Ursolic acid (UA) is a pentacyclic triterpenoid found in many medicinal plants and aromas endowed with numerous in vitro pharmacological activities, including antibacterial effects. Unfortunately, UA is poorly administered in vivo, due to its water insolubility, low bioavailability, and residual systemic toxicity, thus making urgent the development of water-soluble UA formulations. Dendrimers are nonpareil macromolecules possessing highly controlled size, shape, and architecture. In dendrimers with cationic surface, the contemporary presence of inner cavities and of hydrophilic peripheral functions, allows to encapsulate hydrophobic non-water-soluble drugs as UA, to enhance their water-solubility and stability, and to promote their protracted release, thus decreasing their systemic toxicity. In this paper, aiming at developing a new UA-based antibacterial agent administrable in vivo, we reported the physical entrapment of UA in a biodegradable not cytotoxic cationic dendrimer (G4K). UA-loaded dendrimer nanoparticles (UA-G4K) were obtained, which showed a drug loading (DL%) much higher than those previously reported, a protracted release profile governed by diffusion mechanisms, and no cytotoxicity. Also, UA-G4K was characterized by principal components analysis (PCA)-processed FTIR spectroscopy, by NMR and elemental analyses, and by dynamic light scattering experiments (DLS). The water solubility of UA-G4K was found to be 1868-fold times higher than that of pristine UA, thus making its clinical application feasible.

Considerable Improvement of Ursolic Acid Water Solubility by Its Encapsulation in Dendrimer Nanoparticles: Design, Synthesis and Physicochemical Characterization

Alfei, Silvana;Schito, Anna Maria;Zuccari, Guendalina
2021-01-01

Abstract

Ursolic acid (UA) is a pentacyclic triterpenoid found in many medicinal plants and aromas endowed with numerous in vitro pharmacological activities, including antibacterial effects. Unfortunately, UA is poorly administered in vivo, due to its water insolubility, low bioavailability, and residual systemic toxicity, thus making urgent the development of water-soluble UA formulations. Dendrimers are nonpareil macromolecules possessing highly controlled size, shape, and architecture. In dendrimers with cationic surface, the contemporary presence of inner cavities and of hydrophilic peripheral functions, allows to encapsulate hydrophobic non-water-soluble drugs as UA, to enhance their water-solubility and stability, and to promote their protracted release, thus decreasing their systemic toxicity. In this paper, aiming at developing a new UA-based antibacterial agent administrable in vivo, we reported the physical entrapment of UA in a biodegradable not cytotoxic cationic dendrimer (G4K). UA-loaded dendrimer nanoparticles (UA-G4K) were obtained, which showed a drug loading (DL%) much higher than those previously reported, a protracted release profile governed by diffusion mechanisms, and no cytotoxicity. Also, UA-G4K was characterized by principal components analysis (PCA)-processed FTIR spectroscopy, by NMR and elemental analyses, and by dynamic light scattering experiments (DLS). The water solubility of UA-G4K was found to be 1868-fold times higher than that of pristine UA, thus making its clinical application feasible.
File in questo prodotto:
File Dimensione Formato  
nanomaterials-11-02196-v2.pdf

accesso aperto

Descrizione: Articolo Completo
Tipologia: Documento in versione editoriale
Dimensione 7.39 MB
Formato Adobe PDF
7.39 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/1054713
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 22
  • ???jsp.display-item.citation.isi??? 19
social impact