Bile acid-based drug delivery systems for enhanced doxorubicin encapsulation: Comparing hydrophobic and ionic interactions in drug loading and release

Abstract

Doxorubicin (Dox) is a drug of choice in the design of drug delivery systems directed towards breast cancers, but is often limited by loading and control over its release from polymer micelles. Bile acid-based block copolymers present certain advantages over traditional polymer-based systems for drug delivery purposes, since they can enable a higher drug loading via the formation of a reservoir through their aggregation process. In this study, hydrophobic and electrostatic interactions are compared for their influence on Dox loading inside cholic acid-based block copolymers. Poly(allyl glycidyl ether) (PAGE) and poly(ethylene glycol) (PEG) were grafted from the cholic acid (CA) core yielding a star-shaped block copolymer with 4 arms (CA-(PAGE-b-PEG)4) and then loaded with Dox via a nanoprecipitation technique. A high Dox loading of 14 wt% was achieved via electrostatic as opposed to hydrophobic interactions with or without oleic acid as a cosurfactant. The electrostatic interactions confer a pH responsiveness to the system. 50% of the loaded Dox was released at pH 5 in comparison to 12% at pH 7.4. The nanoparticles with Dox loaded via hydrophobic interactions, did not show such a pH responsiveness. The systems with Dox loaded via electrostatic interactions showed the lowest IC50 and highest cellular internalization indicating the pre-eminence of this interaction in Dox loading. The blank formulations are biocompatible and did not show cytotoxicity up to 0.17 mg/mL. The new functionalized star block copolymers based on cholic acid show great potential as drug delivery carriers.