A problem with solution: development of lipid-based colloidal nanocarriers for encapsulation of compounds with weak bioavailability

Abstract

Curcumin, the golden powder with weak bioavailability, also known for its anti-inflammatory and antioxidant properties, has been a target of great heed in various medical fields, namely in the treatment of neurodegenerative diseases [1]. In this particular field, multiple pharmacological targets, capable of promoting a decrease in peptidic aggregation [2], [3], oxidative stress [4] and neuroinflammation [5] have been identified. Considering that the level of biomedical activity is highly dependent on the proportion of curcuminoids, a prior study of the pharmaceutical profile of C.longa, the biggest source of curcuminoids, of C. aromatica, known for its medical relevance, and commercial curcumin, whose chemical constitution is known, was conducted [6]. This initial study was based in in vitro studies using a toolbox of biophysical techniques: derivative spectroscopy; quenching of intrinsic fluorescence of human serum albumin; dynamic and electrophoretic light scattering, differential scanning calorimetry and small and wide angle x-ray diffraction. The results obtained revealed that the studied bioactives possess low bioavailability, low solubility, fast breakdown, bioaccumulation, high affinity to HSA, membrane biophysical impairment and highlighted the need of encapsulating curcumin and extracts using nanocarriers. Following this rationale, and in order to optimize the use of such compounds in the treatment of neurodegenerative diseases, this research is focused on encapsulating curcumin and both the C. longa and C. aromatica extracts, in lipid-based colloidal nanosystems of dioctadecyldimethylammonium bromide (DODAB) and 1-oleoyl-rac-glycerol (MO) (1:2). The nanocarriers obtained by ethanolic injection of the bioactives in the nanosystems showed an encapsulation efficiency of approximately 100 %, being, thereby, highly efficient at encapsulating curcumin and extracts. Additionally, the same nanocarriers exhibited sizes inferior to 200 nm, high stability when stored up to 4 months and a positive superficial charge, which constitute attractive features for biomedical applications. A high affinity of curcumin and the studied extracts to the liposomes, as well as the ability to prevent interactions with plasma proteins, after successful pegylation, was also confirmed. As final remark, the formulations developed herein confirmed the antioxidant activity of the encapsulated natural compounds.