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1.
Pharm Res ; 33(7): 1638-48, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26964548

RESUMO

PURPOSE: Dexamethasone sodium phosphate (DXP) is an anti-inflammatory drug commonly used to treat acute and chronic ocular diseases. It is routinely delivered using eye-drops, where typically only 5% of the drug penetrates the corneal epithelium. The bioavailability of such ophthalmic drugs can be enhanced significantly using contact lenses incorporating drug-loaded nanoparticles (NPs). METHODS: The mechanism of release from chitosan NPs (CS-NPs), synthesized by ionic gelation, was studied in vitro. The DXP loaded CS-NPs were subsequently entrapped in contact lenses and the optical and drug-release properties were assessed. RESULTS: DXP release from CS-NPs followed diffusion and swelling controlled mechanisms, with an additional proposed impact from the electrostatic interaction between the drug and the CS-NPs. The release rate was found to increase with an increase in drug loading from 20 to 50 wt%. However, an inverse effect was observed when initial loading increased to 100 wt%. NP-laden lenses were optically clear (95-98% transmittance relative to the neat contact lens) and demonstrated sustained DXP release, with approximately 55.73% released in 22 days. CONCLUSIONS: The release profile indicated that drug levels were within the therapeutic requirement for anti-inflammatory use. These results suggest that these materials might be a promising candidate for the delivery of DXP and other important ophthalmic therapeutics.


Assuntos
Quitosana/química , Dexametasona/análogos & derivados , Metacrilatos/química , Nanopartículas/química , Polímeros/química , Lentes de Contato , Dexametasona/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Géis/química , Soluções Oftálmicas/química
2.
Mar Drugs ; 12(5): 2422-45, 2014 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-24796302

RESUMO

Six antimicrobial-producing seaweed-derived Bacillus strains were evaluated in vitro as animal probiotics, in comparison to two Bacillus from an EU-authorized animal probiotic product. Antimicrobial activity was demonstrated on solid media against porcine Salmonella and E. coli. The marine isolates were most active against the latter, had better activity than the commercial probiotics and Bacillus pumilus WIT 588 also reduced E. coli counts in broth. All of the marine Bacillus tolerated physiological concentrations of bile, with some as tolerant as one of the probiotics. Spore counts for all isolates remained almost constant during incubation in simulated gastric and ileum juices. All of the marine Bacillus grew anaerobically and the spores of all except one isolate germinated under anaerobic conditions. All were sensitive to a panel of antibiotics and none harbored Bacillus enterotoxin genes but all, except B. pumilus WIT 588, showed some degree of ß-hemolysis. However, trypan blue dye exclusion and xCELLigence assays demonstrated a lack of toxicity in comparison to two pathogens; in fact, the commercial probiotics appeared more cytotoxic than the majority of the marine Bacillus. Overall, some of the marine-derived Bacillus, in particular B. pumilus WIT 588, demonstrate potential for use as livestock probiotics.


Assuntos
Antibacterianos/farmacologia , Bacillus/fisiologia , Gado , Probióticos , Água do Mar/microbiologia , Microbiologia da Água , Anaerobiose , Animais , Antibacterianos/química , Bacillus/crescimento & desenvolvimento , Bactérias/efeitos dos fármacos , Bile/química , Adesão Celular/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Técnicas In Vitro , Testes de Sensibilidade Microbiana , Alga Marinha/microbiologia , Esporos Bacterianos/efeitos dos fármacos
3.
Int J Pharm ; 654: 123958, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38442797

RESUMO

Clinicians face numerous challenges when delivering medications to the eyes topically because of physiological barriers, that can inhibit the complete dose from getting to the intended location. Due to their small size, the ability to deliver drugs of different polarities simultaneously, and their biocompatibility, liposomes hold great promise for ocular drug delivery. This study aimed to develop and characterise a dual loaded liposome formulation encapsulating Bevacizumab (BEV) and Dexamethasone (DEX) that possessed the physicochemical attributes suitable for topical ocular delivery. Liposomes were prepared by using thin film hydration followed by extrusion, and the formulations were optimised using a design of experiments approach. Physicochemical characterisation along with cytocompatibility and bioactivity of the formulations were assessed. Liposomes were successfully prepared with a particle size of 139 ± 2 nm, PDI 0.03 ± 0.01 and zeta potential -2 ± 0.7 mV for the optimised formulation. BEV and DEX were successfully encapsulated into the liposomes with an encapsulation efficiency of 97 ± 0.5 % and 26 ± 0.5 %, respectively. A sustained release of BEV was observed from the liposomes and the bioactivity of the formulation was confirmed using a wound healing assay. In summary, a potential topical eye drop drug delivery system, which can co-load DEX and BEV was developed and characterised for its potential to be used in ocular drug delivery.


Assuntos
Sistemas de Liberação de Medicamentos , Lipossomos , Bevacizumab , Olho , Dexametasona , Tamanho da Partícula
4.
Eur J Pharm Biopharm ; 192: 62-78, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37797681

RESUMO

This study details the formation and characterisation of a novel nicotinamide adenine dinucleotide (NAD+)-associated polymeric nanoparticle system. The development of a polyelectrolyte complex (PEC) composed of two natural polyelectrolytes, hyaluronic acid and poly(L-lysine), and an evaluation of its suitability for NAD+ ocular delivery, primarily based on its physicochemical properties and in vitro release profile under physiological ocular flow rates, were of key focus. Following optimisation of formulation method conditions such as complexation pH, mode of addition, and charge ratio, the PEC was successfully formulated under mild formulation conditions via polyelectrolyte complexation. With a size of 235.1 ± 19.0 nm, a PDI value of 0.214 ± 0.140, and a zeta potential value of - 38.0 ± 1.1 mV, the chosen PEC, loaded with 430 µg of NAD+ per mg of PEC, exhibited non-Fickian, sustained release at physiological flowrates of 10.9 ± 0.2 mg of NAD+ over 14 h. PECs containing up to 200 µM of NAD+ did not induce any significant cytotoxic effects on an immortalised human corneal epithelial cell line. Using fluorescent labeling, the NAD+-associated PECs demonstrated retention within the corneal epithelium layer of a porcine model up to 6 h post incubation under physiological conditions. A study of the physicochemical behaviour of the PECs, in terms of size, zeta potential and NAD+ complexation in response to environmental stimuli,highlighted the dynamic nature of the PEC matrix and its dependence on both pH and ionic condition. Considering the successful formation of reproducible NAD+-associated PECs with suitable characteristics for ocular drug delivery via an inexpensive formulation method, they provide a promising platform for NAD+ ocular delivery with a strong potential to improve ocular health.


Assuntos
Ácido Hialurônico , NAD , Humanos , Animais , Suínos , Polieletrólitos/química , Polilisina , Sistemas de Liberação de Medicamentos
5.
Mar Drugs ; 10(10): 2280-2299, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23170084

RESUMO

The objectives of this study were (1) to assess the bacteriocinogenic potential of bacteria derived mainly from seaweed, but also sand and seawater, (2) to identify at least some of the bacteriocins produced, if any and (3) to determine if they are unique to the marine environment and/or novel. Fifteen Bacillus licheniformis or pumilus isolates with antimicrobial activity against at least one of the indicator bacteria used were recovered. Some, at least, of the antimicrobials produced were bacteriocins, as they were proteinaceous and the producers displayed immunity. Screening with PCR primers for known Bacillus bacteriocins revealed that three seaweed-derived Bacillus licheniformis harbored the bli04127 gene which encodes one of the peptides of the two-peptide lantibiotic lichenicidin. Production of both lichenicidin peptides was then confirmed by mass spectrometry. This is the first definitive proof of bacteriocin production by seaweed-derived bacteria. The authors acknowledge that the bacteriocin produced has previously been discovered and is not unique to the marine environment. However, the other marine isolates likely produce novel bacteriocins, as none harboured genes for known Bacillus bacteriocins.


Assuntos
Antibacterianos/metabolismo , Antibacterianos/farmacologia , Bacillus/classificação , Bacillus/metabolismo , Bacteriocinas/metabolismo , Bacteriocinas/farmacologia , Alga Marinha/microbiologia , Bacteriocinas/química , Técnicas Bacteriológicas , Meios de Cultura , Regulação Bacteriana da Expressão Gênica/fisiologia
6.
Arch Environ Contam Toxicol ; 63(1): 86-94, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22402781

RESUMO

Metal contamination is a common problem in aquatic environments and may result in metal bioaccumulation and toxicity in aquatic biota. Recent studies have reported the significance of dietary metal accumulation in aquatic food chains, particularly in species of lower trophic levels. This research investigated the accumulation and effects of dietary metals in a macroinvertebrate. The seaweed species Ulva lactuca and Enteromorpha prolifera were concurrently exposed to five metals (copper, nickel, lead, cadmium, and zinc) and then individually fed to the green sea urchin Strongylocentrotus droebachiensis for a period of 2 weeks. Body mass, test length, total length, and coelomic fluid ion concentration and osmolality were measured. The sea urchins were also dissected and their organs (esophagus, stomach, intestine, gonads, and rectum) digested and analyzed for metals. The results demonstrated that metal accumulation and distribution varied between seaweed species and among metals. In general, there were greater concentrations of metals within the sea urchins fed E. prolifera compared with those fed U. lactuca. All of the metals accumulated within at least one organ of S. droebachiensis, with Cu being most significant. These results indicate that E. prolifera may accumulate metals in a more bioavailable form than within U. lactuca, which could impact the grazer. In this study, no significant differences in body length, growth, or coelomic fluid ion concentration and osmolality were detected between the control and metal-exposed sea urchins after the 2-week testing period. This research presents new data concerning metal accumulation in a marine herbivore after dietary metal exposure.


Assuntos
Exposição Ambiental/análise , Metais Pesados/farmacocinética , Strongylocentrotus/metabolismo , Poluentes Químicos da Água/farmacocinética , Animais , Dieta , Cadeia Alimentar , Herbivoria/efeitos dos fármacos , Metais Pesados/toxicidade , Alga Marinha/química , Strongylocentrotus/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade
7.
Int J Pharm ; 621: 121793, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35526700

RESUMO

The naringenin (NAR)-impregnated hydrogel lenses (nesofilcon A material) were manufactured in this study with the feasibility to achieve controlled daily drug release. The lenses were fabricated using a comparable commercial-standard process, utilizing injection molding and thermal curing approaches. NAR-loaded lenses were prepared by both direct entrapment and 'soak and release' methods. Their critical properties were tested to ISO standards and comparable to the commercial lenses. NAR was fully characterized by studying its physical and chemical stability throughout the manufacturing processes using thermal analysis, high performance liquid chromatography and X-ray diffraction analysis. The NAR-loaded lenses showed > 97% light transmission, >75% water content, 0.50-0.53 ± 0.06 MPa tensile strength, with a lens diameter of 14.1 ± 0.1 mm. Lens polymerization kinetics were studied using differential scanning calorimetry. NAR released from the lens, prepared by a direct entrapment approach, followed a diffusion-controlled mechanism, and provided a controlled drug release of 72-82% for 24 h. A faster release rate was observed for NAR-loaded lenses prepared by a soak and release method, with over 90% of NAR was releasedin the first five hours.


Assuntos
Lentes de Contato Hidrofílicas , Flavanonas , Preparações de Ação Retardada , Hidrogel de Polietilenoglicol-Dimetacrilato , Hidrogéis/química
8.
Pharmaceutics ; 14(7)2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35890371

RESUMO

Extensive research is currently being conducted into novel ocular drug delivery systems (ODDS) that are capable of surpassing the limitations associated with conventional intraocular anterior and posterior segment treatments. Nanoformulations, including those synthesised from the natural, hydrophilic glycosaminoglycan, hyaluronic acid (HA), have gained significant traction due to their enhanced intraocular permeation, longer retention times, high physiological stability, inherent biocompatibility, and biodegradability. However, conventional nanoformulation preparation methods often require large volumes of organic solvent, chemical cross-linkers, and surfactants, which can pose significant toxicity risks. We present a comprehensive, critical review of the use of HA in the field of ophthalmology and ocular drug delivery, with a discussion of the physicochemical and biological properties of HA that render it a suitable excipient for drug delivery to both the anterior and posterior segments of the eye. The pivotal focus of this review is a discussion of the formation of HA-based nanoparticles via polyelectrolyte complexation, a mild method of preparation driven primarily by electrostatic interaction between opposing polyelectrolytes. To the best of our knowledge, despite the growing number of publications centred around the development of HA-based polyelectrolyte complexes (HA-PECs) for ocular drug delivery, no review articles have been published in this area. This review aims to bridge the identified gap in the literature by (1) reviewing recent advances in the area of HA-PECs for anterior and posterior ODD, (2) describing the mechanism and thermodynamics of polyelectrolyte complexation, and (3) critically evaluating the intrinsic and extrinsic formulation parameters that must be considered when designing HA-PECs for ocular application.

9.
Int J Pharm ; 621: 121806, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35526696

RESUMO

Sevelamer hydrochloride (SH) or Renagel® is an effective phosphate binder prescribed to prevent the absorption of phosphate in end stage renal disease (ESRD) patients. The relationship between SH structure and binding capacity and affinity is very important and can be used in characterising the sensitivity of the hydrogel to binding conditions. Thus, a series of hydrogels were prepared by varying the amount of crosslinker, whilst the other hydrogel components were kept constant. Variation of this parameter influenced the hydrogel structure as shown by swelling data, differential scanning calorimetry and solid state nuclear magnetic resonance spectroscopy. The hydrogels' physical characteristics were found to correlate with the number of phosphate binding sites and affinity obtained from the Langmuir-Freundlich Isotherm (L-FI) and affinity distribution spectra (AD). The hydrogels formed using lower amounts of crosslinker showed a slight increase in binding capacity but with lower affinity. However, the influence of the pH of the binding media on the binding parameters of sevelamer hydrochloride was significant. This is the first report on the use of AD spectra generated from L-FI binding parameters in hydrogels, which demonstrates the sensitivity of the affinity and binding site numbers to changes in hydrogel physical properties and the pH of the binding media.


Assuntos
Hidrogéis , Poliaminas , Humanos , Fosfatos/metabolismo , Poliaminas/química , Sevelamer
10.
Cont Lens Anterior Eye ; 44(6): 101487, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34353748

RESUMO

Therapeutic contact lenses for ocular drug delivery have received considerable interest as they can potentially enhance ocular bioavailability, increase patient compliance, and reduce side effects. Along with the successful in vitro and in vivo studies on sustained drug delivery through contact lenses, lens critical properties such as water content, optical transparency and modulus have also been investigated. Aside from issues such as drug stability or burst release, the potential for the commercialization of pharmaceutical-loaded lenses can be limited by the alteration of lens physical and chemical properties upon the incorporation of therapeutic or non-therapeutic components. This review outlines advances in the use of pharmaceutical-loaded contact lenses and their relevant characterization methodologies as a potential ocular drug delivery system from 2010 to 2020, while summarizing current gaps and challenges in this field. A key reference point for this review is the relevant ISO standards on contact lenses, relating to the associated characterization methodologies. The content of this review is categorized based on the chemical, physical and mechanical properties of the loaded lens with the shortcomings of such analytical technologies examined.


Assuntos
Lentes de Contato Hidrofílicas , Cristalino , Preparações Farmacêuticas , Sistemas de Liberação de Medicamentos , Olho , Humanos
11.
Pharmaceutics ; 13(10)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34683883

RESUMO

The current treatment for the acquired retinal vasculopathies involves lifelong repeated intravitreal injections of either anti-vascular endothelial growth factor (VEGF) therapy or modulation of inflammation with steroids. Consequently, any treatment modification that decreases this treatment burden for patients and doctors alike would be a welcome intervention. To that end, this research aims to develop a topically applied nanoparticulate system encapsulating a corticosteroid for extended drug release. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) supports the controlled release of the encapsulated drug, while surface modification of these NPs with chitosan might prolong the mucoadhesion ability leading to improved bioavailability of the drug. Triamcinolone acetonide (TA)-loaded chitosan-coated PLGA NPs were fabricated using the oil-in-water emulsion technique. The optimized surface-modified NPs obtained using Box-Behnken response surface statistical design were reproducible with a particle diameter of 334 ± 67.95 to 386 ± 15.14 nm and PDI between 0.09 and 0.15. These NPs encapsulated 55-57% of TA and displayed a controlled release of the drug reaching a plateau in 27 h. Fourier-transform infrared spectroscopic (FTIR) analysis demonstrated characteristic peaks for chitosan (C-H, CONH2 and C-O at 2935, 1631 and 1087 cm-1, respectively) in chitosan-coated PLGA NPs. This result data, coupled with positive zeta potential values (ranged between +26 and +33 mV), suggests the successful coating of chitosan onto PLGA NPs. Upon coating of the NPs, the thermal stability of the drug, polymer, surfactant and PLGA NPs have been enhanced. The characteristics of the surface-modified NPs supports their use as potential candidates for topical ocular drug delivery for acquired retinal vasculopathies.

12.
Pharmaceutics ; 13(6)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207223

RESUMO

Dry eye disease (DED) or keratoconjunctivitis sicca is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction. Symptoms include dryness, irritation, discomfort and visual disturbance, and standard treatment includes the use of lubricants and topical steroids. Secondary inflammation plays a prominent role in the development and propagation of this debilitating condition. To address this we have investigated the pilot scale development of an innovative drug delivery system using a dexamethasone-encapsulated cholesterol-Labrafac™ lipophile nanostructured lipid carrier (NLC)-based ophthalmic formulation, which could be developed as an eye drop to treat DED and any associated acute exacerbations. After rapid screening of a range of laboratory scale pre-formulations, the chosen formulation was prepared at pilot scale with a particle size of 19.51 ± 0.5 nm, an encapsulation efficiency of 99.6 ± 0.5%, a PDI of 0.08, and an extended stability of 6 months at 4 °C. This potential ophthalmic formulation was observed to have high tolerability and internalization capacity for human corneal epithelial cells, with similar behavior demonstrated on ex vivo porcine cornea studies, suggesting suitable distribution on the ocular surface. Further, ELISA was used to study the impact of the pilot scale formulation on a range of inflammatory biomarkers. The most successful dexamethasone-loaded NLC showed a 5-fold reduction of TNF-α production over dexamethasone solution alone, with comparable results for MMP-9 and IL-6. The ease of formulation, scalability, performance and biomarker assays suggest that this NLC formulation could be a viable option for the topical treatment of DED.

13.
Mar Drugs ; 8(7): 2038-64, 2010 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-20714423

RESUMO

The marine environment is an untapped source of bioactive compounds. Specifically, marine macroalgae (seaweeds) are rich in polysaccharides that could potentially be exploited as prebiotic functional ingredients for both human and animal health applications. Prebiotics are non-digestible, selectively fermented compounds that stimulate the growth and/or activity of beneficial gut microbiota which, in turn, confer health benefits on the host. This review will introduce the concept and potential applications of prebiotics, followed by an outline of the chemistry of seaweed polysaccharides. Their potential for use as prebiotics for both humans and animals will be highlighted by reviewing data from both in vitro and in vivo studies conducted to date.


Assuntos
Polissacarídeos/química , Prebióticos , Alga Marinha/química , Animais , Fermentação , Trato Gastrointestinal/microbiologia , Humanos , Polissacarídeos/isolamento & purificação
14.
Int J Pharm ; 366(1-2): 190-200, 2009 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-18812218

RESUMO

The development of novel cutaneous delivery technologies that can produce micron-sized channels within the outermost skin layers has stimulated interest in the skin as an interface for localised and systemic delivery of macromolecular and nanoparticulate therapeutics. This investigation assesses the contribution of physicochemical factors to the rate and extent of nanoparticle delivery through microchannels created in a biological tissue, the skin, by novel delivery technologies such as the microneedle array. The hydrodynamic diameter, zeta potential and surface morphology of a representative fluorescent nanoparticle formulation were characterised. Permeation studies using static Franz-type diffusion cells assessed (i) the diffusion of nanoparticle formulations through a model membrane containing uniform cylindrical microchannels of variable diameter and (ii) nanoparticle penetration across microneedle treated human skin. Wet-etch microneedle array devices can be used to significantly enhance the intra/transdermal delivery of nanoparticle formulations. However the physicochemical factors, microchannel size and particle surface charge, have a significant influence on the permeation and subsequent distribution of a nanoparticle formulation within the skin. Further work is required to understand the behaviour of nanoparticle formulations within the biological environment and their interaction with the skin layers following disruption of the skin barrier with novel delivery devices such as the microneedle array.


Assuntos
Microinjeções/métodos , Nanopartículas , Preparações Farmacêuticas/administração & dosagem , Pele/metabolismo , Idoso , Difusão , Feminino , Fluorescência , Humanos , Microinjeções/instrumentação , Agulhas , Permeabilidade , Absorção Cutânea
15.
Sci Rep ; 9(1): 17911, 2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784603

RESUMO

Antimicrobial resistant strains of infection are afflicting clinical settings, driving the search for novel antimicrobial compounds. Naturally sourced bioactives, for instance those from seaweeds, have the potential to ameliorate this issue. As such, solvent extracts from the edible Irish seaweeds Fucus serratus and Fucus vesiculosus were screened for antimicrobial activity against 28 clinically isolated strains of MRSA, including one GISA (glycopeptide intermediate S. aureus) and two mecC gene containing strains. The water extract of F. vesiculosus was the most promising extract went on to be tested for biofilm prevention and disruption activity. The disk diffusion method was used to investigate the inhibition of the bacterial pathogens tested while MIC, MBC and biofilm disruption and prevention analyses were performed spectroscopically and by plate counts, respectively. Solvent extracts were found to have a wide array of antimicrobial activity against the strains tested, with the water extract from Fucus vesiculosus being the most promising. This extract was also found to both prevent and disrupt MRSA biofilms indicating the potential extract as new antimicrobials, and raising the possibility of their possible use in therapeutics.


Assuntos
Antibacterianos/farmacologia , Fucus/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Extratos Vegetais/farmacologia , Antibacterianos/toxicidade , Biofilmes/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/fisiologia , Extratos Vegetais/toxicidade
16.
Int J Pharm ; 565: 9-19, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31047995

RESUMO

Microneedle technology offers a viable means of delivering biologically active pharmaceutical agents across the skin in a minimally invasive and virtually pain free manner. Previous work detailed the first successful transdermal delivery of a model peptide drug, polymyxin b, utilising a dissolving polymer-based microneedle system. The focus of this study was to examine the ability of a dissolving microneedle system to deliver a range of peptides of different sizes and properties. Analogue versions of 2 existing therapeutic peptides; pentagastrin and sincalide, were synthesised utilising Fmoc based solid phase peptide synthesis (SPPS) chemistry techniques and once successfully synthesised and purified, the peptide analogues were characterised using LC-MS. The peptide analogues were then incorporated into PVP/trehalose microneedle formulations. Skin permeation testing, in addition to skin penetration testing, was carried out to determine the effectiveness of the microneedle system to deliver the peptide analogues through porcine skin. The results obtained from these studies were then compared with the permeation results obtained utilising polymyxin B as the peptide drug cargo to evaluate the PVP/trehalose microneedle system's suitability to successfully deliver therapeutic peptides. Results indicated that the microneedle system successfully systemically delivered a higher overall percentage of the encapsulated peptides at an initially faster rate than peptide loaded control discs and in therapeutically relevant concentrations.


Assuntos
Sistemas de Liberação de Medicamentos , Agulhas , Pentagastrina/administração & dosagem , Sincalida/administração & dosagem , Administração Cutânea , Animais , Feminino , Masculino , Microinjeções , Polimixina B/administração & dosagem , Pele/metabolismo , Absorção Cutânea , Solubilidade , Suínos
17.
BMJ Support Palliat Care ; 9(4): e28, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27075983

RESUMO

BACKGROUND: Key Information Summaries (KIS) were introduced throughout Scotland in 2013 so that anticipatory care plans written by general practitioners (GPs) could be routinely shared electronically and updated in real time, between GPs and providers of unscheduled and secondary care. AIMS: We aimed to describe the current reach of anticipatory and palliative care, and to explore GPs' views on using KIS. METHODS: We studied the primary care records of all patients who died in 2014 in 9 diverse Lothian practices. We identified if anticipatory or palliative care had been started, and if so how many weeks before death and which aspects of care had been documented. We interviewed 10 GPs to understand barriers and facilitating factors. RESULTS: Overall, 60% of patients were identified for a KIS, a median of 18 weeks before death. The numbers identified were highest for patients with cancer, with 75% identified compared with 66% of those dying with dementia/frailty and only 41% dying from organ failure. Patients were more likely to die outside hospital if they had a KIS. GPs identified professional, patient and societal challenges in identifying patients for palliative care, especially those with non-cancer diagnoses. CONCLUSIONS: GPs are identifying patients for anticipatory and palliative care more equitably across the different disease trajectories and earlier in the disease process than they were previously identifying patients specifically for palliative care. However, many patients still lack care planning, particularly those dying with organ failure.


Assuntos
Clínicos Gerais/estatística & dados numéricos , Cuidados Paliativos/estatística & dados numéricos , Planejamento de Assistência ao Paciente/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Assistência Terminal/estatística & dados numéricos , Adulto , Idoso , Demência/terapia , Feminino , Clínicos Gerais/psicologia , Humanos , Disseminação de Informação , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Cuidados Paliativos/psicologia , Escócia
18.
Anal Bioanal Chem ; 391(4): 1237-44, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18345531

RESUMO

A novel thermal desorption technique using a direct-probe device (Chromatoprobe) attached to a gas chromatograph-mass spectrometer is presented for the thermal pretreatment, characterisation and analysis of molecularly imprinted polymers. The technique is demonstrated as effective for the removal of volatile materials, including template and unreacted monomers, from methacrylic acid-ethylene glycol dimethacrylate copolymers imprinted with 2-aminopyridine. Mass spectrometry is a powerful technique for polymer bleed characterisation. Thermal desorption studies on reloaded template and related compounds are reported as a means of assessing polymer morphology, specific binding by imprinted polymers compared with reference non-imprinted polymers and selective binding by an imprinted polymer for its template. Calibration studies on the thermal desorption technique using an internal standard are presented with R(2) > 0.999. The technique provides a novel method for assessment of polymer thermal stability, composition and morphology.

19.
Anal Bioanal Chem ; 391(4): 1245-53, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18408922

RESUMO

A powerful method utilising direct probe thermal desorption GC-MS is presented for the study of molecularly imprinted polymers (MIPs). A series of 2-aminopyridine (2-apy)-imprinted methacrylic acid-ethyleneglycol dimethacrylate (MAA-EGDMA) copolymers were prepared under identical conditions but with varying amounts of EGDMA (crosslinking monomer). The use of appropriate temperature programmes permitted template removal, and the subsequent assessment of polymer affinity and specificity, all of which were found to be dependent on polymer composition and morphology. The system was sufficiently sensitive to identify a specific response of imprinted polymers over nonimprinted counterparts. Correlations were found to exist between thermal desorption analysis and solution phase binding, which was assessed by UV spectroscopy, where specificity was found to diminish with decreasing EGDMA concentration. This was attributed to the increased number of free carboxyl groups in those polymers containing a lower percentage of EGDMA. Thermal desorption profiles obtained for the analyte were found to be unaffected by the physical and chemical properties of the solvent used for analyte reloading.


Assuntos
Reagentes de Ligações Cruzadas/análise , Reagentes de Ligações Cruzadas/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Impressão Molecular/métodos , Polímeros/análise , Polímeros/química , Temperatura , Nitrogênio/química , Porosidade , Sensibilidade e Especificidade , Soluções , Solventes
20.
Anal Bioanal Chem ; 391(4): 1229-36, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18246331

RESUMO

A detailed investigation into the functional groups responsible for the formation of a noncovalent complex between 2-aminopyridine (template) and methacrylic acid (functional monomer) has been carried out using FTIR spectroscopy and confirmed by (1)H NMR spectroscopic data. The approach adopted to confirm the mechanism of interaction was the analysis of the template plus the structurally similar 2-methylaminopyridine and 2-dimethylaminopyridine. A 1:1 stoichiometry of complexation was determined by Job plot analysis following titration, with FTIR results complementing those of the (1)H NMR study. The strength of interaction between 2-aminopyridine and the functional monomer measured through band shifts by FTIR spectroscopy was compared with such interactions for the isomers 3- and 4-aminopyridine. This comparison identified a clear correlation between template pK(a), degree of interaction and subsequent nonspecific binding in the nonimprinted polymer. Using FTIR spectroscopy it was also possible to observe the effect of temperature on the prepolymerisation solution. IR spectra showed that lower temperatures led to more stabilized interactions of the hydrogen-bonded complex. The potential advantages of FTIR spectroscopy compared with (1)H NMR spectroscopy in studying prepolymerisation solutions have been identified.


Assuntos
Compostos Heterocíclicos/análise , Compostos Heterocíclicos/química , Espectroscopia de Ressonância Magnética/métodos , Nitrogênio/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Aminopiridinas/química , Metacrilatos/química , Estrutura Molecular
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