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1.
Eur J Pharm Biopharm ; 154: 270-282, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32717386

RESUMO

This study reports the use of ITC in understanding the thermodynamics occurring for a controlled release system in which complexation has been exploited. In this study, a model drug, propranolol hydrochloride (PPN) was complexed with magnesium aluminium silicate (MAS) and these complexes were used in combination with polyethylene oxide (PEO) as a hydrophilic carrier at various concentrations to sustain the release of PPN. DSC, XRPD, ATR-FTIR and SEM/EDX were successfully used in characterising the produced complexes. 2D- SAXS data patterns for MAS and the produced complexes were shown to be symmetric and circular with the particles showing no preferred orientation at the nanometre scale. ITC studies showed differences between PPN adsorption onto MAS compared with PPN adsorption onto a MAS-PEO mixture. At both temperatures studied the binding affinity Ka was greater for the titration of PPN into the MAS-PEO mixture (5.37E + 04 ± 7.54E + 03 M at 25 °C and 8.63E + 04 ± 6.11E + 03 M at 37 °C), compared to the affinity obtained upon binding between PPN and MAS as previously reported suggesting a stronger binding with implications for the dissolution process. MAS-PPN complexes with the PEO polymer compacts displayed desired manufacturing and formulation properties for a formulator including, reduced plastic recovery therefore potentially reducing the risk of cracking/splitting and on tooling wear, controlled release of PPN at a significantly low (5%) polymer level as well as a zero-order release profile (case II transport) using up to 50% polymer level.


Assuntos
Compostos de Alumínio/análise , Liberação Controlada de Fármacos , Compostos de Magnésio/análise , Nanocompostos/análise , Polímeros/análise , Espalhamento a Baixo Ângulo , Silicatos/análise , Compostos de Alumínio/metabolismo , Compostos de Magnésio/metabolismo , Polímeros/metabolismo , Silicatos/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
2.
Eur J Pharm Biopharm ; 154: 1-7, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32599271

RESUMO

Poorly soluble drugs are often unsuitable to incorporate in ocular in situ gelling systems due to the aqueous based gelling formulations and low volumes administered. For such formulations to be successful, the administered drug must have sufficient solubility to diffuse from the formulation to the eye and should not affect the gelation of the in situ gelling material. Drug salt forms can improve the solubility of poorly soluble drugs, however, as in situ gel forming formulations are often designed to be crosslinked by salts (present the lacrimal fluid) it can make salt forms difficult to formulate. The aim of this study was to develop an in situ gel forming ophthalmic formulation of a poorly soluble drug flurbiprofen (FBP) through cyclodextrin complex formation and to analyse the impact on gelation, release and permeation through the cornea. Hydroxypropyl-beta-cyclodextrin (HßCD) was used as a complexing agent and low acyl gellan gum was added to the FBP- HßCD complex as a water soluble in situ gelling polymer. Measurements were performed using rheo-dissolution, which utilises a rheometer with a modified lower plate that has the unique ability to allow rheological measurement and analysis of drug release simultaneously. An ex-vivo permeation study was also performed using porcine cornea. Rheological measurements in terms of elastic (G') and viscous (G″) modulus showed rapid gelation of the formulation upon contact with simulated lacrimal fluid (SLF). Approximately, 97% FBP was released when 10% HßCD was used and release was decreased to 79% when the amount of HßCD was increased to 20%. The percentage of drug permeation through the cornea was 55% in 300 min whereas the marketed non gelling eye drop formulation containing FBP sodium showed only 37% permeation. The data presented here, revealed that not only could a poorly soluble drug be complexed with cyclodextrin and loaded into an in situ gelling system without interfering with the gelation, but also permeability the of the drug improved.


Assuntos
Sistemas de Liberação de Medicamentos/normas , Géis/administração & dosagem , Géis/metabolismo , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/metabolismo , Água/metabolismo , Animais , Córnea/efeitos dos fármacos , Córnea/metabolismo , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Liberação Controlada de Fármacos/fisiologia , Permeabilidade/efeitos dos fármacos , Polissacarídeos Bacterianos/administração & dosagem , Polissacarídeos Bacterianos/metabolismo , Reologia/métodos , Reologia/normas , Solubilidade/efeitos dos fármacos , Suínos
3.
Colloids Surf B Biointerfaces ; 188: 110809, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31972440

RESUMO

This study was aimed at investigating the effect of grewia polysaccharides on the mechanical and release properties of tablet matrices containing binary mixtures of the polysaccharide with psyllium. Two grades of grewia polysaccharides (GG and GDS) were extracted and binary mixtures of the polysaccharides with psyllium were formulated into tablet matrices containing theophylline as the model drug. The true, bulk and tapped densities, Carr's compressibility index of the powders and binary composites were determined before tablet compression. Tablet properties (hardness, porosity, and drug release from the matrices) were investigated. The dissolution test was carried out in 0.1 M HCl (pH 1.2) and phosphate buffer (pH 6.8). The results show that GG and GDS produced tablets with good mechanical strength (108.33 N and 95.70 N, respectively) while psyllium produced softer tablets (7.13 N). The combination of psyllium and grewia polysaccharides in the matrices resulted in a significant increase in the mechanical strength of the matrices when compared to matrices containing psyllium alone as the matrix former. The results also showed that GG and GDS reduced the dissolution rate and effectively eliminated the burst release of theophylline from the psyllium matrices at both pHs. The matrices of GG or GDS and the binary mixtures conform to non-Fickian anomalous diffusion with n > 0.45. When overcoming the burst release of drug from matrices such as psyllium, grewia polysaccharides may provide an effective reduction and a more sustained drug release from such matrices.


Assuntos
Grewia/química , Polissacarídeos/química , Psyllium/química , Teofilina/química , Liberação Controlada de Fármacos , Tamanho da Partícula , Pós/química , Estresse Mecânico , Propriedades de Superfície , Comprimidos/química
4.
Sci Rep ; 10(1): 577, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953500

RESUMO

The present study aimed to explore a new source of montmorillonite and to develop an extraction and purification protocol for its isolation from raw clay samples acquired from the Koh-e-Suleiman mountain range in Pakistan. The process involved the collection of raw clay from the source, identification and quantification of montmorillonite. Granulometric extraction and purification protocols increased the montmorillonite content from 21.8-25.1% in the raw clay to 90.1-93.9% after small-scale extraction and 85.33-89.33% on a larger scale. A techno-economic analysis highlighted the practicality and economic benefits of large-scale extraction for industrial applications. This study highlights the existence of a substantial new source of this valuable clay which is currently used across multiple industries including construction, pottery making, pharmaceuticals, cosmetics and engineering. It is intuitively expected that the large-scale extraction of the material will improve the economic condition of the region by providing employment opportunities to locals and may be a valuable resource for export.

5.
Carbohydr Polym ; 229: 115541, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31826516

RESUMO

There is great potential to improve drug delivery through the use of in-situ gelling delivery systems. Here we demonstrate a technique capable of measuring changes in rheology (gelation and/or dissolution) of in-situ gelling delivery systems on contact with physiological fluid, while simultaneously analysing drug release. An ocular in-situ gelling formulation (gellan and timolol maleate) and an in-situ gelling oral liquid (alginate and metronidazole) were used as exemplar formulations. The method allowed profiling of increasing gellan concentration resulting in a reduction of timolol maleate released into simulated lacrimal fluid. When alginate was used as an in-situ gelling oral formulation there was a rapid increase in G' on contact with simulated gastric fluid. When this was changed to simulated intestinal fluid, drug release rate increased rapidly, coinciding with alginate gel dissolution. This work highlights the potential of this technology as a tool in development and optimisation of these increasingly popular delivery systems.


Assuntos
Portadores de Fármacos/química , Géis/química , Metronidazol/química , Timolol/química , Alginatos/química , Química Farmacêutica , Liberação Controlada de Fármacos , Metronidazol/metabolismo , Soluções Oftálmicas/química , Soluções Oftálmicas/metabolismo , Polissacarídeos Bacterianos/química , Reologia , Timolol/metabolismo , Viscosidade
6.
Int J Pharm X ; 1: 100003, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31545854

RESUMO

Isothermal titration calorimetry (ITC) along with attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDX) and high-performance liquid chromatography (HPLC) were employed to investigate the process of adsorption of propranolol hydrochloride (PPN) onto magnesium aluminium silicate (MAS) and to characterise the MAS-PPN particles formed upon complexation. The composition of MAS was confirmed by infrared (IR) spectroscopy and a calcimeter. The calorimetric results confirmed the binding between PPN and MAS at various pHs and temperatures. The overall change in enthalpy was found to be exothermic with a comparatively small entropic contribution to the total change in Gibbs free energy. These findings suggest that the binding process was enthalpically driven and entropically unfavourable (lower affinity) suggesting hydrogen bonding and electrostatic interactions dominating the interaction. The variation of pH and temperature did not have a great impact on the thermodynamics of the binding process, as observed from the similarity in enthalpy (ΔH), entropy (ΔS) or Gibbs free energy (ΔG). A slight reduction in the binding affinity (Ka) with varing pH and temperature was however observed. SEM/EDX studies showed the occurrence of changes in the microstructural properties of MAS following complexation which may explain the potential of MAS-PPN complexes for controlled drug release promoting pharmaceutical innovation.

7.
Drug Dev Ind Pharm ; 44(2): 251-260, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29057675

RESUMO

Concomitant ingestion of alcohol and medications can greatly affect drug plasma concentrations as dose dumping or failure may occur as a result of the fact that formulation excipients may not always be resistant to alcohol. In this study, a natural polysaccharide (Sesamum radiatum gum) (SG) was extracted, characterized and used to formulate sustained release theophylline compacts to study the effect of varying alcohol concentrations (v/v) in dissolution media on drug release from these compacts. X-ray powder diffraction showed that the extracted gum was amorphous in nature with the powder having excellent compaction properties as observed with its compact being significantly harder than those prepared with pure hydroxypropyl methyl cellulose (HPMC) K4M. X-ray microtomography showed that the compacts produced were homogenous in nature, however, swelling studies showed failure of the compacts at the highest concentration of absolute ethanol used (40% v/v). Dissolution studies showed similarity at all levels of alcohol tested (f2 = 57-91) in simulated gastric (0.1 N HCl, pH 1.2) and intestinal fluids (phosphate buffer, pH 6.8) for the HPMC compacts whereas dissimilarity only occurred for the SG compacts at the highest alcohol concentration in both media (f2 = 35). The suitability of SG as a matrix former that can resist alcoholic effects therefore makes it suitable as an alternative polymer with wider applications for drug delivery.


Assuntos
Liberação Controlada de Fármacos , Etanol/química , Derivados da Hipromelose/química , Sesamum/química , Teofilina/química , Química Farmacêutica , Preparações de Ação Retardada , Análise Diferencial Térmica , Tomografia com Microscopia Eletrônica , Difração de Pó , Reologia , Comprimidos/química
8.
Int J Pharm ; 532(1): 352-364, 2017 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-28903068

RESUMO

Co-administration of drugs with alcohol can affect the plasma concentration of drugs in patients. It is also known that the excipients used in the formulation of drugs may not always be resistant to alcohol. This study evaluates effect of varying alcohol concentrations on theophylline release from two grades of Grewia mollis polysaccharides. X-ray microtomography showed that native polysaccharide formulation compacts were not homogenous after the mixing process resulting in its failure in swelling studies. Removal of starch from the native polysaccharide resulted in homogenous formulation compacts resistant to damage in high alcoholic media in pH 6.8 (40%v/v absolute ethanol). Destarched polymer compacts had a significantly higher hardness (375N) than that of the native polysaccharide (82N) and HPMC K4M (146N). Dissolution studies showed similarity at all levels of alcohol tested (f2=57-91) in simulated gastric media (pH 1.2). The dissolution profiles in the simulated intestinal fluids were also similar (f2=60-94), with the exception of the native polysaccharide in pH 6.8 (40%v/v absolute ethanol) (f2=43). This work highlights the properties of Grewia polysaccharide as a matrix former that can resist high alcoholic effects therefore; it may be suitable as an alternative to some of the commercially available matrix formers with wider applications for drug delivery as a cheaper alternative in the developing world.


Assuntos
Etanol/química , Grewia , Gomas Vegetais/química , Preparações de Ação Retardada/química , Liberação Controlada de Fármacos , Pós , Reologia , Solubilidade , Comprimidos , Teofilina/química
9.
J Wound Care ; 26(8): 470-475, 2017 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-28795892

RESUMO

OBJECTIVE: The use of cold atmospheric pressure plasma (CAPP) as a new therapeutic option to aid the healing of chronic wounds appears promising. Currently, uncertainty exists regarding their classification as medical device or medical drug. Because the classification of CAPP has medical, legal, and economic consequences as well as implications for the level of preclinical and clinical testing, the correct classification is not an academic exercise, but an ethical need. METHOD: A multidisciplinary team of physicians, surgeons, pharmacists, physicists and lawyers has analysed the physical and technical characteristics as well as legal conditions of the biological action of CAPP. RESULTS: It was concluded that the mode of action of the locally generated CAPP, with its main active components being different radicals, is pharmacological and not physical in nature. CONCLUSION: Depending on the intended use, CAPP should be classified as a drug, which is generated by use of a medical device directly at the point of therapeutic application.


Assuntos
Pressão Atmosférica , Temperatura Baixa , Equipamentos e Provisões/classificação , Preparações Farmacêuticas/classificação , Gases em Plasma/uso terapêutico , Infecção dos Ferimentos/terapia , Humanos
10.
BMC Infect Dis ; 17(1): 350, 2017 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-28514947

RESUMO

BACKGROUND: Chlorhexidine (CHG) penetrates poorly into skin. The purpose of this study was to compare the depth of CHG skin permeation from solutions containing either 2% (w/v) CHG and 70% (v/v) isopropyl alcohol (IPA) or 2% (w/v) CHG, 70% (v/v) IPA and 2% (v/v) 1,8-cineole. METHODS: An ex-vivo study using Franz diffusion cells was carried out. Full thickness human skin was mounted onto the cells and a CHG solution, with or without 2% (v/v) 1,8-cineole was applied to the skin surface. After twenty-four hours the skin was sectioned horizontally in 100 µm slices to a depth of 2000 µm and the concentration of CHG in each section quantified using high performance liquid chromatography (HPLC). The data were analysed with repeated measures analysis of variance. RESULTS: The concentration of CHG in the skin on average was significantly higher (33.3% [95%, CI 1.5% - 74.9%]) when a CHG solution which contained 1,8-cineole was applied to the skin compared to a CHG solution which did not contain this terpene (P = 0.042). CONCLUSIONS: Enhanced delivery of CHG can be achieved in the presence of 1,8-cineole, which is the major component of eucalyptus oil. This may reduce the numbers of microorganisms located in the deeper layers of the skin which potentially could decrease the risk of surgical site infection.


Assuntos
Clorexidina/farmacocinética , Cicloexanóis/farmacocinética , Monoterpenos/farmacocinética , Absorção Cutânea/efeitos dos fármacos , 2-Propanol/administração & dosagem , 2-Propanol/química , Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/farmacocinética , Clorexidina/administração & dosagem , Clorexidina/química , Cicloexanóis/administração & dosagem , Cicloexanóis/química , Eucaliptol , Feminino , Humanos , Pessoa de Meia-Idade , Monoterpenos/administração & dosagem , Monoterpenos/química , Soluções/química
11.
Int J Pharm ; 496(2): 689-98, 2015 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-26536530

RESUMO

Polysaccharides are suitable for application as hydrophilic matrices because of their ability to hydrate and swell upon contact with fluids, forming a gel layer which controls drug release. When extracted from plants, polysaccharides often contain significant quantities of starch that impacts upon their functional properties. This study aimed to evaluate differences in swelling, erosion and drug release from matrix tablets prepared from grewia gum (GG) and starch-free grewia gum (GDS) extracted from the stems of Grewia mollis. HPMC was used as a control polymer with theophylline as a model drug. Swelling, erosion, and in-vitro release were performed in deionized water, pH 1.2 and pH 6.8 media. The Vergnaud and Krosmeyer-Peppas model were used for swelling and drug release kinetics, respectively. However, linear regression technique was used to determine the erosion rate. GDS compacts were significantly harder than the native GG and HPMC compacts. GDS matrices exhibited the fastest erosion and drug release in deionised water and phosphate buffer compared with the GG and HPMC. At pH 1.2, GDS exhibited greater swelling than erosion, and drug release was similar to GG and HPMC. This highlights the potential of GDS as a matrix for controlled release similar to HPMC and GG at pH 1.2 but with a more rapid release at pH 6.8. GDS may have wider application in reinforcing compacts with relatively low mechanical strength.


Assuntos
Liberação Controlada de Fármacos , Grewia , Extratos Vegetais/síntese química , Gomas Vegetais/síntese química , Amido/síntese química , Química Farmacêutica , Força Compressiva , Extratos Vegetais/farmacocinética , Gomas Vegetais/farmacocinética , Caules de Planta , Amido/farmacocinética , Comprimidos
13.
J Antimicrob Chemother ; 70(8): 2255-60, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25904727

RESUMO

OBJECTIVES: The antimicrobial efficacy of an iodine-impregnated incise drape against MRSA was evaluated in a skin model. The permeation of iodine from this drape into the skin was also assessed. METHODS: The antimicrobial efficacy was evaluated in ex vivo studies following application of the surgical incise drape for various times on the surface of donor skin, which was inoculated with either 1 × 10(3) or 1 × 10(6) cfu MRSA/cm(2) skin and mounted on Franz diffusion cells. In some experiments the MRSA-inoculated skin was pre-incubated for 18 h at room temperature prior to applying the drape. Permeation of iodine into the skin using this model was also determined following application of the incise drape for 6 h. RESULTS: The iodine-impregnated drape demonstrated antimicrobial activity compared with the non-use of drape. This reached significance when a high inoculum of MRSA was applied with no pre-incubation period and when a low inoculum of MRSA was applied with a pre-incubation period (P = 0.002 and P = 0.014, respectively). Furthermore, in experiments wherein a high inoculum of MRSA was applied with no pre-incubation period, the iodine-impregnated drape demonstrated superior antimicrobial activity compared with the use of a non-antimicrobial drape (P < 0.001). MIC and MBC values of iodine were attained to 1500 µm below the skin surface. CONCLUSIONS: The iodine-impregnated surgical incise drape had detectable antimicrobial activity. Furthermore, iodine penetrated into the deeper layers of the skin. This property should suppress microbial regrowth at and around a surgical incision site, making its use preferable to the use of a standard drape or non-use of a drape.


Assuntos
Anti-Infecciosos/farmacologia , Iodo/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/microbiologia , Campos Cirúrgicos , Adulto , Idoso , Anti-Infecciosos/farmacocinética , Feminino , Humanos , Iodo/farmacocinética , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Modelos Biológicos
14.
Diabet Med ; 31(9): 1039-46, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24684407

RESUMO

AIMS: We aimed to determine whether the presence of hepatic steatosis and/or non-alcoholic fatty liver disease was associated with decline in renal function or onset of microalbuminuria in a cohort of people with Type 2 diabetes, including those managed in both primary and secondary care. METHODS: Nine hundred and thirty-three patients from the Edinburgh Type 2 Diabetes Study, a cohort of Scottish men and women aged 60-74 years with Type 2 diabetes, underwent assessment for hepatic steatosis by liver ultrasonography 1 year after recruitment. Non-alcoholic fatty liver disease was defined as the presence of steatosis following exclusion of secondary causes of liver disease. Patients were followed for 4 years and decline in renal function was assessed by the change in estimated glomerular filtration rate over time. RESULTS: Of the 933 subjects, 530 had hepatic steatosis and, of those with hepatic steatosis, 388 had non-alcoholic fatty liver disease. Neither hepatic steatosis nor non-alcoholic fatty liver disease were significantly associated with rate of decline in renal function, with the mean rate of decline in estimated glomerular filtration rate being -1.55 ml min(-1) 1.73 m(-2) per year for participants with hepatic steatosis compared with -1.84 ml min(-1) 1.73 m(-2) for those without steatosis (P = 0.19). Similar results were obtained when the analysis was restricted to participants with and without non-alcoholic fatty liver disease (-1.44 vs. -1.64 ml min(-1) 1.73 m(-2) per year, respectively; P = 0.44). Additionally, neither hepatic steatosis nor non-alcoholic fatty liver disease were associated with the onset or regression of albuminuria during follow-up (all P ≥ 0.05). CONCLUSIONS: The presence of hepatic steatosis/non-alcoholic fatty liver disease was not associated with decline in renal function during a 4-year follow-up in our cohort of older people with Type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Taxa de Filtração Glomerular , Falência Renal Crônica/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Idoso , Albuminúria/epidemiologia , Progressão da Doença , Fígado Gorduroso/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Escócia/epidemiologia , População Branca/estatística & dados numéricos
15.
Drug Dev Ind Pharm ; 38(1): 93-103, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22118222

RESUMO

AIM: Salt formation is a widely used approach to improve the physicochemical and solid state properties of an active pharmaceutical ingredient. In order to better understand the relationships between the active drug, the selected counterion and the resultant salt form, crystalline salts were formed using four different carboxylic acid drugs and a closely related series of amine counterions. Thirty-six related crystalline salts were prepared, characterized and the relationship between solubility and dissolution behaviour and other properties of the salt and the counterion studied. METHODS: Salts of four model acid drugs, gemfibrozil, flurbiprofen, ibuprofen and etodolac were prepared using the counterions butylamine, hexylamine, octylamine, benzylamine, cyclohexylamine, tert-butylamine, 2-amino-2-methylpropan-1-ol, 2-amino-2-methylpropan-1,3-diol and tris(hydroxymethyl)aminomethane. Salt formation was confirmed, the salts were characterized and their corresponding solubilities determined and rationalized with respect to the counterions' properties. RESULTS AND CONCLUSION: The properties of the salt highly dependent on the nature of the counterion and, although there is considerable variation, some general conclusion can be drawn. For the alkyl amines series, increasing chain length leads to a reduction in solubility across all the acidic drugs studied and a reduction in melting point, thus contradicting simplistic relationships between solubility and melting point. Small, compact counterions consistently produce crystalline salts with high melting point accompanied with a modest improvement in solubility and the nature of hydrogen bonding between the ions has a major impact on the solubility.


Assuntos
Ácidos Carboxílicos/química , Preparações Farmacêuticas/química , Sais/química , Aminas/química , Química Farmacêutica/métodos , Cristalização/métodos , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Íons/química , Solubilidade , Temperatura de Transição
16.
J Antimicrob Chemother ; 64(6): 1219-25, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19837714

RESUMO

OBJECTIVES: Effective disinfection and antisepsis is pivotal in preventing infections within the healthcare setting. Chlorhexidine digluconate (CHG) is a widely used disinfectant/antiseptic possessing broad-spectrum antimicrobial activity; however, its penetration into bacterial biofilms and human skin is poor. The aim of this study was to investigate the antimicrobial efficacy of crude eucalyptus oil (EO) and its main component 1,8-cineole (a recognized permeation enhancer), alone and in combination with CHG, against a panel of clinically relevant microorganisms grown in planktonic and biofilm cultures. METHODS: MICs and minimum bactericidal/fungicidal concentrations were determined for each microorganism grown in suspension and biofilm using microbroth dilution and ATP bioluminescence, respectively. Chequerboard assays were used to determine synergistic, indifferent or antagonistic interactions between CHG and EO or 1,8-cineole. RESULTS: Antimicrobial activity was demonstrated by CHG, EO and 1,8-cineole; however, CHG was significantly more active against microorganisms in both planktonic and biofilm modes of growth (P < 0.05). Crude EO was significantly more efficacious against microorganisms grown in suspension compared with 1,8-cineole (P < 0.05). Synergistic activity was demonstrated between CHG and both EO and 1,8-cineole against suspensions of Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Escherichia coli and Candida albicans, and biofilm cultures of MRSA and Pseudomonas aeruginosa. CONCLUSIONS: In conclusion, CHG may be combined with either crude EO or its major component 1,8-cineole for enhanced, synergistic antimicrobial activity against a wide range of microorganisms in planktonic and biofilm modes of growth; however, the superior antimicrobial efficacy associated with crude EO alone, compared with 1,8-cineole, favours its combination with CHG.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Clorexidina/análogos & derivados , Cicloexanóis/farmacologia , Monoterpenos/farmacologia , Óleos de Plantas/farmacologia , Antibacterianos/isolamento & purificação , Antifúngicos/isolamento & purificação , Biofilmes/efeitos dos fármacos , Clorexidina/farmacologia , Cicloexanóis/isolamento & purificação , Interações Medicamentosas , Escherichia coli/efeitos dos fármacos , Eucaliptol , Eucalyptus/química , Humanos , Testes de Sensibilidade Microbiana , Monoterpenos/isolamento & purificação , Óleos de Plantas/isolamento & purificação , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
17.
Nephron Clin Pract ; 112(4): c213-21, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19546580

RESUMO

Diabetic nephropathy is the most common cause of end-stage renal disease in the Western world. There is evidence for a genetic susceptibility to diabetic kidney disease, but despite intensive research efforts it has proved difficult to identify the causative genes. Improvements in genotyping technologies have made genome-wide association studies (GWAS), employing hundreds of thousands of single nucleotide polymorphisms, affordable. Recently, such scans have advanced understanding of the genetics of common complex diseases, finding more than 100 novel susceptibility variants for diverse disorders including type 1 and 2 diabetes, coronary heart disease, Crohn's disease and rheumatoid arthritis. In this review, type 2 diabetes is highlighted to illustrate how genome-wide association studies have been used to study the genetics of complex multifactorial conditions; in addition, diabetic nephropathy will be used to demonstrate how similar scans could be employed to detect genetic factors predisposing to kidney disease. The identification of such variants would permit early identification of atrisk patients, enabling targeting of therapy and a move towards primary prevention. In addition, these powerful research methodologies may identify genes that were not previously known to predispose to nephropathy, thereby enhancing our understanding of the pathophysiology of renal disorders and potentially leading to novel therapeutic approaches.


Assuntos
Marcadores Genéticos/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Nefropatias/epidemiologia , Nefropatias/genética , Modelos Genéticos , Humanos
19.
J Antimicrob Chemother ; 62(5): 1031-6, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18703525

RESUMO

OBJECTIVES: Effective skin antisepsis and disinfection of medical devices are key factors in preventing many healthcare-acquired infections associated with skin microorganisms, particularly Staphylococcus epidermidis. The aim of this study was to investigate the antimicrobial efficacy of chlorhexidine digluconate (CHG), a widely used antiseptic in clinical practice, alone and in combination with tea tree oil (TTO), eucalyptus oil (EO) and thymol against planktonic and biofilm cultures of S. epidermidis. METHODS: Antimicrobial susceptibility assays against S. epidermidis in a suspension and in a biofilm mode of growth were performed with broth microdilution and ATP bioluminescence methods, respectively. Synergy of antimicrobial agents was evaluated with the chequerboard method. RESULTS: CHG exhibited antimicrobial activity against S. epidermidis in both suspension and biofilm (MIC 2-8 mg/L). Of the essential oils thymol exhibited the greatest antimicrobial efficacy (0.5-4 g/L) against S. epidermidis in suspension and biofilm followed by TTO (2-16 g/L) and EO (4-64 g/L). MICs of CHG and EO were reduced against S. epidermidis biofilm when in combination (MIC of 8 reduced to 0.25-1 mg/L and MIC of 32-64 reduced to 4 g/L for CHG and EO, respectively). Furthermore, the combination of EO with CHG demonstrated synergistic activity against S. epidermidis biofilm with a fractional inhibitory concentration index of <0.5. CONCLUSIONS: The results from this study suggest that there may be a role for essential oils, in particular EO, for improved skin antisepsis when combined with CHG.


Assuntos
Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Clorexidina/análogos & derivados , Óleos de Plantas/farmacologia , Staphylococcus epidermidis/efeitos dos fármacos , Timol/farmacologia , Clorexidina/farmacologia , Sinergismo Farmacológico , Eucalyptus/química , Melaleuca/química , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos
20.
Antimicrob Agents Chemother ; 52(10): 3633-6, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18676882

RESUMO

This study evaluated a model of skin permeation to determine the depth of delivery of chlorhexidine into full-thickness excised human skin following topical application of 2% (wt/vol) aqueous chlorhexidine digluconate. Skin permeation studies were performed on full-thickness human skin using Franz diffusion cells with exposure to chlorhexidine for 2 min, 30 min, and 24 h. The concentration of chlorhexidine extracted from skin sections was determined to a depth of 1,500 microm following serial sectioning of the skin using a microtome and analysis by high-performance liquid chromatography. Poor penetration of chlorhexidine into skin following 2-min and 30-min exposures to chlorhexidine was observed (0.157 +/- 0.047 and 0.077 +/- 0.015 microg/mg tissue within the top 100 microm), and levels of chlorhexidine were minimal at deeper skin depths (less than 0.002 microg/mg tissue below 300 microm). After 24 h of exposure, there was more chlorhexidine within the upper 100-microm sections (7.88 +/- 1.37 microg/mg tissue); however, the levels remained low (less than 1 microg/mg tissue) at depths below 300 microm. There was no detectable penetration through the full-thickness skin. The model presented in this study can be used to assess the permeation of antiseptic agents through various layers of skin in vitro. Aqueous chlorhexidine demonstrated poor permeation into the deeper layers of the skin, which may restrict the efficacy of skin antisepsis with this agent. This study lays the foundation for further research in adopting alternative strategies for enhanced skin antisepsis in clinical practice.


Assuntos
Anti-Infecciosos Locais/farmacocinética , Clorexidina/farmacocinética , Pele/metabolismo , Administração Tópica , Anti-Infecciosos Locais/administração & dosagem , Cateterismo Venoso Central/métodos , Clorexidina/administração & dosagem , Feminino , Humanos , Técnicas In Vitro , Modelos Biológicos , Permeabilidade , Pele/efeitos dos fármacos , Pele/microbiologia , Soluções
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