Nanotechnology-based drug delivery systems for melanoma antitumoral therapy: a review

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Polyacrylic acid polymers hydrogels intended to topical drug delivery: preparation and characterization

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Relationship between composition and organizational levels of nanostructured systems formed by Oleth 10 and PPG-5-Ceteth-20 for potential drug delivery

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

Nanotechnology-based drug delivery systems for the treatment of Alzheimer's disease

Alzheimer's disease is a neurological disorder that results in cognitive and behavioral impairment. Conventional treatment strategies, such as acetylcholinesterase inhibitor drugs, often fail due to their poor solubility, lower bioavailability, and ineffective ability to cross the blood-brain barrier. Nanotechnological treatment methods, which involve the design, characterization, production, and application of nanoscale drug delivery systems, have been employed to optimize therapeutics. These nanotechnologies include polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, and liquid crystals. Each of these are promising tools for the delivery of therapeutic devices to the brain via various routes of administration, particularly the intranasal route. The objective of this study is to present a systematic review of nanotechnology-based drug delivery systems for the treatment of Alzheimer's disease.

Dendrimers as potential platform in nanotechnology-based drug delivery systems

The dendrimers of poly (amidoamine) (PAMAM) are nanoparticles which have proven succeed in transporting drugs due to high solubility, low toxicity and ability to control drugs release. Studies have explored the biological potential of dendrimers such as to transport genes, development of vaccines, antiviral, antibacterial and anticancer therapies. This review of literature on the PAMAM dendrimers discusses the architecture and general construction of dendrimers and intrinsic properties of the PAMAM. This study also describes how the PAMAM interact with many drugs and the potential of these macromolecules as well as drug nanocarriers in transdermal routes of administration, ocular, respiratory, oral and intravenous administration. Dendrimers promises good future prospects for the biomedicine.

Development and characterization of biocompatible isotropic and anisotropic oil-in-water colloidal dispersions as a new delivery system for methyl dihydrojasmonate antitumor drug

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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)

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.