Alginate-based complex fibers with the Janus morphology for controlled release of co-delivered drugs

Abstract

Hydrogels are soft materials consisting of a three-dimensional network of polymer chains. Over the years, hydrogels with different compositions have been developed as drug carriers for diverse biomedical applications, ranging from cancer therapy and wound care to the treatment of neurodegenerative and inflammatory diseases. Most of these carriers, however, are designed only to deliver single agents. Carriers based on hydrogels for co-delivery of multiple agents, with the release rate of each of the co-delivered agents tunable, are lacking. This study reports a one-pot method of fabricating alginate-based complex fibers with the Janus morphology, with carboxymethyl cellulose sodium functioning as a polymeric modifier of the properties of each of the fiber compartments. By using malachite green and minocycline hydrochloride as model drugs, the generated fibers demonstrate the capacity of enabling the release profile of each of the co-delivered drugs to be precisely controlled. Along with their negligible toxicity and the retention of the activity of the loaded drugs, the complex fibers reported in this study warrant further development and optimization for applications that involve co-delivery of multiple agents.

Keywords: Co-delivery; Complex fiber; Controlled release; Janus morphology; Tunable release profiles.

Graphical abstract

Fig. 1

A schematic diagram showing the procedures for generating a complex fiber with the Janus morphology.

Fig. 2

(A) The viability of 3T3 mouse fibroblasts and HEK293 cells, as assessed by the MTS assay, after 5-h treatment with different concentrations of Na-Alg and CMC-Na, (a) without or (b) with the subsequent 24-h post-treatment incubation. Data are presented as the means ± SD of triplicate experiments. (B) The impact of 5-h treatment with different concentrations of Na-Alg and CMC-Na, (a) without or (b) with the subsequent 24-h post-treatment incubation, on the proliferation of 3T3 mouse fibroblasts and HEK293 cells as assessed by cell counting. Data are presented as the means ± SD of triplicate experiments. (C) Hemolytic rates of erythrocytes with increasing concentrations of different complex fibers. (D) TG curves of Na-Alg, CMC-Na, and the C-A1C3 fiber.

Fig. 3

(A) SEM micrographs of the cross-sections of complex fibers consisting of (a) C-A1C0, (b) C-A3C1, (c) C-A1C1, and (d) C-A1C3. Scale bar = 500 µm. (B) Tensile stress-strain curves of different complex fibers. (C) The viscosity of different Na-Alg/CMC-Na blends at shear rates from 0 to 1 s^-1. (D) The G’ values and (E) G’’ values of different complex fibers at angular frequencies from 0.1 to 100 rad/s.

Fig. 4

(A) The swelling behavior of different complex fibers in simulated body fluid. Data are presented as the means ± SD of triplicate experiments. (B) The water content of fibers consisting of (i) C-A1C0, (ii) C-A3C1, (iii) C-A1C1, and (iv) C-A1C3. Data are presented as the means ± SD of triplicate experiments (*P < 0.05).

Fig. 5

(A) UV/Vis spectra of MG and MH. (B) The EE of C-A1C1 fibers with different diameters. Data are presented as the means ± SD of triplicate experiments. (C) The profiles of release of (a) MG and (b) MH from C-A1C1 fibers with different diameters. Data are presented as the means ± SD of triplicate experiments.

Fig. 6

(A) The EE of fibers with different mass percentages of CMC-Na. Data are presented as the means ± SD of triplicate experiments. (B) The profiles of release of (a) MG and (b) MH from fibers with different mass percentages of CMC-Na. Data are presented as the means ± SD of triplicate experiments. (C) (a) An optical image of a complex fiber with the Janus morphology, as well as (b) a magnified view of the cross-sectional area of a segment of the fiber. To enhance easy recognition of the Janus morphology, one of the compartments is stained with Congo red. (D) The profiles of release of MG and MH from a complex fiber with the Janus morphology: (a) C-A1C0 compartment for MG and C-A1C3 compartment for MH, and (b) C-A1C3 compartment for MG and C-A1C0 compartment for MH. Data are presented as the means ± SD.

Fig. 7

(A) Images showing the zone of inhibition induced by (a, f) filter paper soaked with distilled water, (b, g) MH-loaded C-A1C0, (c, h) MH-loaded C-A3C1, (d, i) MH-loaded C-A1C1, and (e, j) MH-loaded C-A1C3 for (a–e) E. coli and (f–j) S. aureus. Scale bar = 2 cm. (B) Area percentages of the zone of inhibition induced by different MH-loaded gels for (a) E. coli and (b) S. aureus. Data are presented as the means ± SD of triplicate experiments.