Micelle controlled release of 5-fluorouracil: Follow the guideline for good polymer–drug compatibility

• Flory–Huggins interaction parameter was used to reckon the drug–polymer affinity.
• With CAB groups pending on PCL, copolymer showed enhanced 5-FU-polymer affinity.
• mPEG-b-PCL copolymer with CAB groups pending (100% substitution) was synthesized.
• A 5-FU micelle carrier superior to micelle prepared by mPEG-b-PCL was developed.
• Tailored pendant groups on PCL lead to optimal drug loading and release behavior.

Flory–Huggins interaction parameter (χpd) was introduced to qualitatively evaluate the drug–polymer compatibility between hydrophilic 5-fluorouracil (5-FU) and hydrophobic core block, which was formed by poly[γ-(carbamic acid benzyl ester)-ɛ-caprolactone] (PCABCL) and poly(ɛ-caprolactone) (PCL). The calculation results indicated that PCABCL had better affinity with 5-FU than PCL. Thus, a series of diblock polymers monomethoxy poly(ethylene glycol)-b-poly[γ-(carbamic acid benzyl ester)-ɛ-caprolactone] (mPEG45-b-PCABCLn) was synthesized, followed by the preparation of 5-FU loaded micelles. The introduction of γ-(carbamic acid benzyl ester) (CAB) group significantly decreased the crystallinity of copolymers and increased the hydrophilicity of the micellar core, leading to an improved drug loading content. These micelles had high stability and spherical morphology. The release behavior could be turned by the length of core-forming block. Moreover, micelles prepared by mPEG45-b-PCABCL19 displayed the highest 5-FU loading content and the most controlled release behavior. These blank micelles showed very low toxicity against HCT116 cancer cells. Meanwhile 5-FU loaded micelles exhibited a concentration dependent increase in HCT116 cell death by inducing cell apoptosis in vitro. These results indicated that these micelles have great potential in cancer therapy.

Non-covalent bonding, such as hydrogen bonding interaction, polarity attraction, π–π interaction, etc., is widely existed between carriers and drugs. The presence of these forces is a vigorous supplement to hydrophobic interaction, which has great influence on drug loading and release behavior.Figure optionsDownload as PowerPoint slide