Layer-by-layer Assembled Polymeric Complexes Films for High Loading and Differential Release of Macromolecular and Small Molecular Drugs

The layer-by-Layer (LbL) assembled polymeric complexes films capable of differential release of macromolecular and small molecular drugs were fabricated by utilizing chitosan (CHI) hydrochloride-chondroitin sulfate sodium(CSS) complexes( denoted as CHI-CSS complexes) as building blocks and post-diffusion of ceftriaxone sodium (CTX). The CHI-CSS complexes were prepared by pre-assembled macromolecular drugs CSS with CHI , and then were LbL assembled with hyaluronic acid (HA) to produce CHI-CSS/HA polymeric films. The small molecular drugs CTX were loaded into the CHI-CSS/HA polymeric films through a postdiffusion process. The as-prepared CHI-CSS/HA polymeric films possess high loading capacity because of the high encapsulation amount of CSS in CHI-CSS complexes and plenty of electrostatic binding sites 14 CTX provided by film component CHI. CTX can be quickly released from the polymeric films because of the breakage of its electrostatic interaction with film component CHI. Meanwhile, the CSS can be released in sustained manner by enzymatic degradation of the films. The synergetic therapeutic effects can be achieved by fast release of antibiotic drug CTX to effectively eliminate bacteria and by sustained release of CSS to promote wound healing. The present work provides a facile way to fabricate polymeric films for high loading and differential release of multiple therapeutic agents.