Development of Functionalized Carbon Nano-Onions Reinforced Zein Protein Hydrogel Interfaces for Controlled Drug Release

Abstract

In the current study, poly 4-mercaptophenyl methacrylate-carbon nano-onions (PMPMA-CNOs = f-CNOs) reinforced natural protein (zein) composites (zein/f-CNOs) are fabricated using the acoustic cavitation technique. The influence of f-CNOs inclusion on the microstructural properties, morphology, mechanical, cytocompatibility, in-vitro degradation, and swelling behavior of the hydrogels are studied. The tensile results showed that zein/f-CNOs hydrogels fabricated by the acoustic cavitation system exhibited good tensile strength (90.18 MPa), compared with the hydrogels fabricated by the traditional method and only microwave radiation method. It reveals the magnitude of physisorption and degree of colloidal stability of f-CNOs within the zein matrix under acoustic cavitation conditions. The swelling behaviors of hydrogels were also tested and improved results were noticed. The cytotoxicity of hydrogels was tested with osteoblast cells. The results showed good cell viability and cell growth. To explore the efficacy of hydrogels as drug transporters, 5-fluorouracil (5-FU) release was measured under gastric and intestinal pH environment. The results showed pH-responsive sustained drug release over 15 days of study, and pH 7.4 showed a more rapid drug release than pH 2.0 and 4.5. Nonetheless, all the results suggest that zein/f-CNOs hydrogel could be a potential pH-responsive drug transporter for a colon-selective delivery system.

Keywords: acoustic cavitation method; cytocompatibility; pH-responsive drug release; zein/poly 4-mercaptophenyl methacrylate-carbon nano-onions hydrogels.

Figure 1

Synthetic illustration of (a) hydrogel preparation via acoustic cavitation, (b) cartoon diagram of hydrogel, (c) digital photograph of uniformly dispersed f-CNOs in DMEM after 1 year, and (d) digital photographs of fabricated UZCNOs hydrogel composite. f-CNOs indicates functionalized CNOs.

Figure 2

(a) Illustration of DLS particle size distribution, and (b) ξ-potential measurement of pristine CNOs and f-CNOs dispersions in DMEM.

Figure 3

SEM image of composite hydrogel after freeze-drying (a,d) CZCNOs, (b,e) MZCNOs, and (c,f) UZCNOs, respectively. (d–f) Indicates the high magnification SEM images of CZCNOs, MZCNOs, and UZCNOs hydrogels, respectively.

Figure 4

(a) FTIR spectra of (i) pure f-CNOs, (ii) pristine zein, and (iii) UZCNOs. (b) Tensile graph of (i) CZCNOs, (ii) MZCNOs, and (iii) UZCNOs hydrogels, respectively.

Figure 5

(a) Swelling ratio, (b) swelling rate, and (c) degradation curves of (i) CZCNO, MZCNOs, and UZCNOs hydrogels, respectively, in DMEM (pH 7.4) at room temperature.

Figure 6

The graph illustrating the cumulative release of 5-FU from CZCNOs, MZCNOs, and UZCNOs composite hydrogels in DMEM at (a) pH 2.0, (b) pH 4.5, (c) pH 7.4, and (d) pH 9.0 at 37 °C, respectively.

Figure 7

Cell viability of CZCNOs, MZCNOs, and UZCNOs composite hydrogels. Data represent mean ± SD (n = 3). Statistically significant difference (p < 0.05) was observed between the cell viability parameters of CZCNOs, MZCNOs, and UZCNOs samples.

Figure 8

Optical images of osteoblast cells on the surface of zein/f-CNOs composite hydrogels after 3 days of study: (a) The control (tissue culture plate), (b) CZCNOs, (c) MZCNOs, and (d) UZCNOs; green indicates LIVE cells, and red indicates DEAD, respectively. Scale bar = 100 μm.