Nanosystems for gene therapy targeting brain damage caused by viral infections.

Several human pathogens can cause long-lasting neurological damage. Despite the increasing clinical knowledge about these conditions, most still lack efficient therapeutic interventions. Gene therapy (GT) approaches comprise strategies to modify or adjust the expression or function of a gene, thus providing therapy for human diseases. Since recombinant nucleic acids used in GT have physicochemical limitations and can fail to reach the desired tissue, viral and non-viral vectors are applied to mediate gene delivery. Although viral vectors are associated to high levels of transfection, non-viral vectors are safer and have been further explored. Different types of nanosystems consisting of lipids, polymeric and inorganic materials are applied as non-viral vectors. In this review, we discuss potential targets for GT intervention in order to prevent neurological damage associated to infectious diseases as well as the role of nanosized non-viral vectors as agents to help the selective delivery of these gene-modifying molecules. Application of non-viral vectors for delivery of GT effectors comprise a promising alternative to treat brain inflammation induced by viral infections.

Therapeutic nanosystems for oral administration of insulin.

The treatment of Diabetes Mellitus (DM), a chronic disease, is primarily based upon administration of insulin forms to patients. Conventional subcutaneous administration is associated with a large number of complications, therefore, several new strategies have been developed. Amongst these strategies, oral insulin administration is much less invasive and, therefore, well tolerated. In recent years, various nanoformulations were developed for the oral administration of insulin, allowing more effective stabilization of the active pharmaceutical ingredient and modified for better absorption along the gastrointestinal tract. The development of different oral insulin nanoformulations in academic research as well as in patents, including the development of nanoparticles, liposomes, nanoemulsions and the use of cyclodextrins deserves special attention. The future of oral insulin nanoformulations is dependent on strategies utilizing simple technologies that stabilize the raw material, including inclusion within cyclodextrins or inclusion in low weight molecular mass polymers/ oligomers. All of the theories developed here provide a solid foundation upon which to develop new methods for the production of pharmaceutical peptide formulations. In addition, the effective search for existing nanometric formulations of insulin could provide economically viable therapeutic options that can consequently be produced on an industrial scale.

Development and characterization of a new oral dapsone nanoemulsion system: permeability and in silico bioavailability studies.

BACKGROUND: Dapsone is described as being active against Mycobacterium leprae, hence its role in the treatment of leprosy and related pathologies. Despite its therapeutic potential, the low solubility of dapsone in water results in low bioavailability and high microbial resistance. Nanoemulsions are pharmaceutical delivery systems derived from micellar solutions with a good capacity for improving absorption. The aim of this work was to develop and compare the permeability of a series of dapsone nanoemulsions in Caco-2 cell culture against that of effective permeability in the human body simulated using Gastroplus™ software. METHODS AND RESULTS: The release profiles of the dapsone nanoemulsions using different combinations of surfactants and cosolvent showed a higher dissolution rate in simulated gastric and enteric fluid than did the dispersed dapsone powder. The drug release kinetics were consistent with a Higuchi model. CONCLUSION: This comparison of dapsone permeability in Caco-2 cells with effective permeability in the human body simulated by Gastroplus showed a good correlation and indicates potential improvement in the biodisponibility of dapsone using this new system.