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 toward 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)) 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 IC 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.

Regulating Protein Corona Formation and Dynamic Protein Exchange by Controlling Nanoparticle Hydrophobicity

“…Foreign hydrophobic molecules or NPs are harmful to biological systems by disrupting cell membrane and protein folding. On the other hand, a certain degree of hydrophobicity was needed for drugs to cross cell membranes or biological barriers (Cunningham et al, 2018). Protein corona formation may change the hydrophobicity of NPs.…”

Steroid-Based Supramolecular Systems and their Biomedical Applications: Biomolecular Recognition and Transportation

“…To improve the hydrophilic, long-retention/stealth effect, and biocompatibility, polyethylene glycol (PEG) was often introduced to steroid scaffolds [72]. In fact, PEGylated bile acids were synthesized to further prepare self-emulsifying drug delivery systems (SEDDSs), which could enhance the solubility and absorption of poor water-soluble antitumor agent (doxorubicin [73]) or antibiotics (itraconazole [74]), thus providing a significant enhancement of solubility and bioavailability of these small molecular drugs. The emulsions consisted of spherical micelles with a mean hydrodynamic diameter around 100-220 nm, with good biocompatibility (low cytotoxic and hemolytic effect).…”

pH-Responsive Micelles Assembled by Three-Armed Degradable Block Copolymers with a Cholic Acid Core for Drug Controlled-Release

“…Zhu and co-workers reported the synthesis of series polymers based on CA, and using them in drug delivery systems. Research indicated that the micelles formed from cholic acid-based star polymers had a lower density than linear polymers with a similar structure, forming an internal reservoir that can accommodate a larger amount of hydrophobic therapeutic drug, showing their advantages in terms of biocompatibility and drug loading [31,32,33,34,35]. The drug loading and encapsulation efficiency of these nanoparticles reached up to 35 wt % and higher than 89%, respectively, improving bioavailability and pharmacokinetics of the drug.…”