Hydrophilic carriers for encapsulation of hydrophobic drug cannabidiol: Vaterite CaCO3 crystals and multilayer microgels made of sustainable polymers.

Vaterite is one of the polymorphs of CaCO3 that has been used as sustainable drug carrier because of tuned sizes, porosity, low production costs, non-toxic and biocompatible/degradable nature. It can also be used as a sacrificial template for hard templating of polymer-based structures such as multilayer microgels. Both vaterites and microgels are highly advantageous offering protection and regulation the release of the drugs, thereby enhancing drug bioavailability. However, loading of hydrophobic drugs in such carriers is still a challenge. In this study, a water-insoluble drug cannabidiol (CBD) was loaded into both vaterite crystals and microgels made of sustainable biopolymers. Surface-supported vaterite crystals were synthesized via direct mixing of CaCl2 and Na2CO3 in water-ethanol mixture (20-70% ethanol). Increase of ethanol content results in the formation of smaller crystals of needle- and cauliflower-like shapes. CBD was loaded into crystals either by co-synthesis or post-loading providing up to ca 4% w/w of CBD. Crystal sizes can easily be varied in the range of microns (here 3-13 μm) and beyond by tweaking the synthesis conditions (e.g. salt stirring time and speed). Microgels were formed by coating of vaterite crystals with five layers of oppositely charged biopolymers and showed excellent stability in ethanol-water mixture. Hydroxypropyl trimethyl ammonium chitosan chloride based microgels were loaded with ca 1% w/w of CBD via adsorption. Mechanism of CBD loading and factors affecting stability of microgels in ethanol-water solutions are discussed in view of dynamics of interpolymer interactions in multilayers. These findings highlight the potential of sustainable hard (vaterite CaCO3) and soft (polymer microgels) structures as a versatile platform for encapsulation of hydrophobic drugs like CBD, offering tuneable systems for drug delivery applications.