Hydrogen-bonded multilayer of pH-responsive polymeric micelles with tannic acid for surface drug delivery

Abstract

We report the design of a platform for the delivery of hydrophobic drugs conjugated to block copolymer micelles via pH-responsive linkage that are assembled within hydrogen-bonded polymer multilayer thin films.

Fig 1

Growth curve of (Dox-micelle/TA)_n multilayer prepared in phosphate buffer (10 mM, pH 7.4). Absorbance was measured at 280 nm and the film thickness was measured by surface profilometer (n = 5).

Fig 2

3D height-mode AFM images of (a) Dox-micelle (b) (Dox-micelle/ TA)₂₀ multilayer deposited on a silicon wafer. Scale of both images is 1 µm × 1 µm × 500 nm.

Fig 3

(a) Release profiles of (Dox-micelle/TA)₄₀ multilayer at various pH conditions. (b) In vitro cell assay against HeLa cells with different film compositions. The release profile was normalized to the value of release of Dox at the pH 4 condition after 48 h, after which does not exhibit any signal of Dox release.

Fig 4

(Left) Bright-field and (right) fluorescence images of in vitro cell assay against HeLa cells with (top) Dox releasing film and (bottom) control PBS. Cells were plated at equal confluence on day 0 (25K cells per well). Live cells are stained with calcein AM at day 4. All images are in 10× magnification.

Scheme 1

(a) Schematic representation of hydrogen-bonding LbL assembly of doxorubicin containing micelles with tannic acid. (b) Synthetic routes for PEO-b-PHEMA-Dox.