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- Principal physicochemical methods used to characterize dendrimer molecule complexes used as genetic therapy agents, nanovaccines or drug carriersPublication . Rolando Alberto, Rodriguez Fonseca; Rodrigues, João; Muñoz-Fernández, María de los Angeles; Martínez Muñoz, Alberto; Fragoso Vázquez, Manuel Jonathan; Correa-Basurto, JoséNanomedicine is the application of nanotechnology to medicine. This field is related to the study of nanodevices and nanomaterials applied to various medical uses, such as in improving the pharmacological properties of different molecules. Dendrimers are synthetic nanoparticles whose physicochemical properties vary according to their chemical structure. These molecules have been extensively investigated as drug nanocarriers to improve drug solubility and as sustained-release systems. New therapies such as gene therapy and the development of nanovaccines can be improved by the use of dendrimers. The biophysical and physicochemical characterization of nucleic acid/peptide-dendrimer complexes is crucial to identify their functional properties prior to biological evaluation. In that sense, it is necessary to first identify whether the peptide-dendrimer or nucleic aciddendrimer complexes can be formed and whether the complex can dissociate under the appropriate conditions at the target cells. In addition, biophysical and physicochemical characterization is required to determine how long the complexes remain stable, what proportion of peptide or nucleic acid is required to form the complex or saturate the dendrimer, and the size of the complex formed. In this review, we present the latest information on characterization systems for dendrimer-nucleic acid, dendrimer-peptide and dendrimer-drug complexes with several biotechnological and pharmacological applications.
- Dendrimers toward translational nanotherapeutics: concise key step analysisPublication . Mignani, Serge; Shi, Xiangyang; Rodrigues, João; Roy, René; Muñoz-Fernández, Ángeles; Ceña, Valentin; Majoral, Jean PierreThe goal of nanomedicine is to address specific clinical problems optimally, to fight human diseases, and to find clinical relevance to change clinical practice. Nanomedicine is poised to revolutionize medicine via the development of more precise diagnostic and therapeutic tools. The field of nanomedicine encompasses numerous features and therapeutic disciplines. A plethora of nanomolecular structures have been engineered and developed for therapeutic applications based on their multitasking abilities and the wide functionalization of their core scaffolds and surface groups. Within nanoparticles used for nanomedicine, dendrimers as well polymers have demonstrated strong potential as nanocarriers, therapeutic agents, and imaging contrast agents. In this review, we present and discuss the different criteria and parameters to be addressed to prepare and develop druggable nanoparticles in general and dendrimers in particular. We also describe the major requirements, included in the preclinical and clinical roadmap, for NPs/dendrimers for the preclinical stage to commercialization. Ultimately, we raise the clinical translation of new nanomedicine issues.
- New anionic poly(alkylideneamine) dendrimers as microbicide agents against HIV-1 infectionPublication . Maciel, Dina; Guerrero-Beltrán, Carlos; Ceña-Diez, Rafael; Tomás, Helena; Muñoz-Fernández, M. Ángeles; Rodrigues, JoãoAcquired immune deficiency syndrome (AIDS) due to human immunodeficiency virus type-1 (HIV-1) represents one of the most important sexually transmitted infections (STI) worldwide. Great international efforts have been made to stop new infections but, to date, several compounds failed as microbicides at different stages of clinical trials. The quest to design new molecules that could prevent these infections is essential. In this work, we synthesized the first, second and third generations of anionic dendrimers having carboxylate and sulfonate terminal groups, respectively named G1C, G2C, G3C and G1S, G2S, and G3S, starting from a family of poly(alkylideneamine) dendrimers with nitrile termini. The anionic terminal groups of these dendrimers were expected to prompt them to act against HIV-1 infection. All dendrimers were fully characterized by 1H- and 13C-NMR, FTIR, MS and zeta potential techniques. Importantly, they were able to remain stable in the solid state and aqueous solutions at least for one and a half years. Screening of these six new dendrimers was then performed to shed light on their potential anti-HIV-1 activity and their mechanism of action. Results showed that the dendrimers were cytocompatible and that G1C and G1S dendrimers had important activity against R5-HIV-1NLAD8 and X4-HIV-1NL4.3 isolates by acting directly on viral particles and blocking their entry in host cells. Additionally, G1C and G1S dendrimers maintained their inhibitory effect at different pH values. Through a vaginal irritation assay carried out in BALB/c mice, the safety of these new dendrimers for topical application was also shown. Taken together, our results clearly show that G1C and G1S dendrimers are strong candidates for developing an effective microbicide to prevent HIV-1 new infections.