Characterization of water soluble dendrimer formulations of an insoluble thiocarbamate derivative with moderate anti HIV-1 activity: an overview

Drug delivery is an engineered technology focused on the development of Drug Delivery Systems (DDSs) able to transport, release and maintain for long time the useful load of therapeutics in the body as needed for safe playing out the desired therapeutic effects. Nanosized dendritic polycationic polymers such as commercially available PAMAMs, are the most exploited materials for preparing smart DDSs, but unfortunately, the excessive cationic feature of the inner framework results in a high level of cytotoxicity. Nowadays, not charged amino acid-modified dendrimer scaffolds are considered as better solutions. These dendrimers have a more controlled number of nitrogen atoms and can be protonated at physiological pH. In order to improve the water solubility of the thiocarbamate non-nucleoside HIV-1 reverse transcriptase inhibitor 1 (Figure 1)1 five prodrugs were prepared by its entrapment inside not PAMAM amino acids-modified core-shell hydrophilic2 (Figure 2) and amphiphilic3 (Figure 3) dendrimers. As detailed in this communication an overview, organized in tables, graphs and NMR spectra of the physicochemical properties which identified obtained dendriplexes (DPXs) was provided. As estimated by NMR analysis, DPXs showed good load capacity. Mean size of their particles is suitable for avoiding rapid renal clearance while the release profile of the drug is favourable to a low spreading of drug in blood and to a massive release only within the cell. DPXs are soluble in water, EtOH and MeOH, have proper but not excessive cationic character and an optimal buffer capacity for enhanced cellular up take and pH-responsive endosomal escape once inside the cell. References: [1] A. Spallarossa, A. Ranise, et al., Eur. J. Med. Chem. 2009, 44, 1650-1663. [2] S. Alfei, S. Catena, 2018, submitted to Polym. Advan. Technol. 2018: https://doi.org/10.1002/pat.4396. [3] S. Alfei, S. Catena, 2018, submitted to Polym. Int. 2018, https://doi.org: 10.1002/pi.5680.