Green decoration of graphene oxide Nano sheets with gelatin and gum Arabic for targeted delivery of doxorubicin

Abstract

Tri-nanocomposite system of biocompatible polymers (gelatin/gum arabic) functionalized onto graphene-oxide nanosheets for controlling the release of an anticancer, doxorubicin (DOX), was fabricated via green-biosynthesis. Biocompatibility and nano-size stability of the tri-nanocomposite was characterized by SEM, TEM, FTIR, XRD, and zeta-potential. Loading-efficiency, release-behavior and cytotoxic-activity of DOX-loaded-composite in WI-38 normal-lung-fibroblast and A549 lung-carcinoma cells were investigated. High DOX-loading (at pH 9.5), with pH-sensitive release from loaded-composite was achieved, with 25% and 77% DOX released, at physiological pH 7.4 and cancerous pH 5.3, respectively. Stability of tri-nanocomposite system was confirmed over 3-months storage at accelerated conditions, as presented by FTIR, XRD, TEM, zeta-potential and in-vitro release assays. High proliferative inhibitory effect of DOX loaded-composite, on A549-cells, with minimal toxicity on WI-38-cells, with IC₅₀ values of 51.9 ± 0.46 and 185±1.08 µg/mL, against A549 and WI-38, respectively. Proposed tri-nanocomposite offers a novel combination of gelatin/gum arabic with graphene-oxide for targeted drug-delivery and efficient anti-cancer therapy.

Keywords: Doxorubicin; Gelatin/gum arabic/graphene oxide tri-nanocomposite.

Fig. 1

SEM images and EDX charts of unloaded and DOX loaded tri-nanocomposite.

Fig. 2

TEM images of unloaded (A, B) and DOX loaded (C, D) tri-nanocomposite. SAED pattern of unloaded (E) and DOX loaded composite (F).; Particle size distribution analysed by TEM ImageJ processing software (G).

Fig. 3

FTIR (A, B); XRD patterns (C, D); and UV Spectra (E) of the prepared unloaded and DOX loaded tri-nanocomposite with their respective plain components. photographs confirming color change of the unloaded tri-nanocomposite from dark brown to red as a result of drug loading (F).

Fig. 4

stability of synthesized GL-GA-GO tri-nanocomposite against GO in different media.

Fig. 5

Calibration curve of plain DOX at 480 nm (A); with images showing effect of pH on DOX loading from the composites (B); actual loading and loading efficiency percentages of DOX onto GL/GA/GO tri-nanocomposite at: different pHs (C); different DOX concentrations (D) (mean± SD, n = 3).

Fig. 6

Release pattern (A) and corresponding release kinetics (B) of DOX loaded GL/GA/GO tri-nanocomposite in different pHs. Plain DOX was presented for comparison (mean± SD, n = 3).

Fig. 7

Cytotoxic activity of un loaded GL-GA-GO composite and DOX loaded composite against plain DOX, in both normal WI-38 lung fibroblast and A549 lung carcinoma cell lines at different concentrations (mean± SD, n = 3).

Fig. 8

Inverted microscope images of human lung normal (WI-38) cells treated with plain DOX, unloaded and DOX loaded composite at different concentrations. Magnification: × 40.

Fig. 9

Inverted microscope images of human lung cancer (A549) cells treated with plain DOX, unloaded and DOX loaded composite at different concentrations. Magnification: × 40.