Dressing liposomal particles with chitosan and poly(vinylic alcohol) for oral vaccine delivery

Liposomes have been used as adjuvants since 1974. One major limitation for the use of liposomes in oral vaccines is the lipid structure instability caused by enzyme activities. Our aim was to combine liposomes that could encapsulate antigens (i.e., Dtxd, diphtheria toxoid) with chitosan, which protects the particles and promotes mucoadhesibility. We employed physical techniques to understand the process by which liposomes (SPC: Cho, 3: 1) can be sandwiched with chitosan (Chi) and stabilized by PVA (poly-vinylic alcohol), which are biodegradable, biocompatible polymers. Round, smooth-surfaced particles of REVs-Chi (reversed-phase vesicles sandwiched by Chi) stabilized by PVA were obtained. The REVs encapsulation efficiencies (Dtxd was used as the antigen) were directly dependent on the Chi and PVA present in the formulation. Chi adsorption on the REVs surface was accompanied by an increase of zeta-potential. In contrast, PVA adsorption on the REVs-Chi surface was accompanied by a decrease of zeta-potential. The presence of Dtxd increased the Chi surface-adsorption efficiency. The PVA affinity by mucine was 2,000 times higher than that observed with Chi alone and did not depend on the molecule being in solution or adsorbed on the liposomal surface. The liberation of encapsulated Dtxd was retarded by encapsulation within REVs-Chi-PVA. These results lead us to conclude that these new, stabilized particles were able to be adsorbed by intestinal surfaces, resisted degradation, and controlled antigen release. Therefore, REVs-Chi-PVA particles can be used as an oral delivery adjuvant.

Preparation and characterisation of Dextran-70 hydrogel for controlled release of praziquantel

Um hidrogel foi desenvolvido a partir de dextrano 70 kDa (DEX-70) e praziquantel incorporado (PZQ) como fármaco modelo. Propriedades biofarmacêuticas, como solubilidade e velocidade de dissolução, foram analisadas no desenvolvimento do hidrogel. Além disso, o hidrogel também foi caracterizado por espectroscopia na região do infravermelho e calorimetria diferencial exploratória (DSC). Testes da taxa de intumescimento mostraram que o hidrogel intumesce lentamente, embora tenha sido mais rápido do que a taxa do polímero livre. Nos testes de dissolução, o hidrogel liberou o fármaco lenta e continuamente. Esta liberação lenta foi semelhante a observada nos testes de intumescimento e resultou em uma liberação controlada do fármaco. Assim, o dextrano 70 kDa é um polímero adequado para o desenvolvimento de hidrogéis como veículos para a liberação controlada de fármacos.

In vitro drug permeation from chitosan pellets

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Controlled Drug Release from Ureasil-Polyether Hybrid Materials

Flexible, transparent, and insoluble urea-cross-linked polyether-siloxane hybrids presenting a tunable drug delivery pattern were prepared using the sol-gel method from PEO (poly(ethylene oxide)) and PPO (poly(propylene oxide)) functionalized at both chain ends with triethoxysilane. Different polyether chain lengths were used to control the urea/siloxane (named ureasil) node density, flexibility, and swellability of the hybrid network. We herein demonstrate that the drug release from swellable hydrophilic ureasil-PEO hybrids can be sustained for some days, whereas that from the unswellable ureasil-PPO hybrids can be sustained for some weeks. This outstanding feature conjugated with the biomedically safe formulation of the ureasil cross-linked polyether-siloxane hybrid widens their scope of application to include the domain of soft and implantable drug delivery devices.

Evaluation of chitosan gel as antibiotic and photosensitizer delivery

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Biocompatibility of a chlorhexidine local delivery system in a subcutaneous mouse model

Objective: This study aimed evaluating histologically and histomorphometrically the response of the conjunctive tissue face to the implant of chlorhexidine chips in the subcutaneous tissues of rats. Study Design: In this research 35 male rats Wistar were used to analyze the biocompatibility and the degradation process of chlorhexidine chip. In each animal, it was made 2 incisions for subcutaneous implantation of chlorhexidine chip (test group) and a polytetrafluorethylene membrane (control group). The morphological changes in subcutaneous implantations were assessed after 1, 3, 5, 7, 10, 14, 21 days. The data were submitted to Friedman nonparametric test to analyze the comparisons among observation periods and to allow the comparison among groups. Results: Differences were found in the analysis of the inflammatory response when comparing the tested materials (p values <= 0.05). In test group was observed hemorrhage, edema and intense inflammatory infiltrate predominantly neutrophilic around material. From 3-day and subsequent periods was verified granulation tissue externally at this infiltrate. From 10-day on was observed crescent area of degradation of chlorhexidine chip, associated with neutrophilic and macrophagic infiltrate, that maintained until 21-day. In the control group, moderate inflammatory infiltrate was observed initially, predominantly polymorphonuclear, edema and granulation tissue 3-day period. The inflammatory infiltrate was gradually replaced for granulation tissue, culminating in a fibrous capsule. Giant multinucleate cells situated at contact interface with the coating was examined since 3-day and persisted until 21-day. Conclusion: The chlorhexidine chip induces an intense acute inflammatory response at subcutaneous tissue of rats. Therefore, at conditions of this study was not biocompatible.

Multi-spectroscopic monitoring of cisplatin-derived species delivery from ureasil polyether hybrid matrix

Driven by the challenges involved in the development of new advanced materials with unusual drug delivery profiles capable of improving the therapeutic and toxicological properties of existing cancer chemotherapy, the one-pot sol-gel synthesis of flexible, transparent and insoluble urea-cross-linked polyether-siloxane hybrids has been recently developed. In this one-pot synthesis, the strong interaction between the antitumor cisplatin (CisPt) molecules and the ureasil-poly(propylene oxide) (PPO) hybrid matrix gives rise to the incorporation and release of an unknown CisPt-derived species, hindering the quantitative determination of the drug release pattern from the conventional UV-Vis absorption technique. In this article, we report the use of an original synchrotron radiation calibration method based on the combination of XAS and UV-Vis for the quantitative determination of the amount of Pt-based molecules released in water. Thanks to the combination of UV-Vis, XAS and Raman techniques, we demonstrated that both the CisPt molecules and the CisPt-derived species are loaded into an ureasil-PPO/ureasil-poly(ethylene oxide) (PEO) hybrid blend matrix. The experimentally determined molar extinction coefficient of the CisPt-derived species loaded into ureasil-PPO hybrid matrix enabled the simultaneous time-resolved monitoring of each Pt species released from this hybrid blend matrix.

Oil-in-water lecithin-based microemulsions as a potential delivery system for amphotericin B

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Characterization of PLGA microparticles as a drug carrier for 3-ethoxycarbonyl-2H-benzofuro[3,2-f]-1-benzopyran-2-one. Ultrastructural study of cellular uptake and intracellular distribution

Here we describe the application of microparticles (MPs) for the delivery and release of the drug a benzopsoralen. We also evaluated the intracellular distribution and cellular uptake of the drug by using an encapsulation technique for therapeutic optimization. MPs containing the compound 3-ethoxycarbonyl-2H-benzofuro[3,2-f]-1-benzopyran-2-one (psoralen A) were prepared by the solvent evaporation technique, and parameters such as particle size, drug encapsulation efficiency, effect of the encapsulation process on the drug's photochemistry, zeta potential, external morphology, and < i > in vitro release behavior were evaluated. The intracellular distribution of MPs as well as their uptake by tissues were monitored. Size distribution studies using dynamic ligh scattering and scanning electron microscopy revealed that the MPs are spherical in shape with a diameter of 1.4 mu m. They present low tendency toward aggregation, as confirmed by their zeta potential (+10.6 mV). The loading efficiency obtained was 75%. As a consequence of the extremely low diffusivity of the drug in aqueous medium, the drug release profile of the MPs in saline phosphate buffer (pH 7.4) was much slower than that obtained in the biological environment. Among the population of peritoneal phagocytic cells, only macrophages were able to phagocytose poly-d,l-lactic-co-glycolic acid (PLGA) MP. The use of psoralen A in association with ultraviolet light (360 nm) revealed morphological characteristics of cell damage such as cytoplasmic vesiculation, mitochondria condensation, and swelling of both the granular endoplasmatic reticulum and the nuclear membrane. These results indicate that PLGA MP could be a promising delivery system for psoralen in connection with ultraviolet irradiation therapy (PUVA).

Drug-matrix interaction of sodium diclofenac incorporated into ureasilpoly(ethylene oxide) hybrid materials

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo quantitativo da lágrima pelo teste de fenol vermelho na população brasileira

Purpose: To detect normal values of red phenol thread test in the Brazilian population and compare it between different races, age and sex. Methods: 280 white individuals (560 eyes) and 280 non-white individuals (560 eyes) were analyzed regarding sex and age, and analyzed using the Phenol Red test. Individuals with ocular diseases, contact lens or ocular drug users were excluded from this study. Results: Of the 1,120 evaluated eyes, the mean ± standard deviation result was 19,77±7,90 mm. Conclusion: The mean result found in this study was an intermediate value compared to the previously studied populations (Japanese and American).

Chorismate synthase: An attractive target for drug development against orphan diseases

The increase in incidence of infectious diseases worldwide, particularly in developing countries, is worrying. Each year, 14 million people are killed by infectious diseases, mainly HIV/AIDS, respiratory infections, malaria and tuberculosis. Despite the great burden in the poor countries, drug discovery to treat tropical diseases has come to a standstill. There is no interest by the pharmaceutical industry in drug development against the major diseases of the poor countries, since the financial return cannot be guaranteed. This has created an urgent need for new therapeutics to neglected diseases. A possible approach has been the exploitation of the inhibition of unique targets, vital to the pathogen such as the shikimate pathway enzymes, which are present in bacteria, fungi and apicomplexan parasites but are absent in mammals. The chorismate synthase (CS) catalyses the seventh step in this pathway, the conversion of 5-enolpyruvylshikimate-3-phosphate to chorismate. The strict requirement for a reduced flavin mononucleotide and the anti 1,4 elimination are both unusual aspects which make CS reaction unique among flavin-dependent enzymes, representing an important target for the chemotherapeutic agents development. In this review we present the main biochemical features of CS from bacterial and fungal sources and their difference from the apicomplexan CS. The CS mechanisms proposed are discussed and compared with structural data. The CS structures of some organisms are compared and their distinct features analyzed. Some known CS inhibitors are presented and the main characteristics are discussed. The structural and kinetics data reviewed here can be useful for the design of inhibitors. © 2007 Bentham Science Publishers Ltd.

Magnetic multiparticulate colonic delivery systems evaluated by AC Biosusceptometry

The biomagnetic technique called Alternate Current Biosusceptometry (ACB) is a proposal to evaluate a multiparticulate drug delivery system in the human gastrointestinal tract. Results show that ACB was able to quantify the gastrointestinal transit and spreading of the magnetic material and is an attractive tool for pharmaceutical research. © 2007.

Desenvolvimento de blendas de dextranos de pesos moleculares 70 e 148 KDA para a obtenção de hidrogéis contendo praziquantel

Pós-graduação em Ciências Farmacêuticas - FCFAR

Modificação da superfície de óxidos de ferro por dextrana derivatizada para aplicações em liberação de fármaco

Pós-graduação em Química - IQ