Ellagitannins (ETs) and Ellagic acid (EA) (Fig.1) are bioactive polyphenols naturally present in numerous berries and nuts (i.e. pomegranates, black raspberries, raspberries, strawberries, walnuts almonds) and are endowed with antioxidant, anticancer, anti-inflammatory, antimicrobial properties [1]. The diary intake of EA with nutrients is irrelevant for therapeutic purposes and integrating it with functional foods could be a valid solution. Unfortunately EA poor water solubility [2, 3] and accordingly its low bioavailability don’t authorize its use as additive in food as well as its administration for clinical applications. On this background a research work has begun to improve its solubility, bioavailability, residence time and to maximize therapeutic activity. A first very satisfactory results, both in terms of improved solubility and of preserved antioxidant power, have been obtained by the realization of EA solid microdispersion in low methoxylated pectin as food compatible excipient and by applying spray drying technology. This innovative procedure, optimized by Design of Experiments (DoE), avoided the use of PEG, usually adopted as co-solvent to dissolve EA [2, 3, 4]. The obtained formulation was in the form of microsphere with a 22% Drug Loading and a 30 times improved water solubility and it was suitable both to design suspensions for oral administration and to be proposed as nutraceutical for functional food preparations. Then a second successful strategy was developed and in this communication we report the amazing results achieved adopting the not PAMAM hydrophilic fourth generation (1) and amphiphilic third generation (2) synthetic dendrimer scaffolds (Fig. 2) previously synthetized by us [5,6]. The successful outcome of the EA encapsulation was assessed both qualitatively and quantitatively through FTIR and 1H NMR technique. The new dendrimer formulations of EA were endowed with very optimal Drug Loading (46-53%) and above expectations with very high solubility in life compatible solvents such as water (300-1000 times higher than free EA). NMR estimated MW, potentiometric titration curve, mean buffer capacity and HPPT essay results of the new EA DDSs obtained are also reported. References: 1. J.M. Landete. Food Res. Int. 44, 1150 (2011). 2. Bala, Bhardwaj, Hariharan, Kharade, et al., J. Drug Target. 14, 27 (2006). 3. I. Bala, V. Bhardwaj, S. Hariharan, M.N.V. Ravi Kumar, J. Pharm. Biomed. Anal. 23, 206 (2006). 4. Sonaje et al., Pharm Res. 24, 899(2007). 5. S. Alfei, S. Catena. Polym. Int. 2018, https://doi.org: 10.1002/pi.5680. 6. S. Alfei, S. Catena. Polym. Adv. Technol. 2018: https://doi.org/10.1002/pat.4396.

Amazing increase of Ellagic Acid solubility by its entrapping into not PAMAM-structured biocompatible dendrimer scaffolds

Silvana Alfei;Raffaella Boggia;Federica Turrini;Brunella Parodi;Paola Zunin;Silvia Catena
2018

Abstract

Ellagitannins (ETs) and Ellagic acid (EA) (Fig.1) are bioactive polyphenols naturally present in numerous berries and nuts (i.e. pomegranates, black raspberries, raspberries, strawberries, walnuts almonds) and are endowed with antioxidant, anticancer, anti-inflammatory, antimicrobial properties [1]. The diary intake of EA with nutrients is irrelevant for therapeutic purposes and integrating it with functional foods could be a valid solution. Unfortunately EA poor water solubility [2, 3] and accordingly its low bioavailability don’t authorize its use as additive in food as well as its administration for clinical applications. On this background a research work has begun to improve its solubility, bioavailability, residence time and to maximize therapeutic activity. A first very satisfactory results, both in terms of improved solubility and of preserved antioxidant power, have been obtained by the realization of EA solid microdispersion in low methoxylated pectin as food compatible excipient and by applying spray drying technology. This innovative procedure, optimized by Design of Experiments (DoE), avoided the use of PEG, usually adopted as co-solvent to dissolve EA [2, 3, 4]. The obtained formulation was in the form of microsphere with a 22% Drug Loading and a 30 times improved water solubility and it was suitable both to design suspensions for oral administration and to be proposed as nutraceutical for functional food preparations. Then a second successful strategy was developed and in this communication we report the amazing results achieved adopting the not PAMAM hydrophilic fourth generation (1) and amphiphilic third generation (2) synthetic dendrimer scaffolds (Fig. 2) previously synthetized by us [5,6]. The successful outcome of the EA encapsulation was assessed both qualitatively and quantitatively through FTIR and 1H NMR technique. The new dendrimer formulations of EA were endowed with very optimal Drug Loading (46-53%) and above expectations with very high solubility in life compatible solvents such as water (300-1000 times higher than free EA). NMR estimated MW, potentiometric titration curve, mean buffer capacity and HPPT essay results of the new EA DDSs obtained are also reported. References: 1. J.M. Landete. Food Res. Int. 44, 1150 (2011). 2. Bala, Bhardwaj, Hariharan, Kharade, et al., J. Drug Target. 14, 27 (2006). 3. I. Bala, V. Bhardwaj, S. Hariharan, M.N.V. Ravi Kumar, J. Pharm. Biomed. Anal. 23, 206 (2006). 4. Sonaje et al., Pharm Res. 24, 899(2007). 5. S. Alfei, S. Catena. Polym. Int. 2018, https://doi.org: 10.1002/pi.5680. 6. S. Alfei, S. Catena. Polym. Adv. Technol. 2018: https://doi.org/10.1002/pat.4396.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/927587
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