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

doi:10.7503/cjcu20180408

Abstract

Abstract:

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 for CTX provided by film component CHI. CTX can be quickly released from the polymeric films because of the brea-kage 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 diffe-rential release of multiple therapeutic agents.

Key words: Layer-by-Layer(LbL) assembly, Polymeric complex, Polymeric film, Drug delivery, Differential release

CLC Number:

O631

TrendMD:

CHEN Dongdong, SONG Wenzhi, LI Hui, HE Dan, SUN Junqi, YIN Wanzhong. Layer-by-layer Assembled Polymeric Complexes Films for High Loading and Differential Release of Macromolecular and Small Molecular Drugs^†[J]. Chem. J. Chinese Universities, 2019, 40(3): 592.

Figures/Tables 7

Scheme 1 Schematic illustration of the formation of CHI-CSS polyelectrolyte complexes(Ⅰ), and the layer-by-layer assembly process for the fabrication of CHI-CSS/HA polymeric films(Ⅱ)

Fig.1 Hydrodynamic diameter distribution curve of the aqueous CHI-CSS complex dispersion at pH=6.0Inset is the photograph of the aqueous CHI-CSS complex dispersion.

Fig.2 Typical QCM frequency decreases for the alternate deposition of CHI-CSS complexes(■) and HA(●)(A), thickness of CHI-CSS/HA films as a function of the number of deposition cycles(B) and top view(C) and cross-sectional(D) SEM images of (CHI-CSS/HA)×13 films

Fig.3 Time-depended release profile of CTX(A) and CSS(B) from (CHI-CSS/HA)×13 films in PBS(0.01 mol/L) containing lysozyme(2 mg/mL) at pH=7.4 and 37 ℃

Fig.4 Inhibition of E. coli(A, C) and B. subtilis(B, D) growth by release of CTX from (CHI-CSS/HA)×13 films loaded with CTXAgar plates of E. coli.(A) and B. subtilis(B) treated with the control sample(bare silicon substrate) and (CHI-CSS/HA)×13 films with and without CTX. The growth curves of E. coli(C) and B. coli(D) incubated for 24 h with the control sample(bare silicon substrate) and (CHI-CSS/HA)×13 films with CTX.

Fig.5 Bioactivity of released CSS from (CHI-CSS/HA)×13 films on wound healing in vitroThe mouse fibroblast L929 cells with wound gap incubated for 48 h with growth medium containing released CSS(A), free CSS(B) and blank PBS(C). (D) Statistical analysis of wound healing for L929 cells incubated with blank PBS(negative control), free CSS(positive control) and released CSS.

Fig.6 SEM images of surgical sutures(A, C) and bandages(B, D) before(A, B) and after(C, D) depositing with (CHI-CSS/HA)×13 films

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