Desenvolvimento de sistemas magnéticos com potencialidades terapêuticas para vetorização de fármacos

Magnetic targeting is being investigated as a means of local delivery of drugs, combining precision, minimal surgical intervention, and satisfactory concentration of the drug in the target region. In view of these advantages, it is a promising strategy for improving the pharmacological response. Magnetic particles are attracted by a magnetic field gradient, and drugs bound to them can be driven to their site of action by means of the selective application of magnetic field on the desired area. Helicobacter pylori is the commonest chronic bacterial infection. The treatment of choice has commonly been based upon a triple therapy combining two antibiotics and an anti-secretory agent. Furthermore, an extended-release profile is of utmost importance for these formulations. The aim of this work was to develop a magnetic system containing the antibiotic amoxicillin for oral magnetic drug targeting. First, magnetic particles were produced by coprecipitation of iron salts in alkaline medium. The second step was coating the particles and amoxicillin with Eudragit® S-100 by spray-drying technique. The system obtained demonstrated through the characterization studies carried out a possible oral drug delivery system, consisting in magnetite microparticles and amoxicillin, coated with a polymer acid resistant. This system can be used to deliver drugs to the stomach for treatment of infections in this organ. Another important finding in this work is that it opens new prospects to coat magnetic microparticles by the technique of spray-drying.

Micropartículas de poli (ácido láctico)/ poloxámero obtids por spray drying para liberação modificada de metotrexatro

New drug delivery systems have been used to increase chemotherapy efficacy due the possible drug resistance of cancer cells. Poly (lactic acid) (PLA) microparticles are able to reduce toxicity and prolong methotrexate (MTX) release. In addition, the use of PLA/poloxamer polymer blends can improve drug release due to changes in the interaction of particles with biological surfaces. The aim of this study was developing spray dried biodegradable MTX-loaded microparticles and evaluate PLA interactions with different kinds of Pluronic® (PLUF127 and PLUF68) in order to modulate drug release. The variables included different drug:polymer (1:10, 1:4.5, 1:3) and polymer:copolymer ratios (25:75, 50:50, 75:25). The precision and accuracy of spray drying method was confirmed assessing drug loading into particles (75.0- 101.3%). The MTX/PLA microparticles showed spherical shape with an apparently smooth surface, which was dependent on the PLU ratio used into blends particles. XRD and thermal analysis demonstrated that the drug was homogeneously dispersed into polymer matrix, whereas the miscibility among components was dependent on the used polymer:copolymer ratio. No new drug- polymer bond was identified by FTIR analysis. The in vitro performance of MTX-loaded PLA microparticles demonstrated an extended-release profile fitted using Korsmeyer- Peppas kinetic model. The PLU accelerated drug release rate possible due PLU leached in the matrix. Nevertheless, drug release studies carried out in cell culture demonstrated the ability of PLU modulating drug release from blend microparticles. This effect was confirmed by cytotoxicity observed according to the amount of drug released as a function of time. Thus, studied PLU was able to improve the performance of spray dried MTX-loaded PLA microparticles, which can be successfully used as carries for modulated drug delivery with potential in vivo application

Obtenção e caracterização de sistemas particulados de quitosana para liberação gástrica de amoxicilina

The infection caused by Helicobacter pylori (H. pylori) is associated with gastroduodenal inflammation can lead to the development of gastritis, gastric or duodenal ulcer and gastric cancer (type 1 carcinogen for stomach cancer). Amoxicillin is used as first-line therapy in the treatment of H. pylori associated to metronidazole or clarithromycin, and a proton pump inhibitor. However, the scheme is not fully effective due to inadequate accumulation of antibiotics in gastric tissue, inadequate efficacy of ecological niche of H. pylori, and other factors. In this context, this study aimed to obtaining and characterization of particulate systems gastrorretentivos chitosan - amoxicillin aiming its use for treatment of H. pylori infections. The particles were obtained by the coacervation method / precipitation using sodium sulfate as precipitating agent and crosslinking and two techniques: addition of amoxicillin during preparation in a single step and the sorption particles prior to amoxycillin prepared by coacervation / precipitation and spray drying. The physicochemical characterization of the particles was performed by SEM, FTIR, DSC, TG and XRD. The in vitro release profile of amoxycillin free and incorporated in the particles was obtained in 0.1 N HCl (pH = 1.2). The particles have higher encapsulation efficiency to 80% spherical shape with interconnected particles or adhered to each other, the nanometric diameter to the systems obtained by coacervation / precipitation and fine for the particles obtained by spray drying. The characterization by FTIR, DSC and XRD showed that the drug was incorporated into the nanoparticles dispersed in the polymeric matrix. Thermal analysis (TG and DSC) indicated that encapsulation provides greater heat stability to the drug. Amoxicillin encapsulated in nanoparticles had slower release compared to free drug. The particles showed release profile with a faster initial stage (burst effect) reaching a maximum at 30 minutes 35% of amoxicillin for the system in 1: 1 ratio relative to the polymer and 80% for the system in the ratio 2: 1. Although simple and provide high encapsulation efficiency of amoxicillin, the process of coacervation, precipitation in one step using sodium sulfate as precipitant / cross-linker must be optimized in order to adjust the release kinetics according to the intended application.

Nanopartículas catiônicas de poli (ácido lático) para liberação modificada de peptídios da peçonha do escorpião Tityus serrulatus

Reported accidents involving the poisoning scorpions are still frequent in Brazil, mainly caused by Tityus serrulatus, known as yellow scorpion. Although antivenom sera are produced routinely by various government laboratories, the effectiveness of its use depends on how quickly treatment is initiated and efficiency in the production of antibodies by the immunized animals. In this study, the development of cationic polymeric nanoparticles of poly(lactic acid) aimed to create a modified delivery system for peptides and proteins of T. serrulatus venom, able to enhance the production of serum antibodies against the scorpion toxins. The cationic nanoparticles were obtained by a low energy nanoprecipitation, after study of the parameters’ variations effects over the physicochemical properties of the particles. The surface functionalization of the nanoparticles with the hyperbranched polyethyleneimine was proved by zeta potential analysis and enabled the adsorption by electrostatic interaction of different types of proteins. The protein loading efficiency of 40-80 % to bovine serum albumin (BSA) and 100 % to scorpion venom peptides evaluated by spectrophotometry and polyacrylamide gel electrophoresis confirmed the success of the selected parameters established for obtainment of nanoparticles, produced with size between 100 to 250 nm. The atomic force microscopy analysis and in vitro release showed that the spherical nanoparticles provided a sustained release profile of proteins by diffusion mechanism, demonstrating the potential for application of the nanoparticles in vivo.

Nanopartículas catiônicas de poli (ácido lático) para liberação modificada de peptídios da peçonha do escorpião Tityus serrulatus

Reported accidents involving the poisoning scorpions are still frequent in Brazil, mainly caused by Tityus serrulatus, known as yellow scorpion. Although antivenom sera are produced routinely by various government laboratories, the effectiveness of its use depends on how quickly treatment is initiated and efficiency in the production of antibodies by the immunized animals. In this study, the development of cationic polymeric nanoparticles of poly(lactic acid) aimed to create a modified delivery system for peptides and proteins of T. serrulatus venom, able to enhance the production of serum antibodies against the scorpion toxins. The cationic nanoparticles were obtained by a low energy nanoprecipitation, after study of the parameters’ variations effects over the physicochemical properties of the particles. The surface functionalization of the nanoparticles with the hyperbranched polyethyleneimine was proved by zeta potential analysis and enabled the adsorption by electrostatic interaction of different types of proteins. The protein loading efficiency of 40-80 % to bovine serum albumin (BSA) and 100 % to scorpion venom peptides evaluated by spectrophotometry and polyacrylamide gel electrophoresis confirmed the success of the selected parameters established for obtainment of nanoparticles, produced with size between 100 to 250 nm. The atomic force microscopy analysis and in vitro release showed that the spherical nanoparticles provided a sustained release profile of proteins by diffusion mechanism, demonstrating the potential for application of the nanoparticles in vivo.