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1.
Biomacromolecules ; 17(9): 2830-8, 2016 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-27461341

RESUMO

Developing medical devices that resist bacterial attachment and subsequent biofilm formation is highly desirable. In this paper, we report the optimization of the molecular structure and thus material properties of a range of (meth)acrylate copolymers which contain monomers reported to deliver bacterial resistance to surfaces. This optimization allows such monomers to be employed within novel coatings to reduce bacterial attachment to silicone urinary catheters. We show that the flexibility of copolymers can be tuned to match that of the silicone catheter substrate, by copolymerizing these polymers with a lower Tg monomer such that it passes the flexing fatigue tests as coatings upon catheters, that the homopolymers failed. Furthermore, the Tg values of the copolymers are shown to be readily estimated by the Fox equation. The bacterial resistance performance of these copolymers were typically found to be better than the neat silicone or a commercial silver containing hydrogel surface, when the monomer feed contained only 25 v% of the "hit" monomer. The method of initiation (either photo or thermal) was shown not to affect the bacterial resistance of the copolymers. Optimized synthesis conditions to ensure that the correct copolymer composition and to prevent the onset of gelation are detailed.


Assuntos
Acrilatos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Aderência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana , Polímeros/farmacologia , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Substâncias Macromoleculares/química , Polimerização , Polímeros/química
2.
Nat Mater ; 13(6): 570-9, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24845996

RESUMO

Polymeric substrates are being identified that could permit translation of human pluripotent stem cells from laboratory-based research to industrial-scale biomedicine. Well-defined materials are required to allow cell banking and to provide the raw material for reproducible differentiation into lineages for large-scale drug-screening programs and clinical use. Yet more than 1 billion cells for each patient are needed to replace losses during heart attack, multiple sclerosis and diabetes. Producing this number of cells is challenging, and a rethink of the current predominant cell-derived substrates is needed to provide technology that can be scaled to meet the needs of millions of patients a year. In this Review, we consider the role of materials discovery, an emerging area of materials chemistry that is in large part driven by the challenges posed by biologists to materials scientists.


Assuntos
Materiais Biocompatíveis/química , Técnicas de Cultura de Células/métodos , Células-Tronco/citologia , Animais , Técnicas de Cultura de Células/instrumentação , Diabetes Mellitus/metabolismo , Diabetes Mellitus/terapia , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Esclerose Múltipla/metabolismo , Esclerose Múltipla/terapia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/terapia , Transplante de Células-Tronco , Células-Tronco/metabolismo
3.
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
4.
Proc Natl Acad Sci U S A ; 108(46): 18714-9, 2011 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-22065768

RESUMO

The current gold standard for the culture of human pluripotent stem cells requires the use of a feeder layer of cells. Here, we develop a spatially defined culture system based on UV/ozone radiation modification of typical cell culture plastics to define a favorable surface environment for human pluripotent stem cell culture. Chemical and geometrical optimization of the surfaces enables control of early cell aggregation from fully dissociated cells, as predicted from a numerical model of cell migration, and results in significant increases in cell growth of undifferentiated cells. These chemically defined xeno-free substrates generate more than three times the number of cells than feeder-containing substrates per surface area. Further, reprogramming and typical gene-targeting protocols can be readily performed on these engineered surfaces. These substrates provide an attractive cell culture platform for the production of clinically relevant factor-free reprogrammed cells from patient tissue samples and facilitate the definition of standardized scale-up friendly methods for disease modeling and cell therapeutic applications.


Assuntos
Técnicas de Cultura de Células , Células-Tronco Pluripotentes/citologia , Engenharia Tecidual/métodos , Materiais Biocompatíveis/química , Células Cultivadas , Humanos , Teste de Materiais , Microscopia de Fluorescência/métodos , Ozônio/química , Polímeros/química , Poliestirenos/química , Propriedades de Superfície , Transgenes , Raios Ultravioleta
5.
Chem Soc Rev ; 42(20): 7983-97, 2013 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-23857524

RESUMO

Small interfering ribonucleic acids (siRNAs) form potentially the most important class of next generation therapeutics. However, achieving their efficient delivery in the correct dose, time and location in the body remains a significant challenge. Rapid developments in the chemistries of siRNA formulations are enabling new strategies to overcome the core obstacles to delivery which include poor ribonuclease (RNase) resistance, short biological half-life, lack of tissue targeting, inefficient cellular uptake and undesirable toxicity. In this review we describe these principal challenges and evaluate recent approaches proposed to overcome the chemical, biochemical and physiological barriers. The role of the specific chemical structure of siRNA is considered and an overview of selected literature-reported siRNA formulations is provided. These include chemically-modified siRNAs and analogues, aptamer-siRNA chimeras, self-assembled nanoparticles, lipid and polymer complexes, bioconjugates and fusion protein complexes. We conclude the review with an outlook for the clinical use of this highly promising, but pharmaceutically challenging biotherapeutic.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanomedicina/métodos , RNA Interferente Pequeno/química , Animais , Pesquisa Biomédica , Humanos , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética
6.
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
7.
Phys Chem Chem Phys ; 15(38): 16263-74, 2013 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-23999994

RESUMO

New classes of information-rich DNA block co-polymer conjugates were synthesised, encoded with thermoresponsive and biocompatible poly(tri(ethylene glycol)ethyl ether methacrylate) (pTriEGMA) chains and oligomeric nucleic acids connected by either bioreducible or non-reducible links. The pTriEGMA chains were grown from initiator-functionalised hybridised DNA, designed to assemble with toehold overhangs. Functional information in the conjugates was explored via dynamic light scattering (DLS) and atomic force microscopy (AFM), in order to evaluate (i) reversible self-assembly into supramolecular structures across the pTriEGMA phase transition temperature; (ii) conformational change via addition of competing DNA sequences across the toeholds, and (iii) reductive cleavage of polymer-DNA links. The results showed that discrete nanoscale conjugates could reversibly associate through pTriEGMA phase behaviour and that size and association behaviour in one class of conjugate could be switched by addition of a competing DNA sequence and by reduction to break the polymer-DNA links. Preliminary experiments with the DNA-conjugates as delivery systems for doxorubicin to a cancer cell line indicated good tolerability of the conjugates alone and cytotoxic efficacy when loaded with the drug.


Assuntos
DNA/química , Polímeros/química , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/toxicidade , Materiais Biocompatíveis/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/toxicidade , Portadores de Fármacos/química , Humanos , Luz , Microscopia de Força Atômica , Hibridização de Ácido Nucleico , Transição de Fase , Espalhamento de Radiação , Temperatura de Transição
8.
Mol Pharm ; 9(1): 1-13, 2012 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22142438

RESUMO

The ability to deliver genetic material for therapy remains an unsolved challenge in medicine. Natural gene carriers, such as viruses, have evolved sophisticated mechanisms and modular biopolymer architectures to overcome these hurdles. Here we describe synthetic multicomponent materials for gene delivery, designed with features that mimic virus modular components and which transfect specific cell lines with high efficacy. The hierarchical nature of the synthetic carriers allows the incorporation of membrane-disrupting peptides, nucleic acid binding components, a protective coat layer, and an outer targeting ligand all in a single nanoparticle, but with functionality such that each is utilized in a specific sequence during the gene delivery process. The experimentally facile assembly suggests these materials could form a generic class of carrier systems that could be customized for many different therapeutic settings.


Assuntos
Materiais Biomiméticos/química , Proteínas do Capsídeo/química , Técnicas de Transferência de Genes , Nanopartículas/química , Neoplasias/metabolismo , Ácidos Nucleicos/química , Polímeros/química , Materiais Biomiméticos/efeitos adversos , Proteínas do Capsídeo/metabolismo , Endocitose , Óxido de Etileno/efeitos adversos , Óxido de Etileno/química , Técnicas de Transferência de Genes/efeitos adversos , Células HCT116 , Células HL-60 , Hemólise , Humanos , Ligantes , Nanopartículas/efeitos adversos , Nanopartículas/ultraestrutura , Proteínas de Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/terapia , Ácidos Nucleicos/metabolismo , Peptídeos/efeitos adversos , Peptídeos/química , Poliaminas/efeitos adversos , Poliaminas/química , Polieletrólitos , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/química , Polímeros/efeitos adversos , Receptores da Transferrina/metabolismo , Propriedades de Superfície , Transferrina/química , Transferrina/metabolismo
9.
Anal Chem ; 83(10): 3627-31, 2011 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-21495627

RESUMO

In recent years, there has been an increase in the use of time-of-flight secondary ion mass spectrometry (TOF-SIMS) for characterizing material surfaces. A great advantage of SIMS is that the analysis is direct and has excellent spatial resolution approaching a few hundred nanometers. However, the lack of the usual separation methods in mass spectrometry such as chromatography or ion mobility combined with the complexity of the heavily fragmented ions in the spectra means that the interpretation of multicomponent spectra in SIMS is very challenging indeed. The requirements for high-definition imaging, with say 256 × 256 pixels, in around 10 min analysis time places significant constraints on the instrument design so that separation using methods such as ion mobility with flight times of milliseconds are incompatible. Clearly, traditional liquid and gas chromatographies are not at all possible. Previously, we developed a method known as Gentle-SIMS (G-SIMS) that simplifies SIMS spectra so that the dominant ions are simply related to the structure of the substances analyzed. The method uses a measurement of the fragmentation behavior under two different primary ion source conditions and a control parameter known as the g-index. Here, we show that this method may be used "chromatographically" to separate the mass spectra of a drug molecule from the matrix polymer. The method may be used in real-time and is directly compatible with the majority of TOF-SIMS instruments. The applicability to other imaging mass spectrometeries is discussed.


Assuntos
Preparações Farmacêuticas/química , Polímeros/química , Espectrometria de Massa de Íon Secundário/métodos , Bupivacaína/química , Bupivacaína/isolamento & purificação , Codeína/química , Codeína/isolamento & purificação , Ácido Láctico/química , Preparações Farmacêuticas/isolamento & purificação , Poliésteres
10.
Nat Mater ; 9(9): 768-78, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20729850

RESUMO

Both human embryonic stem cells and induced pluripotent stem cells can self-renew indefinitely in culture; however, present methods to clonally grow them are inefficient and poorly defined for genetic manipulation and therapeutic purposes. Here we develop the first chemically defined, xeno-free, feeder-free synthetic substrates to support robust self-renewal of fully dissociated human embryonic stem and induced pluripotent stem cells. Material properties including wettability, surface topography, surface chemistry and indentation elastic modulus of all polymeric substrates were quantified using high-throughput methods to develop structure-function relationships between material properties and biological performance. These analyses show that optimal human embryonic stem cell substrates are generated from monomers with high acrylate content, have a moderate wettability and employ integrin alpha(v)beta(3) and alpha(v)beta(5) engagement with adsorbed vitronectin to promote colony formation. The structure-function methodology employed herein provides a general framework for the combinatorial development of synthetic substrates for stem cell culture.


Assuntos
Materiais Biocompatíveis/química , Técnicas de Química Combinatória/métodos , Células-Tronco Pluripotentes Induzidas/citologia , Diferenciação Celular , Células Cultivadas , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo
11.
Soft Matter ; 7(16): 7194-7197, 2011 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-23259005

RESUMO

Atomic force microscopy has been applied to an acrylate polymer microarray to achieve a full topographic characterisation. This process discovered a small number of hydro-responsive materials created from monomers with disparate hydrophilicities that show reversibility between pitted and protruding nanoscale topographies.

12.
Biomaterials ; 260: 120312, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32866726

RESUMO

Blood-contacting medical devices play an important role within healthcare and are required to be biocompatible, hemocompatible and resistant to microbial colonization. Here we describe a high throughput screen for copolymers with these specific properties. A series of weakly amphiphilic monomers are combinatorially polymerized with acrylate glycol monomers of varying chain lengths to create a library of 645 multi-functional candidate materials containing multiple chemical moieties that impart anti-biofilm, hemo- and immuno-compatible properties. These materials are screened in over 15,000 individual biological assays, targeting two bacterial species, one Gram negative (Pseudomonas aeruginosa) and one Gram positive (Staphylococcus aureus) commonly associated with central venous catheter infections, using 5 different measures of hemocompatibility and 6 measures of immunocompatibililty. Selected copolymers reduce platelet activation, platelet loss and leukocyte activation compared with the standard comparator PTFE as well as reducing bacterial biofilm formation in vitro by more than 82% compared with silicone. Poly(isobornyl acrylate-co-triethylene glycol methacrylate) (75:25) is identified as the optimal material across all these measures reducing P. aeruginosa biofilm formation by up to 86% in vivo in a murine foreign body infection model compared with uncoated silicone.


Assuntos
Antibacterianos , Infecções Estafilocócicas , Animais , Biofilmes , Camundongos , Pseudomonas aeruginosa , Staphylococcus aureus
13.
J Phys Chem B ; 113(34): 11574-82, 2009 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-19645457

RESUMO

In recent years, it has been demonstrated that cluster ion beams may be used to sputter some materials, particularly organic materials, without the significant accumulation of damage. It is therefore possible to use cluster ion beam sputtering in conjunction with a surface analytical technique, such as SIMS, to obtain depth profiles and three-dimensional images of the distribution of organic species in the near-surface region. For SIMS organic depth profiling to be useful as an analytical tool, it is important that it is able to measure physically meaningful quantities, such as the local concentration of a species within a blend. In this paper, we investigate a model system of a miscible binary mixture of codeine and poly(lactide). We show that there is a strong surface enrichment of poly(lactide), which provides a reference signal and permits the direct comparison of different samples in terms of secondary ion yield behavior. We demonstrate that it is possible to relate secondary ion intensities to local concentrations for a binary system and that there is a direct correspondence between the yield enhancement of one component and the yield suppression of the other. The dependence of secondary ion yield on composition is described using a model of the kinetically limited transfer of charge between secondary ions and secondary neutrals. Application of the model to pure materials under the assumption that only highly fragmented secondary ions are initially produced and interact with unfragmented secondary neutrals leads to the prediction that high molecular mass quasi-molecular ions have intensities proportional to the square of the total secondary ion yield. This relationship has been independently observed in other work (Seah, M. P. Surf. Interface Anal. 2007, 39, 634.).


Assuntos
Codeína/química , Poliésteres/química , Espectrometria de Massa de Íon Secundário/métodos , Cinética , Membranas Artificiais , Modelos Químicos , Propriedades de Superfície
14.
Biomaterials ; 29(2): 172-84, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17949809

RESUMO

This paper reports on the application of surface chemical gradients to study mammalian cell interactions with synthetic surfaces and investigates if the cell response on certain parts of the gradient is the same as that on uniform surfaces of equivalent chemistry. The gradients, formed using a diffusion-controlled plasma polymerisation technique, were fabricated such that cell response to a large range of different chemistries on a single sample could be investigated. Surface chemical gradients from hydrophobic plasma polymerised hexane (ppHex) to a more hydrophilic plasma polymerised allylamine (ppAAm), previously used to control cell density within 3D tissue-engineering scaffolds, were formed on glass coverslips. Surface characterisation was carried out to determine water contact angles (WCA), elemental composition, coating thickness and topography of the chemical gradients. Cell response was assessed following culture of 3T3 fibroblasts on both steep and shallow gradients. Fibroblasts adhered and proliferated preferentially on ppAAm (WCA approximately 60 degrees ) showing a gradual decreasing cell density towards the hydrophobic ppHex (WCA approximately 93 degrees ). Experiments on a uniform ppAAm surface revealed that there was a significant difference in cell density when compared to the gradient samples. The initial number of cells that adhered to the surface was confirmed as the difference between the uniform and graduated ppAAm samples, and it is assumed that this difference relates to different cell-cell signalling processes and/or greater protein production from surrounding cells on these two samples formats.


Assuntos
Polímeros/química , Engenharia Tecidual/instrumentação , Alilamina/química , Animais , Proliferação de Células , Hexanos/química , Camundongos , Microscopia de Força Atômica , Células NIH 3T3 , Análise Espectral , Propriedades de Superfície
15.
Adv Drug Deliv Rev ; 59(14): 1453-73, 2007 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-17920719

RESUMO

The scanning probe microscopes (SPMs) are a group of powerful surface sensitive instruments which when used complimentarily with traditional analytical techniques can provide invaluable, definitive information aiding our understanding and development of drug delivery systems. In this review, the main use of the SPMs (particularly the atomic force microscopy (AFM)) and their successes in forwarding drug delivery are highlighted and categorised into two interlinked sections namely, preformulation and formulation. SPM in preformulation concentrates on applications in pharmaceutical processes including, crystal morphology and modification, discriminating polymorphs, drug dissolution and release, solid state stability and interaction. The ability of the AFM to detect forces between different surfaces and at the same time to operate in liquids or controlled humidity and defined temperatures has also been particularly useful in the study of drug delivery. In formulation, the use of SPMs in different drug delivery systems is discussed in light of different host entry routes.


Assuntos
Química Farmacêutica/instrumentação , Sistemas de Liberação de Medicamentos , Microscopia de Varredura por Sonda/métodos , Animais , DNA/química , Estabilidade de Medicamentos , Excipientes , Humanos , Interpretação de Imagem Assistida por Computador , Microscopia de Força Atômica , Preparações Farmacêuticas/química , Receptores de Droga/química , Receptores de Droga/efeitos dos fármacos , Solubilidade
16.
J R Soc Interface ; 3(7): 277-81, 2006 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-16849237

RESUMO

Among the many biomolecules involved in the bone mineralization processes, anionic phospholipids play an important role because of their ability to bind calcium. In particular, phosphatidylserine is a natural component of the plasmalemma and of the matrix vesicles generated from the osteoblast membrane to create nucleation centres for calcium phosphate crystal precipitation. In the present work, we demonstrate that calcium-binding phospholipids can be used as biomimetic coating materials for improving the osteointegration of metal implants. Relatively thick phosphatidylserine-based coatings were deposited on titanium coupons by dip-coating. Upon dehydration in a simulated body fluid phospholipids were quickly crosslinked by calcium and re-arranged into a three-dimensional matrix able to induce rapid formation of a calcium phosphate mineral phase. The rate of mineralization was shown to be dependent on the adopted coating formulation. In the attempt to closely mimic the cell membrane composition, heterogeneous formulations based on the mixing of anionic phospholipids (either phosphatidylserine or phosphatidylinositol) with phosphatidylcholine and cholesterol were synthesized. However, surface plasmon resonance studies as well as scanning electron microscopy and elemental analysis demonstrated that the homogeneous phosphatidylserine coating was a more effective calcification environment than the heterogeneous formulations.


Assuntos
Materiais Biomiméticos/química , Fosfatos de Cálcio/química , Materiais Revestidos Biocompatíveis/química , Osseointegração/fisiologia , Fosfolipídeos/química , Próteses e Implantes , Materiais Biomiméticos/síntese química , Líquidos Corporais/química , Calcificação Fisiológica/fisiologia , Materiais Revestidos Biocompatíveis/síntese química , Simulação por Computador , Microscopia Eletrônica de Varredura , Ressonância de Plasmônio de Superfície
17.
Eur J Pharm Sci ; 28(4): 315-24, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16713199

RESUMO

The morphological, adhesion and surface energetic properties of three sulfathiazole polymorphs (III, IV and polymorph I prepared from both acetone and methanol, designated I-ace and I-met, respectively) produced using Nektar supercritical fluid (SCF) technology have been characterized using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Surface roughness values for each polymorph were determined at different length scales. At sample sizes less than 1micromx1microm the polymorphs rank in terms of roughness as follows: I-met>I-ace approximately equal to IV>III. At the larger scales the polymorphs rank in terms of roughness as follows: I-met>III>I-ace approximately equal to IV. The surface energies for polymorphs determined against graphite (HOPG) and particles of the same polymorph were, respectively, I-met: 0.99mJm(-2) (S.D. 1.25mJm(-2)), 3.09mJm(-2) (S.D. 2.67mJm(-2)); I-ace: 309mJm(-2) (S.D. 329mJm(-2)), 16mJm(-2) (S.D. 11mJm(-2)); III: 1.17mJm(-2) (S.D. 1.5mJm(-2)), 5.4mJm(-2) (S.D. 3.6mJm(-2)); IV: 20.35mJm(-2) (S.D. 28.5mJm(-2)), 16.8mJm(-2) (S.D. 9.6mJm(-2)). In terms of surface energies the polymorphs hence rank I-ace>IV>III approximately equal to I-met (HOPG adhesion measurements) and IV approximately equal to I-ace>III>I-met (particle cohesion measurements). Consideration of contacting asperities and surface roughness was shown to have limited effect on the surface energies, and instead the differences were ascribed to variations in the surface chemistry as a result of changes in crystallization mechanisms.


Assuntos
Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Sulfatiazóis/química , Acetona , Adesividade , Cromatografia com Fluido Supercrítico/métodos , Cristalização , Metanol , Solventes , Sulfatiazol , Propriedades de Superfície
18.
Eur J Pharm Sci ; 29(5): 405-13, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16978847

RESUMO

Using atomic force microscopy (AFM) the adhesion and sliding friction behaviour of single lactose particles attached directly to AFM cantilevers has been studied. Measurements were made on the two sides of a blister packaging material used in dry powder inhalers (DPI). Although no significant differences in adhesion were observed, clear differences in particle friction were evident, where one side offers consistently greater friction across the range of loads studied here. The packaging samples were characterised by time-of-flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS) and found to have different surface chemistries. The observed difference in friction behaviour is discussed in the context of the differences seen in surface chemistry, topography and hardness. It is reasoned that in this case hardness has the largest influence, and on one sample soft surface layers are displaced by the particle. A clear relationship between friction and load was only observed with one of the three particles tested; this was attributed to multiple asperities being brought into contact, illustrating the important role of nanoscale contact geometry in determining friction behaviour.


Assuntos
Embalagem de Medicamentos , Inaladores Dosimetrados , Pós , Fricção , Microscopia de Força Atômica , Propriedades de Superfície
19.
Int J Pharm ; 325(1-2): 163-71, 2006 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-16875789

RESUMO

Studies of single particle interactions in dry powder inhaler (DPI) formulations using atomic force microscopy (AFM) have recently grown in popularity. Currently, these experiments are all based on measuring particle adhesion forces. We broaden this approach by presenting a novel AFM friction study of single particles in a pharmaceutical system, to examine forces acting parallel to a surface. The sliding friction signal of lactose particles attached to AFM cantilevers was recorded in lateral force (LF) mode over 5 microm x 5 microm areas on five different surfaces chosen to represent both relevant inter-particle and particle-surface interactions. A ranking of friction forces was obtained as follows: glass approximately equal to zanamivir >zanamivir-magnesium stearate (99.5%/0.5%, w/w) blend approximately equal to magnesium stearate approximately equal to PTFE. The addition of magnesium stearate to the zanamivir surface dominated and significantly reduced the friction (Kruskal-Wallis test, P<0.001). AFM images of the contacting asperities of the lactose particles show changes in contact morphology due to two processes. Firstly the asperity wears flat due to abrasion and secondly small magnesium stearate particles transfer onto the asperity. It is proposed that in combination with AFM particle adhesion measurements, this method could be used to screen new formulations and the effectiveness of tertiary components in modifying carrier-drug interactions.


Assuntos
Nanotecnologia/métodos , Preparações Farmacêuticas/química , Combinação de Medicamentos , Estabilidade de Medicamentos , Fricção , Lactose/química , Microscopia de Força Atômica/instrumentação , Microscopia de Força Atômica/métodos , Tamanho da Partícula , Politetrafluoretileno/química , Ácidos Esteáricos/química , Propriedades de Superfície , Tecnologia Farmacêutica/métodos , Zanamivir/química
20.
Nucleic Acids Res ; 31(14): 4001-5, 2003 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-12853616

RESUMO

The need to protect DNA from in vivo degradation is one of the basic tenets of therapeutic gene delivery and a standard test for any proposed delivery vector. The currently employed in vitro tests, however, presently provide no direct link between the molecular structure of the vector complexes and their success in this role, thus hindering the rational design of successful gene delivery agents. Here we apply atomic force microscopy (AFM) in liquid to visualise at the molecular scale and in real time, the effect of DNase I on generation 4 polyamidoamine dendrimers (G4) complexed with DNA. These complexes are revealed to be dynamic in nature showing a degree of mobility, in some cases revealing the addition and loss of dendrimers to individual complexes. The formation of the G4-DNA complexes is observed to provide a degree of protection to the DNA. This protection is related to the structural morphology of the formed complex, which is itself shown to be dependent on the dendrimer loading and the time allowed for complex formation.


Assuntos
DNA/metabolismo , Desoxirribonuclease I/metabolismo , DNA/química , DNA/ultraestrutura , Substâncias Macromoleculares , Microscopia de Força Atômica/métodos , Poliaminas/química , Fatores de Tempo
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