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1.
Curr Pharm Des ; 27(42): 4300-4314, 2021.
Article in English | MEDLINE | ID: mdl-34042031

ABSTRACT

Surfactants are amphiphilic molecules of great interest in the pharmaceutical field which are used in combination with other adjuvants to solubilize poorly soluble drugs, improve their dissolution profile, promote permeation, improve drug delivery, enhance stabilization, among other characteristics. Literature shows that surfactants are included in several pharmaceutical compositions: tablets, solid dispersions, emulsions, microemulsions, nanoemulsions, liposomes and niosomes. This review aims to elucidate the different classes of surfactants based on their charges (cationic, anionic, nonionic, zwitterionic, and dimeric), the micelles formation process, and how surfactant molecules geometry can affect this phenomenon. Moreover, current studies regarding the benefits of surfactants in the development of formulations are presented. Finally, a discussion on how charges and chain length of surfactants can affect the stratum corneum epithelial cells leading to increased permeation or skin irritability is reported.


Subject(s)
Micelles , Surface-Active Agents , Drug Delivery Systems , Emulsions , Humans , Skin Absorption
2.
AAPS PharmSciTech ; 21(8): 288, 2020 Oct 18.
Article in English | MEDLINE | ID: mdl-33073311

ABSTRACT

Nanostructured lipid carriers (NLC) are aqueous dispersions of nanoparticles formed by solid and liquid lipids. In this study, NLC containing an organic UV filter, bemotrizinol, were developed for sunscreen formulation using carnauba wax and caprylic/capric triglycerides through ultrasonication technique. A Box-Behnken design was used to evaluate the influence of three variables on the particle size with the purpose of choosing the best system for further characterization. The particle size decreased as the surfactant concentration increased, reaching an average size of 122.4 ± 0.3 nm at 30 days of storage. Scanning electron microscopy showed intact and spherical particles. Thermal analysis and Fourier-transform infrared spectroscopy suggest that bemotrizinol was incorporated into the NLC. The X-ray diffraction showed a reduction in the crystallinity of the NLC. In vitro analysis indicated an improvement in the photoprotective activity of bemotrizinol when incorporated into NLC. These findings suggest a promising, stable, and biocompatible system.


Subject(s)
Drug Carriers/chemistry , Lipids/chemistry , Nanostructures/chemistry , Phenols/chemistry , Sunscreening Agents/chemistry , Triazines/chemistry , Waxes/chemistry , Microscopy, Electron, Scanning , X-Ray Diffraction
3.
Eur J Pharm Sci ; 155: 105547, 2020 Dec 01.
Article in English | MEDLINE | ID: mdl-32927070

ABSTRACT

The N-acylhydrazone subunit is considered a privileged structure in medicinal chemistry for its importance in pharmaceutical research. Also, alternative methods to deliver these molecules have a great pharmaceutical interest. Therefore, the objective of this work was to encapsulate JR19, an N-acyl hydrazone subunit, into chitosan films and evaluate several properties relevant for transdermal delivery, including biocompatibility using in vitro tests. CHI + JR19 film demonstrates greater strength, flexibility, water absorption capacity, low contact angle and higher surface roughness when compared to CHI. Agar diffusion and 3-(4,5-dimethyl)-2,5-diphenyl tetrazolium bromide (MTT) assay show the absence of cytotoxicity and the higher cell viability for CHI + JR19 films. Therefore, the addition of JR19 in the system positively influenced mechanical properties and granted better compatibility with biological environments, showing the potential to treat skin inflammation.


Subject(s)
Chitosan , Pharmaceutical Preparations , Administration, Cutaneous , Cell Survival , Chemistry, Pharmaceutical , Surface Properties
4.
Curr Pharm Des ; 26(33): 4048-4055, 2020.
Article in English | MEDLINE | ID: mdl-32133957

ABSTRACT

Medicinal plants produce secondary metabolites with special biological activities, which may be used as new therapeutic alternatives. For instance, tea tree essential oil (TTO) was shown to exert antimicrobial, antifungal, anthelmintic, antiviral, anti-tumor and anti-inflammatory activities. Due to their thermal instability, active principles can be easily degraded by physicochemical processes; therefore, they must be protected to increase their time of action and improve their controlled release. The aim of this review is to discuss formulations incorporating encapsulated TTO as the active ingredient. Micro and nanoencapsulated systems proved to be more thermostable than TTO and to exert better antimicrobial, antifungal, antiparasitic and larvicidal effects. Nanoencapsulation also reduced oil toxicity. Emulsified and hybrid systems developed by various methods showed improved repellent, antibacterial, antifungal and anti-inflammatory activities, thereby proving promising for the pharmaceutical industry. Liposomal formulations produced by hydration of lipid films exhibited constant rate of terpinen-4-ol release. In addition, their incorporation into biomaterials, such as sponges, nanofibers and films, showed great potential for treating infections. Mainly due to the advantages of their incorporation into new drug delivery systems over conventional formulations, there is an interest in the development of systems containing TTO as a pharmaceutical ingredient of plant origin.


Subject(s)
Anti-Infective Agents , Melaleuca , Tea Tree Oil , Antifungal Agents , Drug Delivery Systems , Humans , Tea Tree Oil/pharmacology
5.
Curr Pharm Des ; 26(33): 4163-4173, 2020.
Article in English | MEDLINE | ID: mdl-32156229

ABSTRACT

The encapsulation of bioactive compounds is an emerging technique for finding new medicines since it provides protection against ambient degradation factors before reaching the target site. Nanotechnology provides new methods for encapsulating bioactive compounds and for drug carrier development. Nanocarriers satisfactorily impact the absorption, distribution, metabolism, and excretion rate when compared to conventional carriers. The nanocarrier material needs to be compatible and bind to the drug and be bio-resorbable. In this context, the physicochemical characterization of encapsulated bioactive compounds is fundamental to guarantee the quality, reproducibility, and safety of the final pharmaceutical product. In this review, we present the physicochemical techniques most used today by researchers to characterize bioactive compounds in nanocarriers and the main information provided by each technique, such as morphology, size, degree of crystallinity, long-term stability, the efficacy of drug encapsulation, and the amount released as a function of time.


Subject(s)
Drug Carriers , Nanoparticles , Humans , Nanotechnology , Reproducibility of Results
6.
Oxid Med Cell Longev ; 2019: 1983137, 2019.
Article in English | MEDLINE | ID: mdl-31827669

ABSTRACT

Ethnomedicinal studies in the Amazon community and in the Northeast region of Brazil highlight the use of Libidibia ferrea fruits for the treatment of gastric problems. However, there are no data in the literature of this pharmacological activity. Thus, the aim of this paper is to provide a scientific basis for the use of the dry extract of L. ferrea pods (DELfp) for the treatment of peptic ulcers. Phytochemical characterization was performed by HPLC/MS. In vitro antioxidant activity was assessed using DPPH, ABTS, phosphomolybdenum, and superoxide radical scavenging activity. The gastroprotective activity, the ability to stimulate mucus production, the antisecretory activity, and the influence of -SH and NO compounds on the antiulcerogenic activity of DELfp were evaluated. The healing activity was determined by the acetic acid-induced chronic ulcer model. Anti-Helicobacter pylori activity was investigated. HPLC/MS results identified the presence of phenolic compounds, gallic acid and ellagic acid, in DELfp. The extract showed antioxidant activity in vitro. In ulcers induced by absolute ethanol and acidified ethanol, the ED50 values of DELfp were 113 and 185.7 mg/kg, respectively. DELfp (100, 200, and 400 mg/kg) inhibited indomethacin-induced lesions by 66.7, 69.6, and 65.8%, respectively. DELfp (200 mg/kg) reduced gastric secretion and H+ concentration in the gastric contents and showed to be independent of nitric oxide (NO) and dependent on sulfhydryl (-SH) compounds in the protection of the gastric mucosa. In the chronic ulcer model, DELfp reduced the area of the gastric lesion. DELfp also showed anti-H. pylori activity. In conclusion, DELfp showed antioxidant, gastroprotective, healing, and antiulcerogenic activities. The mechanism of these actions seems to be mediated by different pathways and involves the reduction of gastric secretion and H+ concentration, dependence on sulfhydryl compounds, and anti-H. pylori activity. All these actions support the medicinal use of this species in the management of peptic ulcers.


Subject(s)
Anti-Ulcer Agents/chemistry , Antioxidants/chemistry , Fabaceae/chemistry , Plant Extracts/chemistry , Acetic Acid/toxicity , Animals , Anti-Ulcer Agents/pharmacology , Anti-Ulcer Agents/therapeutic use , Chromatography, High Pressure Liquid , Fabaceae/metabolism , Female , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Helicobacter pylori/drug effects , Mass Spectrometry , Nitric Oxide/chemistry , Nitric Oxide/metabolism , Phenols/analysis , Plant Extracts/pharmacology , Rats , Rats, Wistar , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Stomach Ulcer/pathology , Sulfhydryl Compounds/chemistry , Sulfhydryl Compounds/metabolism
7.
Int J Pharm ; 506(1-2): 351-60, 2016 Jun 15.
Article in English | MEDLINE | ID: mdl-27130362

ABSTRACT

Microemulsion containing pentoxifylline was developed and characterized for use as a topical alternative to treat skin disorders. The transparent formulation was developed and optimized based on a pseudoternary phase diagram. Pentoxifylline-loaded microemulsion (PTX-ME) was composed of 44% Tween 80™/Brij 52™ mix as surfactants (S), 51% of caprylic/capric triglycerides as the oil phase (O) and 5% of water as aqueous phase (A). It was classified as an isotropic water-in-oil (W/O) system with droplets that had a heterogeneous spherical shape within the nanosized range (67.36±8.90nm) confirmed by polarized light microscopy, differential scanning calorimetry (DSC), transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis. In vitro studies using static diffusion Franz cells revealed that the release of PTX from ME followed the Higuchi kinetic model. Topical PTX-ME application developed superior anti-inflammatory activity when compared to the PTX solution, reducing the paw edema up to 88.83%. Our results suggested that this colloidal nanosystem is a promising agent for the delivery of pentoxifylline, increasing its ability to modulate the inflammatory aspects of skin disorders.


Subject(s)
Excipients/chemistry , Pentoxifylline/administration & dosage , Phosphodiesterase Inhibitors/administration & dosage , Administration, Cutaneous , Animals , Chemistry, Pharmaceutical/methods , Disease Models, Animal , Drug Liberation , Edema/drug therapy , Emulsions , Inflammation/drug therapy , Male , Nanoparticles , Particle Size , Pentoxifylline/chemistry , Pentoxifylline/pharmacokinetics , Phase Transition , Phosphodiesterase Inhibitors/chemistry , Phosphodiesterase Inhibitors/pharmacokinetics , Rats , Rats, Wistar , Skin Absorption , Surface-Active Agents/chemistry
8.
J Mol Graph Model ; 66: 26-40, 2016 05.
Article in English | MEDLINE | ID: mdl-27017426

ABSTRACT

Thaumatin-like proteins (TLPs) are enzymes with important functions in pathogens defense and in the response to biotic and abiotic stresses. Last identified olive allergen (Ole e 13) is a TLP, which may also importantly contribute to food allergy and cross-allergenicity to pollen allergen proteins. The goals of this study are the characterization of the structural-functionality of Ole e 13 with a focus in its catalytic mechanism, and its molecular allergenicity by extensive analysis using different molecular computer-aided approaches covering a) functional-regulatory motifs, b) comparative study of linear sequence, 2-D and 3D structural homology modeling, c) molecular docking with two different ß-D-glucans, d) conservational and evolutionary analysis, e) catalytic mechanism modeling, and f) IgE-binding, B- and T-cell epitopes identification and comparison to other allergenic TLPs. Sequence comparison, structure-based features, and phylogenetic analysis identified Ole e 13 as a thaumatin-like protein. 3D structural characterization revealed a conserved overall folding among plants TLPs, with mayor differences in the acidic (catalytic) cleft. Molecular docking analysis using two ß-(1,3)-glucans allowed to identify fundamental residues involved in the endo-1,3-ß-glucanase activity, and defining E84 as one of the conserved residues of the TLPs responsible of the nucleophilic attack to initiate the enzymatic reaction and D107 as proton donor, thus proposing a catalytic mechanism for Ole e 13. Identification of IgE-binding, B- and T-cell epitopes may help designing strategies to improve diagnosis and immunotherapy to food allergy and cross-allergenic pollen TLPs.


Subject(s)
Allergens/chemistry , Phylogeny , Plant Proteins/chemistry , Allergens/genetics , Amino Acid Sequence/genetics , Humans , Molecular Docking Simulation , Olea/chemistry , Olea/genetics , Plant Proteins/genetics , Sequence Homology, Amino Acid
9.
Curr Drug Deliv ; 13(6): 982-93, 2016.
Article in English | MEDLINE | ID: mdl-26549650

ABSTRACT

BACKGROUND: Amphotericin B eye drops are widely used in the treatment of ocular infections. However, amphotericin's toxicity leads to low patient compliance and aggravation of symptoms. This work describes the development of a microemulsion system containing amphotericin B, aiming for its use in ocular applications. METHODS: The microemulsion was developed by the titration technique. The physicochemical characteristics were determined with both loaded and unloaded amphotericin B-microemulsion. The nanostructures were analyzed by polarized light microscopy. The microdilution method was used to establish the minimum inhibitory concentration against fungal strains, and, therefore, evaluate the microemulsion activity. Additionally, in order to evaluate the microemulsion toxicity an in vitro toxicity assay against red blood cells was performed. RESULTS: The performed studies showed that the presence of amphotericin B loaded into the system did not induce serious changes in the physicochemical properties of the microemulsion when compared to the unloaded system. The spectrophotometric studies depicted amphotericin B-self-associated species, which allow predicting its behavior in vitro. The high pressure liquid chromatography results revealed high drug content entrapment in the microemulsion droplet. Finally, the amphotericin B-microemulsion in vitro susceptibility test showed high activity against Candida strains and a low toxicity profile against red blood cells when compared to Fungizone®. CONCLUSION: The physicochemical characterization of the microemulsion demonstrated that its characteristics are compatible with the topical ocular route, making it eligible for consideration as a new and interesting amphotericin B-deliverydosage form to be used as eye drop formulation.


Subject(s)
Amphotericin B/administration & dosage , Amphotericin B/pharmacology , Antifungal Agents/administration & dosage , Drug Carriers/administration & dosage , Emulsions/administration & dosage , Emulsions/chemistry , Ophthalmic Solutions/administration & dosage , Antifungal Agents/pharmacology , Drug Carriers/adverse effects , Drug Carriers/chemistry , Emulsions/adverse effects , Erythrocytes/drug effects , Microbial Sensitivity Tests , Nanostructures/administration & dosage , Nanostructures/adverse effects , Nanostructures/chemistry , Ophthalmic Solutions/adverse effects , Ophthalmic Solutions/chemistry , Particle Size
10.
Opt Express ; 21(4): 4396-404, 2013 Feb 25.
Article in English | MEDLINE | ID: mdl-23481973

ABSTRACT

In this work a novel approach in synchronization of electrooptic sampling systems for the ultra-broadband characterization of active mm-wave and THz devices is presented. The relative time jitter between sampled circuit and probing electrooptic head is eliminated by using a femtosecond laser system both as the generator of CW driving the device under test as well as the impulsively probing element. Previous ultra-broadband approaches were applicable to passive components driven by THz impulses, only. The presented system is more generally applicable to active mm-wave and THz components driven by conventional CW electronic sources. Broadband analysis on silicon nonlinear transmission line elements up to a frequency of 300 GHz is presented in order to illustrate the capabilities of the concept.


Subject(s)
Lasers , Signal Processing, Computer-Assisted/instrumentation , Telecommunications/instrumentation , Terahertz Radiation , Equipment Design , Equipment Failure Analysis , Sample Size
12.
J Biomed Nanotechnol ; 8(2): 290-300, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22515080

ABSTRACT

Amphotericin B remains the drug of choice for the treatment of most of the systemic fungal infections in immunodeficient patients. Because of the high incidence of adverse drug reactions the clinical use of Amphotericin B is rather limited. To reduce its toxicity new drug delivery systems has been suggested. Nevertheless, these carriers present several technological drawbacks that impair the development of a marketable product. The aim of this work was to develop an Amphotericin B microemulsion in order to increase its efficacy and decrease its toxicity compared to Fungizon, the widely know inexpensive micellar system of Amphotericin B. Amphotericin B loaded microemulsion showed an average size close to 300 nm by photon correlation spectroscopy. In the UV spectrum, the observation of the monomeric peak at 405 nm, which was independent of the sample dilution, revealed that the Amphotericin B molecules were strongly and individually bound to the microemulsion droplets. The new microemulsion formulation had the same efficacy than Fungizon against C. albicans. Concerning toxicity, Amphotericin B loaded microemulsion showed lower toxicity against human red blood cells compared to the commercial product. Taken together, these results suggested that microemulsion is an eligible drug carrier for Amphotericin B or other water insoluble molecules, and it has potential applications to targeting fungal cells. Additionally, a novel formulation of Amphotericin B-loaded microemulsion was prepared by a straightforward and fast procedure.


Subject(s)
Amphotericin B/chemistry , Amphotericin B/toxicity , Antifungal Agents/chemistry , Antifungal Agents/toxicity , Drug Carriers/chemistry , Drug Carriers/toxicity , Amphotericin B/pharmacology , Antifungal Agents/pharmacology , Candida albicans/drug effects , Cell Survival/drug effects , Drug Carriers/pharmacology , Emulsions/chemistry , Emulsions/pharmacology , Emulsions/toxicity , Erythrocytes/drug effects , Erythrocytes/metabolism , Hemoglobins/metabolism , Humans , Linear Models , Male , Nanoparticles/adverse effects , Nanoparticles/chemistry , Nanoparticles/toxicity , Particle Size , Potassium/blood , Spectrophotometry
13.
Opt Express ; 19(27): 26382-93, 2011 Dec 19.
Article in English | MEDLINE | ID: mdl-22274222

ABSTRACT

In the present paper we describe a high-power tunable solid-state dye laser setup that offers peak output power up to 800 mW around 575 nm with excellent long-time power stability and low noise level. The spectral width of the laser emission is less than 3 GHz and can be tuned over more than 30 nm. A nearly circular mode profile is achieved with an M(2) better than 1.4. The device can be integrated in a compact housing (dimensions are 60 × 40 × 20 cm(3)). The limitation of long-time power stability is mainly given by photo decomposition of organic dye molecules. These processes are analyzed in detail via spatially resolved micro-imaging and spectroscopic studies.


Subject(s)
Coloring Agents/chemistry , Computer-Aided Design , Lasers , Energy Transfer , Equipment Design , Equipment Failure Analysis
14.
Acta Cir Bras ; 22 Suppl 1: 57-63, 2007.
Article in English | MEDLINE | ID: mdl-17505657

ABSTRACT

PURPOSE: This study explores the potential of the simvastatin to ameliorate inflammation and infection in open infected skin wounds of rats. METHODS: Fourteen Wistar rats weighing 285 +/- 12g were used. The study was done in a group whose open infected skin wounds were treated with topical application of simvastatin microemulsion (SIM, n=7) and a second group with wounds treated with saline 0.9 % (SAL, n=7). A bacteriological exam of the wounds fluid for gram positive and gram negative bacteria, the tecidual expression of TNFá and IL-1â by immunohistochemical technique, and histological analysis by HE stain were performed. RESULTS: The expression of TNFa could be clearly demonstrated in lower degree in skin wounds treated with simvastatin (668.6 +/- 74.7 ìm(2)) than in saline (2120.0 +/-327.1 ìm(2)). In comparison, wound tissue from SIM group displayed leukocyte infiltration significantly lower than that observed in SAL group (p<0.05). Culture results of the samples taken from wound fluid on fourth post treatment day revealed wound infection in only one rat of group simvastatin (SIM), where Proteus mirabilis, Escherichia coli and Enterobacter sp were isolated. In the rats whose wounds were treated with saline (SAL), polymicrobial infection with more than 100,000 CFU/g was detected in all the wounds. CONCLUSION: In addition to its antiinflammatory properties, the protective effects of simvastatin in infected open skin wounds is able to reduce infection and probably has antibacterial action. The potential to treat these wounds with statins to ameliorate inflammation and infection is promising.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Simvastatin/therapeutic use , Surgical Wound Infection/drug therapy , Wound Healing/drug effects , Analysis of Variance , Animals , Anti-Bacterial Agents/pharmacology , Disease Models, Animal , Drug Evaluation, Preclinical , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Inflammation/drug therapy , Interleukin-1beta/metabolism , Random Allocation , Rats , Rats, Wistar , Simvastatin/pharmacology , Surgical Wound Infection/microbiology , Surgical Wound Infection/pathology , Tumor Necrosis Factor-alpha/metabolism
15.
Acta cir. bras ; Acta cir. bras;22(supl.1): 57-63, 2007. tab, ilus
Article in English | LILACS | ID: lil-449616

ABSTRACT

PURPOSE: This study explores the potential of the simvastatin to ameliorate inflammation and infection in open infected skin wounds of rats. METHODS: Fourteen Wistar rats weighing 285±12g were used. The study was done in a group whose open infected skin wounds were treated with topical application of sinvastatina microemulsion (SIM, n=7) and a second group with wounds treated with saline 0.9 percent (SAL, n=7). A bacteriological exam of the wounds fluid for gram positive and gram negative bacteria, the tecidual expression of TNFá and IL-1â by imunohistochemical technique, and histological analysis by HE stain were performed. RESULTS: The expression of TNFa could be clearly demonstrated in lower degree in skin wounds treated with simvastatin (668.6 ± 74.7 ìm²) than in saline (2120.0 ± 327.1 ìm²). In comparison, wound tissue from SIM group displayed leukocyte infiltration significantly lower than that observed in SAL group (p<0.05). Culture results of the samples taken from wound fluid on fourth post treatment day revealed wound infection in only one rat of group simvastatin (SIM), where Proteus mirabilis, Escherchia coli and Enterobacter sp were isolated. In the rats whose wounds were treated with saline (SAL), polymicrobial infection with more than 100,000 CFU/g was detected in all the wounds. CONCLUSION: In addition to its antiinflammatory properties, the protective effects of simvastatin in infected open skin wounds is able to reduce infection and probably has antibacterial action. The potential to treat these wounds with statins to ameliorate inflammation and infection is promising.


OBJETIVO: O presente estudo avaliou o potencial da sinvastatina para atenuar a inflamação e a infecção em feridas abertas infectadas de pele de ratos. MÉTODOS: Foram utilizados 14 ratos Wistar pesando 285±12g. O estudo foi realizado com um grupo de animais cujas feridas abertas infectadas foram tratadas com aplicação tópica de sinvastatina microemulsão (SIM, n=7) e um segundo grupo com feridas tratadas com solução salina 0,9 por cento (SAL n=7). Foi realizado exame bacteriológico do fluido das feridas para detecção de bactérias gram positivas e negativas, a expressão tecidual de TNFá e IL-1â por imunohistoquímica e análise histológica pela coloração H-E. RESULTADOS: A expressão do TNFa pode ser claramente demonstrada em menor grau nas feridas de pele tratadas com sinvastatina (668.6 ± 74.7 ìm²) do que no grupo salina (2120.0 ± 327.1 ìm²). Em comparação, os tecidos das feridas do grupo SIM mostrou infiltração leucocitária significantemente menor do que a observada no grupo SAL (p<0,05). O resultado das culturas realizadas no fluido das feridas no 4° dia de tratamento revelou infecção em apenas um rato do grupo sinvastatina (SIM), onde Proteus mirabilis, Escherchia coli e Enterobacter sp foram isolados. Nos ratos cujas feridas foram tratadas com solução salina (SAL), infecção polimicrobiana com mais de 100,000 UFC/g foi detectada em todas as feridas. CONCLUSÃO: Além de suas propriedades antiinflamatórias, o efeito protetor da sinvastatina em feridas abertas e infectadas de pele é capaz de reduzir a infecção e provavelmente tem ação antibacteriana. O potencial da droga para atenuar inflamação e infecção de feridas é promissor.


Subject(s)
Animals , Rats , Anti-Bacterial Agents/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Simvastatin/therapeutic use , Surgical Wound Infection/drug therapy , Wound Healing/drug effects , Analysis of Variance , Anti-Bacterial Agents/pharmacology , Disease Models, Animal , Drug Evaluation, Preclinical , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Inflammation/drug therapy , Interleukin-1beta/metabolism , Random Allocation , Rats, Wistar , Simvastatin/pharmacology , Surgical Wound Infection/microbiology , Surgical Wound Infection/pathology , Tumor Necrosis Factor-alpha/metabolism
16.
Curr Drug Deliv ; 2(2): 199-205, 2005 Apr.
Article in English | MEDLINE | ID: mdl-16305421

ABSTRACT

The aim of this work was to develop an in vitro experimental protocol for the evaluation of toxicity and efficacy of an amphotericin B (AmB) micelle system, Fungizone, which was previously diluted with a lipid based emulsion for parenteral use, named Lipofundin LCT/MCT-20%. Two cell models were used for the experiments: Red Blood Cells (RBC) from human donnors and Candida tropicalis (Ct). These models were used to perform the toxicity and activity of the Fungizone/ Lipofundin admixture (AmB-LP) and the Fungizone (AmB-M) alone. While potassium (K+) and hemoglobin leakage from RBC were the parameters used to evaluate the acute and chronic toxicity, respectively, the efficacy of AmB-LP and AmB-M were assessed by K+ leakage or cell survival rate (CSR) from Ct. The results show that the toxicity of AmB-LP to RBC was concentration dependent concerning the K+ leakage; while at high concentrations, 5 and 50 mg x mL(-1), the leakage was 50.91 +/- 2.09% and 95.71 +/- 0.64%, respectively, at a concentration of 0.5 mg x mL(-1) this value was 17.16 +/- 1.57% and the value tended to zero for the lowest concentration studied, 0.05 mg x mL(-1). Surprisingly, AmB-LP induced very low hemoglobin leakage for all concentrations studied. At the highest concentration, 50 mg x mL(-1), this value was around 3%. When the cell model was Ct, the results changed completely. Not only high concentrations of AmB-LP, but also lower ones were able to induce a K+ permeability of around 100%. The CSR parameter showed an inverse correlation with the concentration; high values, between 50 and 5 mg x mL(-1), resulted in a CSR of around 8%. On the other hand, for lower concentration values, 0.05 and 0.5 mg x mL(-1), this one was around 80%. The same profile of activity against Ct was found for AmB-M. Only a small variation was found for the K+ leakage at 0.05 mg x mL(-1) that presented a value of 96.99 +/- 2.53%. However, AmB-M seemed to be much more toxic than AmB-LP. Its induction of hemoglobin leakage started at 0.5 mg x mL(-1) and reached the 100% at 5 mg x mL(-1). K+ leakage results were worse. The intermediate concentrations of study, 0.5 and 5 mg x mL(-1), presented a significant increase compared to AmB-LP. All together these results reveal that the activity of AmB is not only concentration dependent, but also depends on the drug carrier in which this compound was inserted. The AmB-LP preparation showed the same efficacy as AmB-M, but with a low toxicity. Therefore, AmB-LP presented a higher therapeutic index that permits the administration of high concentration of AmB without revealing side effects. However, the simple mixture of two complex pharmaceutical entities, as micelles and emulsions, should be analyzed carefully to assure that physicochemical stability is not reduced and thereby cause a different biodistribution in vivo.


Subject(s)
Amphotericin B/administration & dosage , Amphotericin B/toxicity , Phospholipids/administration & dosage , Sorbitol/administration & dosage , Adult , Dose-Response Relationship, Drug , Drug Combinations , Erythrocytes/drug effects , Erythrocytes/metabolism , Female , Humans , Micelles , Potassium/metabolism
17.
Opt Lett ; 30(18): 2357-9, 2005 Sep 15.
Article in English | MEDLINE | ID: mdl-16196318

ABSTRACT

Unprecedented optical control of the surface plasmon polariton assisted transmission of terahertz radiation through subwavelength apertures is rendered possible by carrier-induced changes to the dielectric properties of a semiconductor grating. Although the study presented is static, the extension of our approach to dynamic switching and tuning is deemed straightforward, opening the way for the realization of ultrafast surface plasmon based devices.

18.
Acta Cir Bras ; 20 Suppl 1: 257-61, 2005.
Article in English | MEDLINE | ID: mdl-16186987

ABSTRACT

PURPOSE: Amphotericin B (AmB), an antifungal agent that presents a broad spectrum of activity, remains the gold standard in the antifungal therapy. However, sometimes the high level of toxicity forbids its clinical use. The aim of this work was to evaluate and compare the efficacy and toxicity in vitro of Fungizon (AmB-D) and two new different AmB formulations. METHODS: three products were studied: Fungizon, and two Fungizon /Lipofundin admixtures, which were diluted through two methods: in the first one, Fungizon was previously diluted with water for injection and then, in Lipofundin (AmB-DAL); the second method consisted of a primary dilution of AmB-D as a powder in the referred emulsion (AmB-DL). For the in vitro assay, two cell models were used: Red Blood Cells (RBC) from human donors and Candida tropicallis (Ct). The in vitro evaluation (K+ leakage, hemoglobin leakage and cell survival rate-CSR) was performed at four AmB concentrations (from 50 to 0.05 mg x L(-1)). RESULTS: The results showed that the action of AmB was not only concentration dependent, but also cellular type and vehicle kind dependent. At AmB concentrations of 50 mg x L(-1), although the hemoglobin leakage for AmB-D was almost complete (99.51), for AmB-DAL and AmB-DL this value tended to zero. The p = 0.000 showed that AmB-D was significantly more hemolytic. CONCLUSION: The Fungizon-Lipofundin admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented.


Subject(s)
Amphotericin B/pharmacology , Antifungal Agents/pharmacology , Parenteral Nutrition/standards , Phospholipids/pharmacology , Sorbitol/pharmacology , Amphotericin B/adverse effects , Analysis of Variance , Antifungal Agents/adverse effects , Candida tropicalis/drug effects , Drug Carriers , Drug Combinations , Erythrocytes/drug effects , Female , Hemoglobins/drug effects , Humans , In Vitro Techniques , Models, Biological , Phospholipids/adverse effects , Potassium/blood , Sorbitol/adverse effects , Treatment Outcome
19.
Acta cir. bras ; Acta cir. bras;20(supl.1): 257-261, 2005.
Article in English | LILACS | ID: lil-414652

ABSTRACT

OBJETIVO: A anfotericina B é um agente antifúngico de largo espectro bastante empregado na terapia antifúngica. Entretanto, esta molécula apresenta um alto nível de toxicidade que, na maioria das vezes, impede o seu uso contínuo na terapêutica médica. O objetivo deste artigo foi comparar a eficácia e a toxicidade in vitro do Fungizon™ (AmB-D) e de dois sistemas carreadores de AmB. MÉTODOS: Três produtos foram avaliados: o Fungizon™ , e dois sistemas oriundos da mistura entre o Fungizon™ e o Lipofundin™ , uma emulsão de uso parenteral. Tais sistemas foram obtidos por duas técnicas: Na primeira diluiu-se previamanete o Fungizon™ com água para injetáveis e em seguida inseriu-se o Lipofundin™ (AmB-DAL); o segundo método consistiu na diluíção extemporânea do Fungizon™ com a referida emulsão (AmB-DL). Dois modelos celulares foram empregados no estudo: os eritrócitos (RBC) oriundos de doadores humanos e a Candida tropicalis (Ct). A avaliação in vitro (liberação de K+ e hemoglobina, e o índice de sobrevivência celular-CSR) foi realizado com quatro concentrações de AmB (entre 50 e 0.05mg.L-1). RESULTADOS: Os resultados demonstram que a ação da AmB não só foi dependente da concentração como também variou de acordo com o modelo celular e o veículo que diluiu o Fungizon™ . Nas concentrações de 50 mg.L-1, apesar da liberação de hemoglobina ser quase que total para AmB-D (99.51), para a AmB-DAL e AmB-DL este valor tendeu a zero. Um p = 0.000 demonstrou que AmB-D foi significativamente mais hemolítico. CONCLUSÃO: A mistura Fungizon™ -Lipofundin™ aparenta ser um bom sistema para carrear a AmB tendo em vista seu elevado índice terapêutico demonstrado.


Subject(s)
Female , Humans , Amphotericin B/pharmacology , Antifungal Agents/pharmacology , In Vitro Techniques , Parenteral Nutrition/standards , Phospholipids/pharmacology , Sorbitol/pharmacology , Analysis of Variance , Amphotericin B/adverse effects , Antifungal Agents/adverse effects , Candida tropicalis/drug effects , Drug Carriers , Drug Combinations , Erythrocytes/drug effects , Hemoglobins/drug effects , Models, Biological , Phospholipids/adverse effects , Potassium/blood , Sorbitol/adverse effects , Treatment Outcome
20.
Opt Lett ; 29(14): 1680-2, 2004 Jul 15.
Article in English | MEDLINE | ID: mdl-15309858

ABSTRACT

We demonstrate that the extraordinary transmission of terahertz radiation through semiconductor gratings of subwavelength apertures can be switched completely by varying the temperature. The enhanced transmission, which is due to the resonant tunneling of surface plasmon polaritons that can be excited in semiconductors at terahertz frequencies, is controlled by thermally modifying the density of free carriers. The transmission through metal gratings cannot be switched in the same way since the carrier density is temperature independent. Thus semiconductors offer an interesting alternative to metals in enhancing the transmission of electromagnetic radiation.

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