ABSTRACT
Introduction: Curcumin is an important bioactive compound present in Curcuma longa, and is well known for its bioactivities such as anti-inflammatory, anticancer, antimicrobial, antiparasitic and antioxidant activity. The use of curcumin is limited owing to its poor solubility in water, fast degradation, and low bioavailability. This problem can be solved by using nano-curcumin, which is soluble in water and enhances its activity against various microbial pathogens and parasites.Areas covered: We have reviewed curcumin, curcumin-loaded nanoparticles and their activities against various pathogenic microbes (antifungal, antiviral and antiprotozoal) and parasites, as curcumin has already demonstrated broad-spectrum antimicrobial activity. It has also inhibited biofilm formation by various bacteria including Pseudomonas aeruginosa. The antimicrobial activity of curcumin can be increased in the presence of light radiation due to its photo-excitation. Further, it has been found that the activity of curcumin nanoparticles is enhanced when used in combination with antibiotics. Finally, we discussed the toxicity and safety issues of curcumin.Expert opinion: Since many microbial pathogens have developed resistance to antibiotics, the combination of curcumin with different nanoparticles will prove to be a boon for their treatment. Moreover, curcumin and curcumin-loaded nanoparticles can also be used against various parasites.
Subject(s)
Anti-Infective Agents/pharmacology , Antiparasitic Agents/pharmacology , Curcumin/pharmacology , Animals , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/isolation & purification , Antiparasitic Agents/administration & dosage , Antiparasitic Agents/isolation & purification , Biological Availability , Curcuma/chemistry , Curcumin/administration & dosage , Curcumin/isolation & purification , Drug Resistance, Microbial , Humans , Nanoparticles , SolubilityABSTRACT
Nanoparticle-conjugated venom-toxins of venomous animals and its therapeutic efficacy against emerging or neglecting diseases is a promising strategy. In this study, silver nanoparticles (AgNPs â¼50 nm, 0.081 mg mL-1) were studied against the neuromuscular blockade, myotoxic effects induced by Bothrops jararacussu venom (60 µg mL-1) and also against prokaryotic cells. The neurotoxicity was evaluated on ex vivo mouse phrenic nerve-diaphragm using traditional myographic technique, able to obtain functional contractile responses and to check the neurotransmission. The myotoxicity on mammalian cells was evaluated in muscles resulting from pharmacological assays using routine histological techniques and light microscopy. The toxicity to prokaryotic cells was evaluated on Salmonella typhimurium TA100 without metabolic activation. The in vitro preincubation model between AgNPs and venom was enough to abolish toxic effects of B. jararacussu venom, but mammalian cells were highly sensitive to AgNPs more than prokaryotic cells, by acting as dose-independently and dose-dependently parameters, respectively. These results allowed us to conclude that AgNPs showed promising activity as antivenom agent but for its safer use, the toxicity should be evaluated on experimental animals.
Subject(s)
Antidotes/pharmacology , Bothrops , Metal Nanoparticles/chemistry , Salmonella typhimurium/drug effects , Silver/pharmacology , Snake Venoms/toxicity , Animals , Antidotes/chemistry , Antidotes/toxicity , Diaphragm/drug effects , Diaphragm/innervation , Dose-Response Relationship, Drug , In Vitro Techniques , Male , Mice , Muscle Tonus/drug effects , Phrenic Nerve/drug effects , Silver/chemistry , Silver/toxicity , Snake Venoms/chemistryABSTRACT
The authors report the comparative antibacterial activity of silver nanoparticles synthesised by biological (using Fusarium oxysporum) and chemical routes in the presence and absence of pluronic F68 as a stabilising agent. The production of silver nanoparticles was evidenced by UV-visible spectra, with absorbance at about 420 nm in the case of both biological and chemical synthesis. X-ray diffraction pattern confirmed the presence of face-centred cubic structure (FCC plane). The nanoparticles characterised by transmission and scanning electron microscopy showed spherical silver nanoparticles with size range of 5-40 and 10-70 nm in the case of biologically and chemically synthesised nanoparticles, respectively. Addition of pluronic F68 showed the stabilisation of silver nanoparticles. Antibacterial efficacy of silver nanoparticles demonstrated different inhibitory activity against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Overall, biologically synthesised silver nanoparticles showed higher activity as compared with chemically synthesised nanoparticles. Silver nanoparticles synthesised in the presence of pluronic F68 by the chemical route exhibited synergism in antibacterial activity as compared with those synthesised without pluronic F68. On the contrary, biogenic silver nanoparticles without pluronic F68 showed higher antibacterial potential.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Bacterial Physiological Phenomena/drug effects , Excipients/chemistry , Metal Nanoparticles/administration & dosage , Poloxamer/chemical synthesis , Silver/administration & dosage , Anti-Bacterial Agents/administration & dosage , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Compounding/methods , Drug Synergism , Metal Nanoparticles/chemistry , Metal Nanoparticles/ultrastructure , Particle Size , Silver/chemistryABSTRACT
Noble metals and their compounds have been used as therapeutic agents from the ancient time in medicine for the treatment of various infections. Recently, much progress has been made in the field of nanobiotechnology towards the development of different kinds of nanomaterials with a wide range of applications. Among the metal nanoparticles, noble metal nanoparticles have demonstrated potential biomedical applications. Due to the small size, nanoparticles can easily interact with biomolecules both at surface and inside cells, yielding better signals and target specificity for diagnostics and therapeutics. Noble metal nanoparticles inspired the researchers due to their remarkable role in detection and treatment of dreadful diseases. In this review, we have attempted to focus on the biomedical applications of noble metal nanoparticles particularly, silver, gold, and platinum in diagnosis and treatment of dreaded diseases such as cancer, human immunodeficiency virus (HIV), tuberculosis (TB), and Parkinson disease. In addition, the role of silver nanoparticles (AgNPs) such as novel antimicrobials, gold nanoparticles (AuNPs) such as efficient drug carrier, uses of platinum nanoparticles (PtNPs) in bone allograft, dentistry, etc. have been critically reviewed. Moreover, the toxicity due to the use of metal nanoparticles and some unsolved challenges in the field have been discussed with their possible solutions.
Subject(s)
Drug Delivery Systems/instrumentation , Drug Therapy , Gold/chemistry , Metal Nanoparticles/therapeutic use , Platinum/chemistry , Silver/chemistry , Animals , Gold/pharmacology , Humans , Medicine/instrumentation , Medicine/methods , Metal Nanoparticles/chemistry , Platinum/pharmacology , Silver/pharmacologyABSTRACT
Ceftazidime is a broad spectrum antibiotic administered mainly by the parenteral route, and it is especially effective against Pseudomonas aeruginosa. The period of time in which serum levels exceed the Minimum Inhibitory Concentration (MIC) is an important pharmacodynamic parameter for its efficacy. One of the forms to extend this period is to administer the antibiotic by continuous infusion, after prior dilution in a Parenteral Solution (PS). The present work assessed the stability of ceftazidime in 5% glucose PS for 24 hours, combined or not with aminophylline, through High Performance Liquid Chromatography (HPLC). The physicochemical evaluation was accompanied by in vitro antimicrobial activity compared MIC test in the 24-hour period. Escherichia coli and Pseudomonas aeruginosa were the microorganisms chosen for the MIC comparison. The HPLC analysis confirmed ceftazidime and aminophylline individual stability on PS, while the MIC values were slightly higher than the mean described in the literature. When both drugs were associated in the same PS, the ceftazidime concentration by HPLC decreased 25% after 24 hours. Not only did the MIC values show high loss of antibiotic activity within the same period, but also altered MIC values immediately after the preparation, which was not detected by HPLC. Our results indicate that this drug combination is not compatible, even if used right away, and that PS might not be the best vehicle for ceftazidime, emphasizing the importance of the MIC evaluation for drug interactions.
Ceftazidima é um antimicrobiano administrado por via parenteral, que apresenta amplo espectro de ação, principalmente contra Pseudomonas aeruginosa. O tempo em que a concentração sérica de ceftazidima permanece acima da concentração mínima inibitória (MIC) é um importante parâmetro farmacodinâmico para a determinação da eficácia antimicrobiana e pode ser potencializado através da utilização de infusão contínua em soluções parenterais (PS). Este artigo visa a avaliar a estabilidade da ceftazidima em solução de glicose 5%, na presença e na ausência do fármaco aminofilina, através de cromatografia líquida de alta eficiência HPLC e MIC durante o período de 24 horas. Os microorganismos selecionados para a determinação do MIC foram Escherichia coli e Pseudomonas aeruginosa. Os ensaios em cromatógrafo líquido confirmaram a estabilidade dos fármacos ceftazidima e aminofilina quando são individualmente associados em PS, enquanto os valores de MIC ficaram maiores que os valores encontrados na literatura. Quando ambos os fármacos foram associados na mesma solução parenteral a concentração de ceftazidima obtida por HPLC diminuiu 25% depois de 24 horas. Os valores de MIC mostraram maior decaimento da atividade antimicrobiana neste mesmo período e também valores de MIC alterados nas soluções preparadas no tempo zero, decaimento este que não foi detectado em HPLC. Os resultados indicaram incompatibilidade na associação dos fármacos em PS, enfatizando a importância dos resultados de MIC para interações de fármacos.
Subject(s)
Ceftazidime/analysis , Aminophylline/analysis , Pharmaceutical Preparations/analysis , Microbial Sensitivity Tests , Chromatography, High Pressure Liquid , GlucoseABSTRACT
Parenteral solutions (PS) are one of the most commonly used drug delivery vehicles. Interactions among the drug, components in the drug's formulation, and the PS can result in the formation of inactive complexes that limit efficacy or increase side effects. The aim of this work was to evaluate possible interactions between the drugs and PS, assess drug stability and to identify degradation products after 20 h at room temperature. Furosemide (FSM) and Aminophylline (APN) were added to PS containing either 20 percent mannitol or 0.9 percent NaCl at pH 6.5-7.5 and 10-11. Their behavior was studied individually and as an admixture, after 1 h oxidation with H2O2, using a spectrophotometer and HPLC. Individually, FSM and APN added to 20 percent mannitol and 0.9 percent NaCl solutions had the highest stability at pH 10-11. When FSM and APN were combined, the behavior of FSM was similar to the behavior observed for the drug individually in the same solutions. With the drugs combined in 20 percent mannitol pH 10-11, HPLC showed that both drugs were stable after a 20 h period yielding two distinct peaks; in oxidized samples, the elution profile showed four peaks with retention times unrelated to the untreated samples.
Soluções parenterais de grande volume são frequentemente utilizadas no ambiente hospitalar para a veiculação de fármacos. No entanto, possíveis incompatibilidades entre as estruturas dos fármacos, em diferentes veículos de administração, podem gerar possíveis associações antagônicas ou sinérgicas, resultando em alterações das propriedades físico-químicas, consequentemente, dos efeitos farmacológicos e das respostas clínicas esperadas. Este artigo avaliou a estabilidade e a possível formação de produtos de degradação entre os fármacos furosemida e aminofilina quando estes foram veiculados em soluções parenterais, após o preparo e após o período de 20 h. Furosemida e aminofilina foram adicionadas às soluções de 20 por cento manitol e 0,9 por cento NaCl nos valores de pH 6,5-7,5 e 10-11. A estabilidade dos fármacos foi avaliada individualmente, combinada e após degradação com peróxido de hidrogênio através de espectrofotometria de UV e HPLC. Furosemida e aminofilina individualmente avaliadas mostraram alta estabilidade em ambas as soluções estudadas nos valores de pH 10-11. Quando os fármacos foram combinados o comportamento da furosemida foi similar ao observado na ausência de aminofilina. Os fármacos combinados em 20 por cento manitol pH10-11 por HPLC foram estáveis após o período de 20 h. Após degradação o perfil de cromatograma encontrado foi diferente do observado na ausência de degradação mostrando que o método é indicativo de estabilidade.
Subject(s)
Aminophylline/analysis , Aminophylline/adverse effects , Furosemide/analysis , Furosemide/adverse effects , Infusions, Parenteral/adverse effects , Infusions, Parenteral/methods , Infusions, Parenteral , Chromatography, High Pressure Liquid , Spectrophotometry , Time FactorsABSTRACT
Diante da extensa utilização de fármacos associados às soluções parenterais de grande volume (SPGV) e muitas vezes da impossibilidade da administração dos mesmos em diferentes veículos de infusão, sejam pela perda da estabilidade ou por insolubilidade destes, a utilização de copolímeros como carreadores de fármacos vêm a favorecer a associação destes às SPGV. Este trabalho visa avaliar a estabilidade dos fármacos ceftazidima e aminofilina nas SPGV carreados pelo copolímero Pluronic® F68 e o estudo da GFP como potencial biossensor da estabilidade de fármacos nas SPGV. A estabilidade dos fármacos ceftazidima (320ug/mL) e aminofilina (160ug/mL) em SPGV foi avaliada, na presença e na ausência de Pluronic® F68, através da utilização de HPLC logo após preparo e após período de 24hs, usando sistema Schimadzu LC10, LC-solution software, Schimadzu C18, fluxo 0,5mL/min, detecção em λ=255nm (ceftazidima) e λ=275nm (aminofilina), volume de injeção 20uL, 25ºC. A determinação da concentração mínima inibitória (CMI) foi realizada em amostras de ceftazidima (240ug/mL) na presença e na ausência de Pluronic® em SPGV de 5% glicose usando E. coli ATCC 25922 e P.eruginosa ATCC 9721 na concentração de 106UFC/mL . Pluronic® F68 foi utilizado nas amostras para avaliação da estabilidade dos fármacos ceftazidima e aminofilina na concentração 10% m/m. Resultados mostraram uma incompatibilidade entre a associação dos fármacos em SPGV de 5% glicose, com perda de concentração de 25% do fármaco ceftazidima na ausência de Pluronic®. Nos ensaios de CMI realizados com fármaco ceftazidima em SPGV de 5% glicose observou-se uma melhora dos valores de CMI quando o fármaco foi associado ao copolímero Pluronic® para ambos os microrganismos estudados. O estudo da GFP mostrou que fatores como (i) as propriedades físico-químicas dos fármacos, (ii) valores de pH das soluções e (iii) interações entre a proteína e as SPGV, podem favorecer mudanças de intensidade de fluorescência da GFP...
Drug association administered through parenteral solutions is a common hospital practice. Copolymers as carriers in parenteral solutions may allow originally unstable or insoluble drug combinations, or even improve their action. The aim of this work was to evaluate the stability of ceftazidime and aminophylline in parenteral solutions carried by Pluronic® F68, besides the application of the green fluorescent protein as a biossensor of drug stability. To evaluate the stability of ceftazidime (320 µg/mL) and aminophylline (160 µg/mL) carried by Pluronic® F68 (10%) in parenteral solutions, HPLC measurements were made immediately after the drug mixture preparation and after 24 hours, detected at λ=255nm (ceftazidime) and λ=275nm (aminophylline). In addition, minimal inhibitory concentration test (MIC) was used to determine the biological activity of ceftazidime (240 µg/mL) in 5% glucose parenteral solution, with or without Pluronic® F68 (10%). The strains tested by MIC were E. coli ATCC 25922 and P.aeruginosa ATCC 9721 (106UFC/mL). The HPLC experiments showed incompatibility of ceftazidime and aminophylline associated in 5% glucose parenteral solution, with 25% loss for ceftazidime without Pluronic® F68. MIC analysis for ceftazidime, with or without aminophylline, showed that lower antibiotic concentration values were required to inhibit E. coli and P.aeruginosa growth, when the copolymer Pluronic® F68 was present in the samples. It was also showed that physical chemical drugs alterations, pH values and protein-parenteral solution interactions can change GFP fluorescence intensity (detected by espectrofluorimeter λex=394nm, λem=509nm). These data endorse the potential of this protein as a biosensor of drug stability in parenteral solutions.
