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1.
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
2.
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
3.
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.

4.
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
5.
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
6.
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.

7.
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
8.
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.

9.
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
10.
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
11.
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
12.
PLoS One ; 12(9): e0182622, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28873097

RESUMO

Olive processing wastewaters (OPW), namely olive mill wastewater (OMW) and table-olive wastewaters (TOW) were evaluated for their antibacterial activity against five Gram-positive and two Gram-negative bacteria using the standard disc diffusion and thin layer chromatography (TLC)-bioautography assays. Disc diffusion screening and bioautography of OMW were compared to the phenolic extracts of table-olive brines. Positive activity against S. aureus was demonstrated. The optimization of chromatographic separation revealed that hexane/acetone in the ratio of 4:6 was the most effective for phenolic compounds separation. A HPLC-MS analysis was performed showing that only two compounds, hydroxytyrosol and tyrosol, were the predominant phenolic compounds in all OPW. The phenolic extract of OMW generated by a semi-modern process showed the highest free radical-scavenging activity (DPPH assay) compared to the other phenolic extracts. It is apparent from the present study that OPW are a rich source of antioxidants suitable for use in food, cosmetic or pharmaceutical applications.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Olea/química , Águas Residuárias/química , Compostos de Bifenilo/química , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Concentração Inibidora 50 , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Fenóis/química , Picratos/química , Staphylococcus aureus/efeitos dos fármacos
13.
Int J Pharm ; 526(1-2): 125-136, 2017 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-28461268

RESUMO

The highly effective barrier properties of the stratum corneum (SC) limit the application of transdermal delivery to relatively small, lipophilic molecules. Microneedles (MNs) however, offer a route to effectively deliver a wide range of pharmaceuticals through the skin, bypassing the SC in a non-invasive and pain-free manner. This study presents a dissolving MN system composed of polyvinylpyrrolidone (PVP) and trehalose to encapsulate active pharmaceutical peptides within the MN matrix. Rapid systemic delivery is then achieved once the needles have penetrated the SC and dissolved in the interstitial fluid of the skin. A variety of characterisation techniques were carried out to determine the optimum formulation. A model peptide, polymyxin B, was then incorporated into the MN system and delivered through porcine skin. In addition, the activity of the model drug was monitored during all stages of the formulation process.


Assuntos
Administração Cutânea , Sistemas de Liberação de Medicamentos , Microinjeções , Peptídeos/administração & dosagem , Animais , Química Farmacêutica , Agulhas , Pele , Suínos , Tecnologia Farmacêutica
14.
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
15.
Int J Pharm ; 494(1): 393-407, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26302859

RESUMO

Inhalation formulations are a popular way of treating the symptoms of respiratory diseases. The active pharmaceutical ingredient (API) is delivered directly to the site of action within the deep lung using an inhalation device such as the dry powder inhaler (DPI). The performance of the formulation and the efficiency of the treatment depend on a number of factors including the forces acting between the components. In DPI formulations these forces are dominated by interparticulate interactions. Research has shown that adhesive and cohesive forces depend on a number of particulate properties such as size, surface roughness, crystallinity, surface energetics and combinations of these. With traditional methods the impact of particulate properties on interparticulate forces could be evaluated by examining the bulk properties. Atomic force microscopy (AFM), however, enables the determination of local surface characteristics and the direct measurement of interparticulate forces using the colloidal probe technique. AFM is considered extremely useful for evaluating the surface topography of a substrate (an API or carrier particle) and even allows the identification of crystal faces, defects and polymorphs from high-resolution images. Additionally, information is given about local mechanical properties of the particles and changes in surface composition and energetics. The assessment of attractive forces between two bodies is possible by using colloidal probe AFM. This review article summarises the application of AFM in DPI formulations while specifically focussing on the colloidal probe technique and the evaluation of interparticulate forces.


Assuntos
Inaladores de Pó Seco , Microscopia de Força Atômica , Adesividade , Tamanho da Partícula , Pós , Propriedades de Superfície
16.
Int J Pharm ; 474(1-2): 25-32, 2014 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-25102115

RESUMO

Sevelamer hydrochloride is the first non-aluminium, non-calcium-based phosphate binder developed for the management of hyperphosphatemia in end stage renal diseases. It is a synthetic ion-exchange polymer which binds and removes phosphate ions due to the high content of cationic charge associated with protonated amine groups on the polymer matrix. This is the first in-depth study investigating phosphate removal in vitro from aqueous solutions using commercially available sevelamer hydrochloride at physiological conditions of phosphate level, pH and temperature. The kinetic and thermodynamic parameters of phosphate binding onto the sevelamer hydrochloride particles were evaluated in order to define the binding process. A series of kinetic studies were carried out in order to delineate the effect of initial phosphate concentration, absorbent dose and temperature on the rate of binding. The results were analysed using three kinetic models with the best-fit of the experimental data obtained using a pseudo-second order model. Thermodynamic parameters provide in-depth information on inherent energetic changes that are associated with binding. Free energy ΔG°, enthalpy ΔH°, and entropy ΔS° changes were calculated in this study in order to assess the relationship of these parameters to polymer morphology. The binding reaction was found to be a spontaneous endothermic process with increasing entropy at the solid-liquid interface.


Assuntos
Fosfatos/química , Poliaminas/química , Termodinâmica , Sítios de Ligação , Íons/química , Cinética , Sevelamer
17.
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
18.
PLoS One ; 9(2): e88599, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24586349

RESUMO

Forty eight individual pigs (8.7±0.26 kg) weaned at 28±1 d of age were used in a 22-d study to evaluate the effect of oral administration of a Bacillus pumilus spore suspension on growth performance and health indicators. Treatments (n = 16) were: (1) non-medicated diet; (2) medicated diet with apramycin (200 mg/kg) and pharmacological levels of zinc oxide (2,500 mg zinc/kg) and (3) B. pumilus diet (non-medicated diet + 10(10) spores/day B. pumilus). Final body weight and average daily gain tended to be lower (P = 0.07) and feed conversion ratio was worsened (P<0.05) for the medicated treatment compared to the B. pumilus treatment. Ileal E. coli counts were lower for the B. pumilus and medicated treatments compared to the non-medicated treatment (P<0.05), perhaps as a result of increased ileal propionic acid concentrations (P<0.001). However, the medicated treatment reduced fecal (P<0.001) and cecal (P<0.05) Lactobacillus counts and tended to reduce the total cecal short chain fatty acid (SCFA) concentration (P = 0.10). Liver weights were lighter and concentrations of liver enzymes higher (P<0.05) in pigs on the medicated treatment compared to those on the non-medicated or B. pumilus treatments. Pigs on the B. pumilus treatment had lower overall lymphocyte and higher granulocyte percentages (P<0.001) and higher numbers of jejunal goblet cells (P<0.01) than pigs on either of the other two treatments or the non-medicated treatment, respectively. However, histopathological examination of the small intestine, kidneys and liver revealed no abnormalities. Overall, the B. pumilus treatment decreased ileal E. coli counts in a manner similar to the medicated treatment but without the adverse effects on growth performance, Lactobacillus counts, cecal SCFA concentration and possible liver toxicity experienced with the medicated treatment.


Assuntos
Ração Animal , Bacillus , Biologia Marinha , Probióticos , Desmame , Animais , Escherichia coli/isolamento & purificação , Feminino , Concentração de Íons de Hidrogênio , Intestinos/microbiologia , Lactobacillus/isolamento & purificação , Masculino , Tamanho do Órgão , Suínos
19.
Int J Pharm ; 456(1): 10-20, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23958753

RESUMO

The objective of this study was to develop a novel antimicrobial seaweed wound dressing. The seaweed extract was active against nine clinically-relevant wound pathogens. A hydrogel formulation was prepared using polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP), followed by addition of 1% seaweed extract. The antimicrobial properties of the novel dressing were tested using agar diffusion assays, with release-profiles examined using gel leaching and gel transfer assays. The dressing was found to be effective against the same microbial strains as the seaweed extract, with similar efficacy to the commonly used silver-based dressing, Acticoat(®). Antimicrobial release-profile assays revealed that the dressing was effective in inhibiting 70-90% of the bacterial population within the first 30 min, followed by a long, sustained released up to 97 h, without leaving a residue following five subsequent transfers of the dressing. Antimicrobial activity was stable for up to 6 months of storage at 4 °C, but activity was reduced slightly after 15 weeks. Following autoclave sterilization, the dressing displayed a slower release profile compared to a non-autoclaved counterpart. Hence, the seaweed dressing may have commercial applications, potentially competing with silver-based dressings at a lower cost per-application. This is the first report of development of a seaweed-based antimicrobial dressing.


Assuntos
Anti-Infecciosos/farmacologia , Curativos Hidrocoloides , Extratos Vegetais/farmacologia , Rodófitas , Alga Marinha , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Álcool de Polivinil/química , Povidona/química , Cicatrização
20.
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
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