Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

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 0.05mg.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.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

Modificação de membranas de quitosana por plasma para uso biológico

Chitosan membranes have been modified by plasma, utilizing the following gases: nitrogen (N2), methane (CH4), argon (Ar), oxygen (O2) and hydrogen. The modified membranes by plasma were compared to the unmodified ones. The membranes were characterized by absorption assay, contact angle, atomic force microscopy (AFM). Also, permeability assay of sodium sulfamerazine from such membranes were carried out. Through the absorption assay and contact angle it was possible to obtain information of the wettability of the membranes and what changes the plasma treatment can promote in relation to it. The plasma treatment using oxygen promoted increase of the wetability and swelling while the samples treated with methane decrease of the wetability and swelling. Through the Optical Emission Spectroscopy (OES) it was possible to identify which species were present in the plasma during the treatment. And through the AFM analysis it was possible to observe the changes nanotopography occurred on the surface of the samples. Permeability assay were archived for all treated membranes and compared to no treated ones. Due to that assay it was possible verify which the plasma treatment increased the permeability spectrum of the membranes which has varied from 1,4548 *10-5cm2.min-1 to 2,7713*10-5cm2.min-1. Chitosan membranes with permeability varied are importance in systems drug delivery, to liberate a wide variety of drugs

Síntese e caracterização do poli(ácido láctico) para potencial uso em sistemas de liberação controlada de fármacos

With the advances in medicine, life expectancy of the world population has grown considerably in recent decades. Studies have been performed in order to maintain the quality of life through the development of new drugs and new surgical procedures. Biomaterials is an example of the researches to improve quality of life, and its use goes from the reconstruction of tissues and organs affected by diseases or other types of failure, to use in drug delivery system able to prolong the drug in the body and increase its bioavailability. Biopolymers are a class of biomaterials widely targeted by researchers since they have ideal properties for biomedical applications, such as high biocompatibility and biodegradability. Poly (lactic acid) (PLA) is a biopolymer used as a biomaterial and its monomer, lactic acid, is eliminated by the Krebs Cycle (citric acid cycle). It is possible to synthesize PLA through various synthesis routes, however, the direct polycondensation is cheaper due the use of few steps of polymerization. In this work we used experimental design (DOE) to produce PLAs with different molecular weight from the direct polycondensation of lactic acid, with characteristics suitable for use in drug delivery system (DDS). Through the experimental design it was noted that the time of esterification, in the direct polycondensation, is the most important stage to obtain a higher molecular weight. The Fourier Transform Infrared (FTIR) spectrograms obtained were equivalent to the PLAs available in the literature. Results of Differential Scanning Calorimetry (DSC) showed that all PLAs produced are semicrystalline with glass transition temperatures (Tgs) ranging between 36 - 48 °C, and melting temperatures (Tm) ranging from 117 to 130 °C. The PLAs molecular weight characterized from Size Exclusion Chromatography (SEC), varied from 1000 to 11,000 g/mol. PLAs obtained showed a fibrous morphology characterized by Scanning Electron Microscopy (SEM)

Desenvolvimento de uma formulação cólon específica visando o tratamento da colite ulcerativa

Micro and nanoparticulate systems as drug delivery carriers have achieved successful therapeutic use by enhancing efficacy and reducing toxicity of potent drugs. The improvement of pharmaceutical grade polymers has allowed the development of such therapeutic systems. Microencapsulation is a process in which very thin coatings of inert natural or synthetic polymeric materials are deposited around microsized particles of solids or around droplets. Products thus formed are known as microparticles. Xylan is a natural polymer abundantly found in nature. It is the most common hemicellulose, representing more than 60% of the polysaccharides existing in the cell walls of corn cobs, and is normally degraded by the bacterial enzymes present in the colon of the human body. Therefore, this polymer is an eligible material to produce colon-specific drug carriers. The aim of this study was to evaluate the technological potential of xylan for the development of colon delivery systems for the treatment of inflammatory bowel diseases. First, coacervation was evaluated as a feasible method to produce xylan microcapsules. Afterwards, interfacial cross-linking polymerization was studied as a method to produce microcapsules with hydrophilic core. Additionally, magnetic xylan-coated microcapsules were prepared in order to investigate the ability of producing gastroresistant systems. Besides, the influence of the external phase composition on the production and mean diameter of microcapsules produced by interfacial cross-linking polymerization was investigated. Also, technological properties of xylan were determined in order to predict its possible application in other pharmaceutical dosage forms