Exploitation of amaranth oil fractions enriched in squalene for dual delivery of hydrophilic and lipophilic actives

Abstract The study describes an ideal approach to increase the co-encapsulation of two water and lipid-soluble drugs in the same delivery system. The main purpose is represented by the exploitation of oil fractions isolated from amaranth seeds for the development of squalene-based nanocarriers able for a dual release of one antitumor drug, pemetrexed and one bio-flavonoid, hesperidin. The co-encapsulated nanocarriers presented unique nanoassembly morphology and showed excellent stability against aggregation. A delimited repartition of both actives, mainly in oily nanoconfinements of lipid nanocariers has been indicated by scanning calorimetry. The entrapment efficiency study revealed a great encapsulation effect with values reaching 94% for hesperidin and 89% for pemetrexed . These values are associated with a high ability of squalene-nanocarriers to capture free radicals. The greatest antioxidant activity was determined for nanocarriers that co-encapsulate 1.4% drugs, e.g. , 97.3 and 98.2%. In vitro co-release tests demonstrated that pemetrexed and hesperidin were gradually released despite of their different lipophilicity. The most concentrated squalene fraction assures a slower release of both actives. The cumulative results showed that the applied strategy is a promising approach to improve the performance of medical treatments used to prevent and treat diseases associated with tumor and oxidative stress.