Water-soluble Polyester-based Amino Acids-modified Dendrimers loaded with Ursolic and Oleanolic Acids as promising Prodrugs suitable for Intravenous Administration

Dendrimers, macromolecules characterized by high controlled size, shape and architecture, presence of inner cavities able to accommodate small molecules and many peripheral functional groups, are of eminent interest for biomedical applications, including gene transfection, tissue engineering, imaging, drug delivery.[1] The well-known pharmacological activities of Ursolic and Oleanolic acids[2] are limited by low water solubility, non-specific cells distribution, poor bioavailability and pharmacokinetics. Thus, the research for new formulations of UA and OA that overcome such drawbacks is very extensive. The strategy most applied concerns the use of carriers, such as liposomes or PAMAM dendrimers which are among the most investigated vectors because endowed with very efficient transfection and delivery activities but also with remarkable cytotoxicity. In this work we described the physical incorporation of the two triterpene acids extracted from Salvia Corrugata inside amino acids-modified polyester-based dendrimers.[3,4] IR, NMR, zeta potential, mean size of particles and buffer capacity of prepared materials were reported. Figure 1. An eye-catching representation of the prepared complexes The achieved water soluble complexes harmonize a polycationic character and a buffer capacity which presuppose efficient cells penetration and increased residence time with a biodegradable scaffold thus appearing as a promising team of new non-toxic prodrugs for safe intravenous administration of Ursolic and Oleanolic acids (Figure 1). [1] S. N. Goonewardena, J. D. Kratz, H. Zong, A. M. Desai, S. Tang, S. Emery, J. R. Jr. Baker, B. Huang, Design considerations for PAMAM dendrimer therapeutics, Biorg. Med. Chem. lett., 23, 2872 (2013). [2] J. Liu, Pharmacology of oleanolic acid and ursolic acid, J. Ethnopharmacol., 49, 57 (1995). [3] S. Alfei, S. Castellaro, Synthesis and Characterization of Polyester-Based Dendrimers Containing Peripheral Arginine or Mixed Amino Acids as Potential Vectors for Gene and Drug Delivery, Macromol. Res., DOI 10.1007/s13233-017-5160-3 (2017). [4] S. Alfei, S. Castellaro, G. B. Taptue, Synthesis and NMR characterization of dendrimers based on 2, 2-bis-(hydroxymethyl)-propanoic acid (bis-HMPA) containing peripheral amino acid residues for gene transfection, Org. Commun., 10, 144 (2017).