Formulation and optimization of bioinspired rosemary extract loaded PEGylated nanoliposomes for potential treatment of Alzheimer's disease using design of experiments

Abstract

Based on the latest scientific knowledge about the antioxidant stress being the main trigger factor for the development of Alzheimer's disease (AD) and the advantages of nanoliposomes (NLs) as drug carriers for targeted brain delivery, the aim of this study was design, development and optimization of rosemary extract (RE) loaded PEGylated NLs for potential AD treatment. Central composite design was applied in order to obtain the optimal formulations. NLs dispersions were prepared by modified dry lipid film hydration method and were investigated in terms of their physicochemical and biopharmaceutical properties. Optimized NLs samples were characterized with D50 around ~120 nm with narrow unimodal distribution, negative Zeta potential (-18.50 to -48.3 mV), followed by high drug encapsulation efficiency (~90%) and prolonged drug release during 24 h (24.83-48.39%). All optimal NLs samples showed statistically significant higher antioxidant capacity (>94.15%) compared to RE (90.04%). Highest amount of adsorbed plasma proteins, in plasma of healthy volunteers and AD patients, was obtained for the formulation with no PEG on its surface, while IR-ATR spectrophotometric analysis pointed out that the formulations with larger PEG content showed a stronger hydrogen bonding between PEG and BSA. The protein corona formation was also confirmed with in vitro stability studies.