration time of FDTs to be directly correlated with powder characteristics and inversely correlated with tablet crushing strength. Furthermore, a correlation of 0.97 was obtained when DT of FDTs was compared with SI/(WST * R(eff.p)). This correlation was not affected by inclusion of water soluble (ondansetron hydrochloride or metaclopramide hydrochloride) or water insoluble (domperidone) drugs in the powder blend or FDTs. These observations indicated the versatility of the mathematical model in predicting the disintegration time of FDTs by evaluating the selected characteristics of the powder blends without actually preparing the FDTs.

Efficacy and toxicological studies of cremophor EL free alternative paclitaxel formulation.

PURPOSE: In the present study, Cremophor EL free paclitaxel elastic liposomal formulation consisting of soya phosphatidylcholine and biosurfactant sodium deoxycholate was developed and optimized. The toxicological profile, antitumor efficacy and hemolytic toxicity of paclitaxel elastic liposomal formulation in comparison to Cremophor EL based marketed formulation were evaluated. METHODS: Paclitaxel elastic liposomal formulations were prepared and characterized in vitro, ex-vivo and in vivo. Single dose toxicity study of paclitaxel elastic liposomal and marketed formulation was carried out in dose range of 10, 20, 40, 80, 120, 160 and 200 mg/kg. Cytotoxicity of developed formulation was evaluated using small cell lung cancer cell line (A549). Antitumor activity of developed formulation was compared with the marketed formulation using Cytoselect™ 96-well cell transformation assay. RESULTS: In vivo administration of paclitaxel elastic liposomal formulation into mice showed 6 fold increase in Maximum Tolerated Dose (MTD) in comparison to the marketed formulation. Similarly, LD50 (141.6 mg/kg) was also found to increase significantly than the marketed formulation (16.7 mg/kg). Result of antitumor assay revealed a high reduction of tumor density with paclitaxel elastic liposomal formulation. Reduction in hemolytic toxicity was also observed with paclitaxel elastic liposomal formulation in comparison to the marketed formulation. CONCLUSION: The carrier based approach for paclitaxel delivery demonstrated significant reduction in toxicity as compared to the Cremophor EL based marketed formulation following intra-peritoneal administration in mice model. The reduced toxicity and enhanced anti-cancer activity of elastic liposomal formulation strongly indicate its potential for safe and effective delivery of paclitaxel.

Development of Spectrofluorimetric and HPLC Methods for In vitro Analysis of Repaglinide.

Spectrofluorimetric and high-performance liquid chromatography methods for estimation of repaglinide were developed. These methods were validated for estimation of repaglinide in tablets as well as in receptor fluid obtained during in vitro permeation studies. Repaglinide was observed to exhibit emission and excitation wavelengths, respectively, at 379 nm and 282 nm with linearity in the concentration range of 5-80 µg/ml. High-performance liquid chromatography analysis of repaglinide yielded retention time of 6.14 min with linearity ranging from 0.1-1.2 µg/ml concentration. Spectrofluorimetric analysis of repaglinide in tablets yielded results comparable to high performance liquid chromatography.