Drugs with poor lipid and water solubility are some of the most challenging to formulate in nanocarriers, typically
resulting in low encapsulation efficiencies and uncontrolled release profiles. PEGylated nanocapsules (PEG-NC) are
known for their amenability to diverse modifications that allow the formation of domains with different physicochemical
properties, an interesting feature to address a drug encapsulation problem. We explored this problem by encapsulating in
PEG-NC the promising anticancer drug candidate F10320GD1, used herein as a model for compounds with such characteristics.
The nanocarriers were prepared from Miglyol®, lecithin and PEG-sterate through a solvent displacement technique.
The resulting system was a homogeneous suspension of particles with size around 200 nm. F10320GD1 encapsulation
was found to be very poor (<15%) if PEG-NC were prepared using water as continuous phase; but we were able to
improve this value to 85% by fixing the pH of the continuous phase to 9. Interestingly, this modification also improved
the controlled release properties and the chemical stability of the formulation during storage. These differences in pharmaceutical
properties together with physicochemical data suggest that the pH of the continuous phase used for PEG-NC
preparation can modify drug allocation, from the external shell towards the inner lipid core of the nanocapsules. Finally,
we tested the bioactivity of the drug-loaded PEG-NC in several tumor cell lines, and also in endothelial cells. The results
indicated that drug encapsulation led to an improvement on drug cytotoxicity in tumor cells, but not in non-tumor endothelial
cells. Altogether, the data confirms that PEG-NC show adequate delivery properties for F10320GD1, and underlines
its possible utility as an anticancer therapy.