Data di Pubblicazione:
2013
Citazione:
Resveratrol-loaded nanocarrier for inner ear delivery / U.M. Musazzi, I. Youm, B.B.C. Youan - In: New frontiers in living cell encapsulation : 7. AItUN annual meeting : March 8-9, 2013, Perugia, Italy : abstract bookPerugia : Università degli studi di Perugia, 2013 Mar 09. - ISBN 9788890854408. - pp. 27-28 (( Intervento presentato al 7. convegno AItUN annual meeting : new frontiers in living cell encapsulation tenutosi a Perugia nel 2013.
Abstract:
Purpose: The aim of the work is to develop resveratrol-loaded nanocarriers (RES-NCs) for inner ear delivery and to evaluate in vitro toxicity on cochlear cell lines.
Materials and methods: RES-NCs are prepared by solvent-diffusion technique without surfactant. Resveratrol (RES), poly(D,L-lactide-co-glycolide) (PLGA) and poly(ε-caprolactone)–poly(ethylene glycol) diblock (PCL-PEG) are mixed in different ratios, dissolved in acetone and added dropwise to aqueous phase under constant stirring (acetone/water ratio 1/10). RES-NCs are washed and freeze-dried. Box-Behnken design (BBD) is used to study influence of RES-NCs composition on Z-size, PDI, Zeta-potential, drug encapsulation efficiency (EE%) and ratio between RES-NCs Z-size before and after freeze-drying (Sf/Si). In order to increase RES-NC stability during freeze-drying, lactose, mannitol, sucrose and trehalose are tested at different concentrations (1%, 5%, 10%, 15%, 20%w/v). Finally, MTS and LDH assays are carried out to check RES and Blank NCs toxicity after 24h incubation on two different cell lines: an organ of Corti model (HEI-OC1) and a stria vascularis one (SVK-1).
Results: BBD model is validated since all experimental responses fit with predicted values. Checkpoint analyses (bias NMT 10%) and Montecarlo simulation (response defect values NMT 10%) show good robustness in model capability to predict RES-NCs properties. The optimal formulation (desirability: 0.86), made of 7.4mg of RES, 3mg of PLGA and 5.3mg of PCL-PEG, correspond to Z-size of 136.2nm, PDI of 0.127, Z- potential of -26.80mV, EE% of 100.09% and Sf/Si of 3.30. All cryoprotectants increase RES-NCs stability during freeze-drying, disaccharides are more effective than mannitol. However, only trehalose in concentration higher than 15%w/v maintains Z-size and PDI in model space. In vitro toxicity studies show that RES can decrease cell viability only at concentration higher than 500μM, whereas blank NCs are toxic on HEI-OC1 in concentration more than 800μg/mL.
Conclusion: RES-NCs are successfully prepared by emulsion-diffusion technique and optimized by BBD. Moreover, threalose at 15%w/v guarantees RES-NCs stability during freeze-drying process.
Finally, in vitro studies show that RES and NCs are not toxic for cochlear cell lines in concentration lower than 500μg/mL and 800μg/mL respectively.
Tipologia IRIS:
03 - Contributo in volume
Elenco autori:
U.M. Musazzi, I. Youm, B.B.C. Youan
Link alla scheda completa:
Titolo del libro:
New frontiers in living cell encapsulation : 7. AItUN annual meeting : March 8-9, 2013, Perugia, Italy : abstract book