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1.
Pharm Dev Technol ; 28(8): 724-742, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37493413

RESUMO

In the present study, novel gastroretentive bilayer tablets were developed that are promising for the once-a-day oral delivery of the drug candidate MT-1207. The gastroretentive layer consisted of a combination of hydrophilic and hydrophobic polymers, namely polyethylene oxide and Kollidon® SR. A factorial experiment was conducted, and the results revealed a non-effervescent gastroretentive layer that, unlike most gastroretentive layers reported in the literature, was easy to prepare, and provided immediate tablet buoyancy (mean floating lag time of 1.5 s) that lasted over 24 h in fasted state simulated gastric fluid (FaSSGF) pH 1.6, irrespective of the drug layer, thereby allowing a 24-hour sustained release of MT-1207 from the drug layer of the tablets. Furthermore, during in vitro buoyancy testing of the optimised bilayer tablets in media of different pH values (1.0, 3.0, 6.0), the significant difference (one-way ANOVA, p < 0.001) between the respective total floating times indicated that stomach pH effects on tablet buoyancy are important to be considered during the development of non-effervescent gastroretentive formulations and the choice of dosing regimen. To the best of our knowledge, this has not been reported before, and it should probably be factored in when designing dosing regimens. Finally, a pharmacokinetic study in Beagle dogs indicated a successful in vivo 24-hour sustained release of MT-1207 from the optimised gastroretentive bilayer tablet formulations with the drug plasma concentration remaining above the estimated minimum effective concentration of 1 ng/mL at the 24-hour timepoint and also demonstrated the gastroretentive capabilities of the hydrophilic and hydrophobic polymer combination. The optimised formulations will be forwarded to clinical development.


Assuntos
Polímeros , Animais , Cães , Preparações de Ação Retardada/química , Polímeros/química , Solubilidade , Comprimidos/química
2.
Mol Phylogenet Evol ; 176: 107584, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35843570

RESUMO

Remote oceanic islands of the Pacific host elevated levels of actinopterygian (ray-finned fishes) endemism. Characterizing the evolutionary histories of these endemics has provided insight into the generation and maintenance of marine biodiversity in many regions. The subtropical islands of Lord Howe, Norfolk, and Rangitahua (Kermadec) in the Southwest Pacific are yet to be comprehensively studied. Here, we characterize the spatio-temporal diversification of marine fishes endemic to these Southwest Pacific islands by combining molecular phylogenies and the geographic distribution of species. We built Bayesian ultrametric trees based on open-access and newly generated sequences for five mitochondrial and ten nuclear loci, and using fossil data for time calibration. We present the most comprehensive phylogenies to date for marine ray-finned fish genera, comprising 34 species endemic to the islands, including the first phylogenetic placements for 11 endemics. Overall, our topologies confirm the species status of all endemics, including three undescribed taxa. Our phylogenies highlight the predominant affinity of these endemics with the Australian fish fauna (53%), followed by the East Pacific (15%), and individual cases where the closest sister taxon of our endemic is found in the Northwest Pacific and wider Indo-Pacific. Nonetheless, for a quarter of our focal endemics, their geographic affinity remains unresolved due to sampling gaps within their genera. Our divergence time estimates reveal that the majority of endemic lineages (67.6%) diverged after the emergence of Lord Howe (6.92 Ma), the oldest subtropical island in the Southwest Pacific, suggesting that these islands have promoted diversification. However, divergence ages of some endemics pre-date the emergence of the islands, suggesting they may have originated outside of these islands, or, in some cases, ages may be overestimated due to unsampled taxa. To fully understand the role of the Southwest Pacific subtropical islands as a 'cradle' for diversification, our study advocates for further regional surveys focused on tissue collection for DNA analysis.


Assuntos
Biodiversidade , Peixes , Animais , Austrália , Teorema de Bayes , Peixes/genética , Filogenia
3.
Pharm Dev Technol ; 26(3): 349-361, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33430679

RESUMO

Hypertension is one of the most common chronic cardiovascular disorders. Sustained-release formulations are developed to maintain drug therapeutic levels throughout the treatment of hypertension, to promote patient compliance and improve patient outcomes. We have developed and tested in in vivo trials a once-a-day tablet formulation for the novel antihypertensive drug MT-1207. The tablets based upon a hydrophilic polymer matrix underwent post-compression parameter and physicochemical characterisations, along with in vitro drug release testing. The most promising formulation containing 31% w/w HPMC K15M gave a 24-hour release of MT-1207 with an almost constant release rate up to 20 hours. Follow in in vivo studies were carried out in Beagle dogs for the optimised sustained-release tablets in comparison to immediate-release tablets. The results showed that a sustained release of MT-1207 from the new formulation was achieved with a drug t1/2 2-2.5 times longer than the immediate-release tablets. Moreover, the AUC0-24h values of both sustained- and immediate-release tablets were identical at the same dose of 30 mg, indicating that the same amount of drug was absorbed in each case. For treatments based upon MT-1207, this development is significant for future commercial exploitation via scale-up and further trials, and for improved patient outcomes.


Assuntos
Anti-Hipertensivos/administração & dosagem , Preparações de Ação Retardada/química , Animais , Anti-Hipertensivos/sangue , Cães , Liberação Controlada de Fármacos , Feminino , Derivados da Hipromelose/química , Masculino , Solubilidade , Comprimidos
4.
J Anim Ecol ; 89(2): 309-322, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31646627

RESUMO

Understanding patterns and processes governing biodiversity along broad-scale environmental gradients, such as depth or latitude, requires an assessment of not just taxonomic richness, but also morphological and functional traits of organisms. Studies of traits can help to identify major selective forces acting on morphology. Currently, little is known regarding patterns of variation in the traits of fishes at broad spatial scales. The aims of this study were (a) to identify a suite of key traits in marine fishes that would allow assessment of morphological variability across broad-scale depth (50-1200 m) and latitudinal (29.15-50.91°S) gradients, and (b) to characterize patterns in these traits across depth and latitude for 144 species of ray-finned fishes in New Zealand waters. Here, we describe three new morphological traits, namely fin-base-to-perimeter ratio, jaw-length-to-mouth-width ratio, and pectoral-fin-base-to-body-depth ratio. Four other morphological traits essential for locomotion and food acquisition that are commonly measured in fishes were also included in the study. Spatial ecological distributions of individual fish species were characterized in response to a standardized replicated sampling design, and morphological measurements were obtained for each species from preserved museum specimens. With increasing depth, fishes, on average, became larger and more elongate, with higher fin-base-to-perimeter ratio and larger jaw-length-to-mouth-width ratio, all of which translates into a more eel-like anguilliform morphology. Variation in mean trait values along the depth gradient was stronger at lower latitudes for fin-base-to-perimeter ratio, elongation and total body length. Average eye size peaked at intermediate depths (500-700 m) and increased with increasing latitude at 700 m. These findings suggest that, in increasingly extreme environments, fish morphology shifts towards a body shape that favours an energy-efficient undulatory swimming style and an increase in jaw-length vs. mouth width for opportunistic feeding. Furthermore, increases in eye size with both depth and latitude indicate that changes in both the average ambient light conditions as well as seasonal variations in day-length can act to select ecomorphological adaptations in fishes.


Assuntos
Biodiversidade , Peixes , Animais , Locomoção , Nova Zelândia , Fenótipo
5.
Sensors (Basel) ; 20(19)2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32992886

RESUMO

Recent developments in the area of condition monitoring research have been targeted towards predicting machinery health condition for the purpose of preventative maintenance. Typically, published research uses data collected from rotating components (bearings, cutting tools, etc.) working in an idealized lab environment as the case study for prognosis algorithm validations. However, the operational implementation in industry is still very sporadic, mainly owing to the lack of proper data allowing sufficiently mature development of comprehensive methodologies. The prognosis methodology presented herein bridges the gap between academic research and industrial implementations by employing a novel time period for prognosis and implementing random coefficients regression models. The definition of the remaining maintenance-free operating period (RMFOP) is proposed first, which helps to transform the usefulness of the degradation data that is readily available from data short of failure. Degradation patterns are subsequently extracted from the original degradation data, before fitting into either of two regression models (linear or exponential). The system residual life distributions are then computed and updated by estimating the parameter statistics within the model. This RMFOP-based methodology is validated using real-world degradation data collected from multiple operational railway switch systems across Great Britain. The results indicate that both the linear model and the exponential model can produce residual life distributions with a sufficient prediction accuracy for this specific application. The exponential model gives better predictions, the accuracy of which also improves as more of system life percentage has elapsed. By using the RMFOP methodology, switch system health condition affected by an incipient overdriving fault is recognized and predicted.

6.
Pharm Dev Technol ; 24(4): 504-512, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30132723

RESUMO

This study describes the properties of an amphotericin B-containing mucoadhesive nanostructured lipid carrier (NLC), with the intent to maximize uptake within the gastrointestinal tract. We have reported previously that lipid nanoparticles can significantly improve the oral bioavailability of amphotericin B (AmpB). On the other hand, the aggregation state of AmpB within the NLC has been ascribed to some of the side effects resulting from IV administration. In the undissolved state, AmpB (UAmpB) exhibited the safer monomeric conformation in contrast to AmpB in the dissolved state (DAmpB), which was aggregated. Chitosan-coated NLC (ChiAmpB NLC) presented a slightly slower AmpB release profile as compared to the uncoated formulation, achieving 26.1% release in 5 hours. Furthermore, the ChiAmpB NLC formulation appeared to prevent the expulsion of AmpB upon exposure to simulated gastrointestinal pH media, whereby up to 63.9% of AmpB was retained in the NLC compared to 56.1% in the uncoated formulation. The ChiAmpB NLC demonstrated mucoadhesive properties in pH 5.8 and 6.8. Thus, the ChiAmpB NLC formulation is well-primed for pharmacokinetic studies to investigate whether delayed gastrointestinal transit may be exploited to improve the systemic bioavailability of AmpB, whilst simultaneously addressing the side-effect concerns of AmpB.


Assuntos
Adesivos/química , Anfotericina B/química , Quitosana/química , Portadores de Fármacos/química , Nanoestruturas/química , Adesivos/administração & dosagem , Administração Oral , Anfotericina B/administração & dosagem , Antibacterianos/administração & dosagem , Antibacterianos/química , Quitosana/administração & dosagem , Portadores de Fármacos/administração & dosagem , Lipídeos , Nanoestruturas/administração & dosagem
7.
AAPS PharmSciTech ; 20(3): 136, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30838459

RESUMO

Surface-modified nanostructured lipid carriers (NLC) represent a promising mode of drug delivery used to enhance retention of drugs at absorption site. Formulated chitosan-coated amphotericin-B-loaded NLC (ChiAmp NLC) had a size of 394.4 ± 6.4 nm, encapsulation and loading efficiencies of 86.0 ± 3% and 11.0 ± 0.1% respectively. Amphotericin-B release from NLCs was biphasic with no changes in physical properties upon exposure to simulated gastrointestinal conditions. Antifungal properties of Amphotericin-B and ChiAmpB NLC were comparable but ChiAmpB NLC was twice less toxic to red blood cells and ten times safer on HT-29 cell lines. In vitro mucoadhesion data were observed ex vivo, where ChiAmpB NLC resulted in higher retention within the small intestine compared to the uncoated formulation. The data strongly offers the possibility of orally administering a non-toxic, yet effective Amphotericin-B nanoformulation for the treatment of systemic fungal infections.


Assuntos
Anfotericina B/administração & dosagem , Anfotericina B/farmacologia , Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Quitosana/administração & dosagem , Quitosana/farmacologia , Portadores de Fármacos/química , Lipídeos/química , Nanoestruturas/química , Administração Oral , Anfotericina B/química , Animais , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Quitosana/química , Eritrócitos/efeitos dos fármacos , Células HT29 , Humanos , Mucosa Intestinal/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Ratos Sprague-Dawley
8.
Mol Pharm ; 15(5): 1826-1841, 2018 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-29533634

RESUMO

Solid dispersions can be a successful way to enhance the bioavailability of poorly soluble drugs. Here 60 solid dispersion formulations were produced using ten chemically diverse, neutral, poorly soluble drugs, three commonly used polymers, and two manufacturing techniques, spray-drying and melt extrusion. Each formulation underwent a six-month stability study at accelerated conditions, 40 °C and 75% relative humidity (RH). Significant differences in times to crystallization (onset of crystallization) were observed between both the different polymers and the two processing methods. Stability from zero days to over one year was observed. The extensive experimental data set obtained from this stability study was used to build multiple linear regression models to correlate physicochemical properties of the active pharmaceutical ingredients (API) with the stability data. The purpose of these models is to indicate which combination of processing method and polymer carrier is most likely to give a stable solid dispersion. Six quantitative mathematical multiple linear regression-based models were produced based on selection of the most influential independent physical and chemical parameters from a set of 33 possible factors, one model for each combination of polymer and processing method, with good predictability of stability. Three general rules are proposed from these models for the formulation development of suitably stable solid dispersions. Namely, increased stability is correlated with increased glass transition temperature ( Tg) of solid dispersions, as well as decreased number of H-bond donors and increased molecular flexibility (such as rotatable bonds and ring count) of the drug molecule.


Assuntos
Preparações Farmacêuticas/química , Polímeros/química , Disponibilidade Biológica , Química Farmacêutica/métodos , Cristalização/métodos , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Estabilidade de Medicamentos , Modelos Lineares , Solubilidade/efeitos dos fármacos , Temperatura de Transição
9.
AAPS PharmSciTech ; 19(8): 3403-3413, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30097806

RESUMO

An extrusion-based 3D printer was used to fabricate paracetamol tablets with different geometries (mesh, ring and solid) from a single paste-based formulation formed from standard pharmaceutical ingredients. The tablets demonstrate that tunable drug release profiles can be achieved from this single formulation even with high drug loading (> 80% w/w). The tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed well-defined release profiles (from immediate to sustained release) controlled by their different geometries. The dissolution results showed dependency of drug release on the surface area/volume (SA/V) ratio and the SA of the different tablets. The tablets with larger SA/V ratios and SA had faster drug release. The 3D printed tablets were also evaluated for physical and mechanical properties including tablet dimension, drug content, weight variation and breaking force and were within acceptable range as defined by the international standards stated in the US Pharmacopoeia. X-ray powder diffraction, differential scanning calorimetry and attenuated total reflectance Fourier transform infrared spectroscopy were used to identify the physical form of the active and to assess possible drug-excipient interactions. These data again showed that the tablets meet USP requirement. These results clearly demonstrate the potential of 3D printing to create unique pharmaceutical manufacturing, and potentially clinical, opportunities. The ability to use a single unmodified formulation to achieve defined release profiles could allow, for example, relatively straightforward personalization of medicines for individuals with different metabolism rates for certain drugs and hence could offer significant development and clinical opportunities.


Assuntos
Acetaminofen/química , Acetaminofen/farmacocinética , Liberação Controlada de Fármacos , Impressão Tridimensional , Tecnologia Farmacêutica/métodos , Varredura Diferencial de Calorimetria , Composição de Medicamentos/métodos , Excipientes/química , Espectroscopia de Infravermelho com Transformada de Fourier , Comprimidos/química , Difração de Raios X
10.
Mol Pharm ; 14(4): 959-973, 2017 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-28206770

RESUMO

Fluid bed coating has been shown to be a suitable manufacturing technique to formulate poorly soluble drugs in glass solutions. Layering inert carriers with a drug-polymer mixture enables these beads to be immediately filled into capsules, thus avoiding additional, potentially destabilizing, downstream processing. In this study, fluid bed coating is proposed for the production of controlled release dosage forms of glass solutions by applying a second, rate controlling membrane on top of the glass solution. Adding a second coating layer adds to the physical and chemical complexity of the drug delivery system, so a thorough understanding of the physical structure and phase behavior of the different coating layers is needed. This study aimed to investigate the surface and cross-sectional characteristics (employing scanning electron microscopy (SEM) and time of flight secondary ion mass spectrometry (ToF-SIMS)) of an indomethacin-polyvinylpyrrolidone (PVP) glass solution, top-coated with a release rate controlling membrane consisting of either ethyl cellulose or Eudragit RL. The implications of the addition of a pore former (PVP) and the coating medium (ethanol or water) were also considered. In addition, polymer miscibility and the phase analysis of the underlying glass solution were investigated. Significant differences in surface and cross-sectional topography of the different rate controlling membranes or the way they are applied (solution vs dispersion) were observed. These observations can be linked to the polymer miscibility differences. The presence of PVP was observed in all rate controlling membranes, even if it is not part of the coating solution. This could be attributed to residual powder presence in the coating chamber. The distribution of PVP among the sample surfaces depends on the concentration and the rate controlling polymer used. Differences can again be linked to polymer miscibility. Finally, it was shown that the underlying glass solution layer remains amorphous after coating of the rate controlling membrane, whether formed from an ethanol solution or an aqueous dispersion.


Assuntos
Preparações de Ação Retardada/química , Vidro/química , Indometacina/química , Membranas/química , Soluções Farmacêuticas/química , Cápsulas/química , Celulose/análogos & derivados , Celulose/química , Química Farmacêutica/métodos , Estudos Transversais , Excipientes/química , Polímeros/química , Pós/química , Solubilidade , Tecnologia Farmacêutica/métodos , Água/química
11.
AAPS PharmSciTech ; 18(4): 1009-1018, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27582072

RESUMO

In the present study, we report the properties of a mucoadhesive chitosan-pectinate nanoparticulate formulation able to retain its integrity in the milieu of the upper gastrointestinal tract and subsequently, mucoadhere and release curcumin in colon conditions. Using this system, we aimed to deliver curcumin to the colon for the possible management of colorectal cancer. The delivery system comprised of a chitosan-pectinate composite nanopolymeric with a z-average of 206.0 nm (±6.6 nm) and zeta potential of +32.8 mV (±0.5 mV) and encapsulation efficiency of 64%. The nanoparticles mucoadhesiveness was higher at alkaline pH compared to acidic pH. Furthermore, more than 80% release of curcumin was achieved in pectinase-enriched medium (pH 6.4) as opposed to negligible release in acidic and enzyme-restricted media at pH 6.8. SEM images of the nanoparticles after exposure to the various media indicate a retained matrix in acid media as opposed to a distorted/fragmented matrix in pectinase-enriched medium. The data strongly indicates that the system has the potential to be applied as a colon-targeted mucoadhesive curcumin delivery system for the possible treatment of colon cancer.


Assuntos
Quitosana , Neoplasias Colorretais/tratamento farmacológico , Curcumina , Sistemas de Liberação de Medicamentos , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Quitosana/química , Quitosana/farmacologia , Colo/efeitos dos fármacos , Curcumina/administração & dosagem , Curcumina/farmacocinética , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Humanos , Nanopartículas
12.
Anal Chem ; 88(7): 3481-7, 2016 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-26916467

RESUMO

The structure of a material, in particular the extremes of crystalline and amorphous forms, significantly impacts material performance in numerous sectors such as semiconductors, energy storage, and pharmaceutical products, which are investigated in this paper. To characterize the spatial distribution for crystalline-amorphous forms at the uppermost molecular surface layer, we performed time-of-flight secondary-ion mass spectroscopy (ToF-SIMS) measurements for quench-cooled amorphous and recrystallized samples of the drugs indomethacin, felodipine, and acetaminophen. Polarized light microscopy was used to localize crystallinity induced in the samples under controlled conditions. Principal component analysis was used to identify the subtle changes in the ToF-SIMS spectra indicative of the amorphous and crystalline forms for each drug. The indicators of amorphous and crystalline surfaces were common in type across the three drugs, and could be explained in general terms of crystal packing and intermolecular bonding, leading to intramolecular bond scission in the formation of secondary ions. Less intramolecular scission occurred in the amorphous form, resulting in a greater intensity of molecular and dimer secondary ions. To test the generality of amorphous-crystalline differentiation using ToF-SIMS, a different recrystallization method was investigated where acetaminophen single crystals were recrystallized from supersaturated solutions. The findings indicated that the ability to assign the crystalline/amorphous state of the sample using ToF-SIMS was insensitive to the recrystallization method. This demonstrates that ToF-SIMS is capable of detecting and mapping ordered crystalline and disordered amorphous molecular materials forms at micron spatial resolution in the uppermost surface of a material.


Assuntos
Acetaminofen/química , Felodipino/química , Indometacina/química , Espectrometria de Massa de Íon Secundário , Química Farmacêutica , Cristalização , Propriedades de Superfície , Fatores de Tempo
13.
Soft Matter ; 12(47): 9451-9457, 2016 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-27841428

RESUMO

Peptide-based biomaterials are key to the future of diagnostics and therapy, promoting applications such as tissue scaffolds and drug delivery vehicles. To realise the full potential of the peptide systems, control and optimisation of material properties are essential. Here we investigated the co-assembly of the minimal amyloid motif peptide, diphenylalanine (FF), and its tert-butoxycarbonyl (Boc)-modified derivative. Using Atomic Force Microscopy, we demonstrated that the co-assembled fibers are less rigid and show a curvier morphology. We propose that the Boc-modification of FF disrupts the hydrogen bond packing of adjacent N-termini, as supported by Fourier transform infrared and fluorescence spectroscopic data. Such rationally modified co-assemblies offer chemical functionality for after-assembly modification and controllable surface properties for tissue engineering scaffolds, along with tunable morphological vs. mechanical properties.

14.
Mol Pharm ; 12(9): 3389-98, 2015 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-26236939

RESUMO

The purpose of this study was to develop a predictive model of the amorphous stability of drugs with particular relevance for poorly water-soluble compounds. Twenty-five representative neutral poorly soluble compounds with a diverse range of physicochemical properties and chemical structures were systematically selected from an extensive library of marketed drug products. The physical stability of the amorphous form, measured over a 6 month period by the onset of crystallization of amorphous films prepared by melting and quench-cooling, was assessed using polarized light microscopy. The data were used as a response variable in a statistical model with calculated/predicted or measured molecular, thermodynamic, and kinetic parameters as explanatory variables. Several multiple linear regression models were derived, with varying balance between calculated/predicted and measured parameters. It was shown that inclusion of measured parameters significantly improves the predictive ability of the model. The best model demonstrated a prediction accuracy of 82% and included the following as parameters: melting and glass transition temperatures, enthalpy of fusion, configurational free energy, relaxation time, number of hydrogen bond donors, lipophilicity, and the ratio of carbon to heteroatoms. Good predictions were also obtained with a simpler model, which was comprised of easily acquired quantities: molecular weight and enthalpy of fusion. Statistical models are proposed to predict long-term amorphous drug stability. The models include readily accessible parameters, which are potentially the key factors influencing amorphous stability. The derived models can support faster decision making in drug formulation development.


Assuntos
Química Farmacêutica , Estabilidade de Medicamentos , Modelos Estatísticos , Preparações Farmacêuticas/química , Varredura Diferencial de Calorimetria , Ligação de Hidrogênio , Cinética , Solubilidade , Temperatura , Termodinâmica , Temperatura de Transição , Difração de Raios X
15.
J Microsc ; 258(2): 119-26, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25611705

RESUMO

Leaf surfaces are highly complex functional systems with well defined chemistry and structure dictating the barrier and transport properties of the leaf cuticle. It is a significant imaging challenge to analyse the very thin and often complex wax-like leaf cuticle morphology in their natural state. Scanning electron microscopy (SEM) and to a lesser extent Atomic force microscopy are techniques that have been used to study the leaf surface but their remains information that is difficult to obtain via these approaches. SEM is able to produce highly detailed and high-resolution images needed to study leaf structures at the submicron level. It typically operates in a vacuum or low pressure environment and as a consequence is generally unable to deal with the in situ analysis of dynamic surface events at submicron scales. Atomic force microscopy also possess the high-resolution imaging required and can follow dynamic events in ambient and liquid environments, but can over exaggerate small features and cannot image most leaf surfaces due to their inherent roughness at the micron scale. Scanning ion conductance microscopy (SICM), which operates in a liquid environment, provides a potential complementary analytical approach able to address these issues and which is yet to be explored for studying leaf surfaces. Here we illustrate the potential of SICM on various leaf surfaces and compare the data to SEM and atomic force microscopy images on the same samples. In achieving successful imaging we also show that SICM can be used to study the wetting of hydrophobic surfaces in situ. This has potentially wider implications than the study of leaves alone as surface wetting phenomena are important in a range of fundamental and applied studies.


Assuntos
Microscopia de Força Atômica/métodos , Microscopia Eletrônica de Varredura/métodos , Microscopia/métodos , Folhas de Planta/ultraestrutura , Microscopia/instrumentação , Microscopia de Força Atômica/instrumentação , Microscopia Eletrônica de Varredura/instrumentação
16.
Pharm Res ; 32(4): 1407-16, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25319105

RESUMO

PURPOSE: Miscibility of the different compounds that make up a solid dispersion based formulation play a crucial role in the drug release profile and physical stability of the solid dispersion as it defines the phase behaviour of the dispersion. The standard technique to obtain information on phase behaviour of a sample is (modulated) differential scanning calorimetry ((M)DSC). However, for ternary mixtures (M)DSC alone is not sufficient to characterize their phase behaviour and to gain insight into the distribution of the active pharmaceutical ingredient (API) in a two-phased polymeric matrix. METHODS: MDSC was combined with complementary surface analysis techniques, specifically time-of-flight secondary ion mass spectrometry (ToF-SIMS) and atomic force microscopy (AFM). Three spray-dried model formulations with varying API/PLGA/PVP ratios were analyzed. RESULTS: MDSC, TOF-SIMS and AFM provided insights into differences in drug distribution via the observed surface coverage for 3 differently composed ternary solid dispersions. CONCLUSIONS: Combining MDSC and surface analysis rendered additional insights in the composition of mixed phases in complex systems, like ternary solid dispersions.


Assuntos
Química Farmacêutica/métodos , Portadores de Fármacos/química , Inibidores da Protease de HIV/química , Ácido Láctico/química , Ácido Poliglicólico/química , Varredura Diferencial de Calorimetria , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Microesferas , Estrutura Molecular , Transição de Fase , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Solubilidade , Espectrometria de Massa de Íon Secundário , Propriedades de Superfície , Temperatura de Transição
17.
Mol Pharm ; 10(8): 3213-24, 2013 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-23844639

RESUMO

In view of the increasing interest in injectable controlled release formulations for the treatment of chronic diseases, injectable polymeric microspheres consisting of a surface layer of poly(lactic-co-glycolic acid) (PLGA) and an underlying polyvinylpyrrolidone (PVP) layer were previously developed. The present study focuses on the influence of heat and humidity on the surface characteristics of these spray-dried PLGA/PVP microspheres. The response of the polymeric matrix to these factors will provide an insight into the expected release behavior and stability of the formulation. This should result in the development of a drug matrix with desired and tunable characteristics in terms of physicochemical stability and drug release profile, relevant in a later stage of research. Glass transition temperatures (Tgs) and miscibility behavior were analyzed by modulated differential scanning calorimetry (MDSC). Scanning electron microscopy (SEM) provided insight in particle morphology. Atomic force microscopy (AFM) was used to study the nanoscale topography and phase behavior of the samples. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS) were utilized for surface chemical analysis and quantification respectively. It could be concluded that the surface characteristics (chemical composition, phase behavior, and topography) of spray-dried PVP/PLGA microparticles were affected by exposure to heat and humidity. When exposed to these conditions, a surface rearrangement occurs whereby an increase of PVP at the surface is observed, coupled with a decrease in PLGA. This phenomenon can be explained based upon the relative thermal characteristics and consequent molecular mobility of the two polymers.


Assuntos
Ácido Láctico/química , Microesferas , Ácido Poliglicólico/química , Polímeros/química , Povidona/química , Temperatura Alta , Umidade , Microscopia de Força Atômica , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
18.
Pharm Dev Technol ; 18(3): 591-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22149945

RESUMO

In the present study, we investigate the mucoadhesive characteristics and release of the anticancer agent curcumin, contained in chitosan nanoparticles (CS-NPs). Such a system has potential therapeutic benefits in the treatment of colon cancer through prolonged retention and delivery. The CS-NPs were ionically gelled with tripolyphosphate (TPP) and registered an isoelectric pH of 6.2 (z-average diameter of 214 nm ± 1.0 nm). pH variations around the isoelectric point caused a reduction in CS-NPs electrical charge which correspondingly increased the z-average due to agglomeration. Curcumin release from CS-NPs was slowest at chitosan to TPP weight ratio of 3:1, with a significant retention (36%) at the end of 6 h. Adsorption isotherms of mucin on CS-NPs fitted both the Freundlich and Langmuir models, suggesting a monolayer-limited adsorption on heterogeneous sites with varied affinities. Encapsulated curcumin exerted an influence on the adsorption of mucin due to H-bonding as well as π-π interactions between the phenolic moieties of curcumin and mucin.


Assuntos
Adesivos/síntese química , Quitosana/administração & dosagem , Colo , Curcumina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Adesivos/administração & dosagem , Animais , Quitosana/síntese química , Colo/efeitos dos fármacos , Curcumina/síntese química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/síntese química , Mucosa Intestinal/efeitos dos fármacos , Nanopartículas/administração & dosagem , Nanopartículas/química , Tamanho da Partícula , Suínos
19.
Zootaxa ; 3620: 89-111, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-26120698

RESUMO

Species of the anglerfish genus Chaunax Lowe, 1846 from the New Zealand region are taxonomically reviewed with six species recognized and described: Chaunax penicillatus McCulloch; C. nudiventer Ho & Shao, a new record for New Zealand; and four species new to science. Chaunax flavomaculatus sp. nov. distinguished by having its skin covered with a mix of numerous bifurcated and simple spinules, large yellow spots on dorsal surface of fresh specimens, and brownish coloured escal cirri; Chaunax mulleus sp. nov. by having a uniformly pink body with a deep red colour on ventral surfaces of the outer pectoral-fin and pelvic-fin, and lower part of caudal fin; Chaunax reticulatus sp. nov. by having cirri on the dorsal surface of head, and a pale reticulate colour pattern on a greyish background dorsally; and Chaunax russatus sp. nov. by its very wide illicial trough that is usually as wide or wider than the diameter of the pupil, and uniformly deep red body colour with creamy white to fuzzy greyish spots or patches on its dorsal surface. A key to species recognized from the study area is given.


Assuntos
Peixes/anatomia & histologia , Peixes/classificação , Animais , Nova Zelândia , Oceano Pacífico
20.
Zootaxa ; 3626: 188-200, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-26176132

RESUMO

Examination and taxonomic review of the batfishes collected from New Zealand and adjacent waters reveals five nominal species: Halieutopsis bathyoreos and Malthopsis mitrigera are recorded from New Zealand for the first time; the synonymy of Halieutaea maoria with H. stellata is confirmed, and two new species are described. Malthopsis asparata sp. nov. is unique in having stout principal bucklers with prominent spines. Malthopsis parva sp. nov. differs from congeners in having a naked abdomen, a short rostral spine directed upward, and all principal bucklers blunt.


Assuntos
Peixes/anatomia & histologia , Peixes/classificação , Animais , Nova Zelândia , Oceano Pacífico , Especificidade da Espécie
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