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Original Research

Construction of catechol-grafted chitosan alginate/barium sulfate microcapsules for computed tomography real-time imaging and gastroretentive drug delivery

, , , , , , , , , , , & show all
Pages 6001-6018 | Published online: 31 Jul 2019

Figures & data

Figure 1 Characterization of Cat-CA/BS MCs. (A) UV-Vis spectra of CS, Cat6-CS, Cat13-CS, Cat27-CS. (B) FTIR spectra of CS, Cat6-CS, Cat13-CS, Cat27-CS. (C) 1H-NMR spectra of Cat6-CS, Cat13-CS, Cat27-CS, catechol.

Abbreviations: Cat-CA/BS MCs, catechol–chitosan/barium sulfate microcapsules; UV-Vis, ultraviolet–visible; CS, chitosan; Cat-CS, catechol–chitosan; FT-IR, Fourier transform–infrared; NMR, nuclear magnetic resonance.

Figure 1 Characterization of Cat-CA/BS MCs. (A) UV-Vis spectra of CS, Cat6-CS, Cat13-CS, Cat27-CS. (B) FTIR spectra of CS, Cat6-CS, Cat13-CS, Cat27-CS. (C) 1H-NMR spectra of Cat6-CS, Cat13-CS, Cat27-CS, catechol.Abbreviations: Cat-CA/BS MCs, catechol–chitosan/barium sulfate microcapsules; UV-Vis, ultraviolet–visible; CS, chitosan; Cat-CS, catechol–chitosan; FT-IR, Fourier transform–infrared; NMR, nuclear magnetic resonance.

Figure 2 Morphological characterization of microcapsules. Optical images of (A) A/BS MSs, (B) CA/BS MCs, and (C) Cat27-CA/BS MCs in water, and their corresponding size distributions.

Abbreviations: A/BS MSs, alginate/barium sulfate microspheres; CA/BS MCs, chitosan alginate/barium sulfate microcapsules; Cat27-CA/BS MCs, catechol-27–chitosan alginate/barium sulfate microcapsules.

Figure 2 Morphological characterization of microcapsules. Optical images of (A) A/BS MSs, (B) CA/BS MCs, and (C) Cat27-CA/BS MCs in water, and their corresponding size distributions.Abbreviations: A/BS MSs, alginate/barium sulfate microspheres; CA/BS MCs, chitosan alginate/barium sulfate microcapsules; Cat27-CA/BS MCs, catechol-27–chitosan alginate/barium sulfate microcapsules.

Scheme 1 Schematic illustration of the preparation process of Cat-CA/BS MCs and their applications in gastroretentive drug delivery and CT imaging. (A) Preparation of catecholylated chitosan; (B) preparation of Cat-CA/BS MCs; (C) Cat-CA/BS MCs for CT real-time imaging and mucosal adhesion-mediated gastric drug delivery. Abbreviations: Cat-CA/BS MCs, catechol-grafted chitosan alginate/barium sulfate microcapsules; CT, computed tomography; EDC, ethylcarbodiimide hydrochloride; NHS, N-hydroxysuccinimide; RH, ranitidine hydrochloride.

Scheme 1 Schematic illustration of the preparation process of Cat-CA/BS MCs and their applications in gastroretentive drug delivery and CT imaging. (A) Preparation of catecholylated chitosan; (B) preparation of Cat-CA/BS MCs; (C) Cat-CA/BS MCs for CT real-time imaging and mucosal adhesion-mediated gastric drug delivery. Abbreviations: Cat-CA/BS MCs, catechol-grafted chitosan alginate/barium sulfate microcapsules; CT, computed tomography; EDC, ethylcarbodiimide hydrochloride; NHS, N-hydroxysuccinimide; RH, ranitidine hydrochloride.

Figure 3 Scanning electron microscopy images of gradient barium sulfate nanocrystals on the wall of the Cat27-CA/BS MCs using a series of concentrations of sodium sulfate as the injection solution.

Abbreviation: Cat27-CA/BS MCs, catechol-27–chitosan alginate/barium sulfate microcapsules.

Figure 3 Scanning electron microscopy images of gradient barium sulfate nanocrystals on the wall of the Cat27-CA/BS MCs using a series of concentrations of sodium sulfate as the injection solution.Abbreviation: Cat27-CA/BS MCs, catechol-27–chitosan alginate/barium sulfate microcapsules.

Figure 4 Morphological characterization of Cat27-CA/BS MCs. (A and B) SEM images of outside surface of MCs. (C) SEM image of wall structure of MCs. (D) SEM image of barium sulfate crystal nanoclusters on the inside surface of Cat27-CA/BS MCs (pseudo-color). (E) X-ray diffraction pattern of Cat27-CA/BS MCs. (F) In vitro CT imaging of Cat27-CA/BS MCs with varying content.

Abbreviations: Cat27-CA/BS MCs, catechol-27–chitosan alginate/barium sulfate microcapsules; SEM, scanning electron microscopy; CT, computed tomography.

Figure 4 Morphological characterization of Cat27-CA/BS MCs. (A and B) SEM images of outside surface of MCs. (C) SEM image of wall structure of MCs. (D) SEM image of barium sulfate crystal nanoclusters on the inside surface of Cat27-CA/BS MCs (pseudo-color). (E) X-ray diffraction pattern of Cat27-CA/BS MCs. (F) In vitro CT imaging of Cat27-CA/BS MCs with varying content.Abbreviations: Cat27-CA/BS MCs, catechol-27–chitosan alginate/barium sulfate microcapsules; SEM, scanning electron microscopy; CT, computed tomography.

Figure 5 Evaluation of CS and Cate27-CS adhesive capacity on the mucin surface using SPR spectrum. The mucin solution was injected at the first arrow followed by a PBS wash and then CS (green solid line) and Cate27-CS solution (red solid line) were injected.

Abbreviations: CS, chitosan; Cat27, catechol-27.

Figure 5 Evaluation of CS and Cate27-CS adhesive capacity on the mucin surface using SPR spectrum. The mucin solution was injected at the first arrow followed by a PBS wash and then CS (green solid line) and Cate27-CS solution (red solid line) were injected.Abbreviations: CS, chitosan; Cat27, catechol-27.

Figure 6 In vivo CT scanning images of mice at different times after oral administration of CA/BS MCs, Cat6-CA/BS MCs, Cat13-CA/BS MCs, Cat27-CA/BS MCs.

Abbreviations: CA/BS MCs, chitosan alginate/barium sulfate microcapsules; Cat-CA/BS MCs, catechol–chitosan alginate/barium sulfate microcapsules.

Figure 6 In vivo CT scanning images of mice at different times after oral administration of CA/BS MCs, Cat6-CA/BS MCs, Cat13-CA/BS MCs, Cat27-CA/BS MCs.Abbreviations: CA/BS MCs, chitosan alginate/barium sulfate microcapsules; Cat-CA/BS MCs, catechol–chitosan alginate/barium sulfate microcapsules.

Figure 7 Near-infrared images of CA/BS MCs and Cat27-CA/BS MCs in real-time imaging tracer in vivo.

Abbreviations: CA/BS MCs, chitosan alginate/barium sulfate microcapsules; Cat27-CA/BS MCs, catechol-27–chitosan alginate/barium sulfate microcapsules.

Figure 7 Near-infrared images of CA/BS MCs and Cat27-CA/BS MCs in real-time imaging tracer in vivo.Abbreviations: CA/BS MCs, chitosan alginate/barium sulfate microcapsules; Cat27-CA/BS MCs, catechol-27–chitosan alginate/barium sulfate microcapsules.

Figure 8 Catechol-functionalized alginate/barium sulfate multifunctional microcapsules mediated RH delivery for acetic acid-induced mouse gastric ulcer treatment. (A) Release curve of RH-Cat27-CA/BS MSs/MCs in simulated gastric fluid. (B) Loss of basal body weight of mice under different treatments during gastric ulcer disease. (C) Gastric weight from each group of mice under different treatments (n=6 per group). (D) UI for each group of mice under different treatments (n=6 per group). Data are presented as mean ± standard error of the mean. *P<0.05, **P<0.01 vs acetic acid-alone-treated group on the same day.

Abbreviations: RH, ranitidine hydrochloride; Cat27-CA/BS MSs/MCs, catechol-27–chitosan alginate/barium sulfate microspheres/microcapsules; A/BS MCs, alginate/barium sulfate microcapsules; UI, ulcer index.

Figure 8 Catechol-functionalized alginate/barium sulfate multifunctional microcapsules mediated RH delivery for acetic acid-induced mouse gastric ulcer treatment. (A) Release curve of RH-Cat27-CA/BS MSs/MCs in simulated gastric fluid. (B) Loss of basal body weight of mice under different treatments during gastric ulcer disease. (C) Gastric weight from each group of mice under different treatments (n=6 per group). (D) UI for each group of mice under different treatments (n=6 per group). Data are presented as mean ± standard error of the mean. *P<0.05, **P<0.01 vs acetic acid-alone-treated group on the same day.Abbreviations: RH, ranitidine hydrochloride; Cat27-CA/BS MSs/MCs, catechol-27–chitosan alginate/barium sulfate microspheres/microcapsules; A/BS MCs, alginate/barium sulfate microcapsules; UI, ulcer index.

Figure 9 Pathological analysis of gastric tissues after distinct treatments using H&E staining assay after acetic acid induction. Magnification 100×. (A) Normal control. (B) Acetic acid induction. (C) A/BS MCs treatment. (D) RH treatment. (E) CA/BS MCs loading RH treatment. (F) Cat27-CA/BS MCs loading RH treatment.

Abbreviations: A/BS MCs, alginate/barium sulfate microcapsules; RH, ranitidine hydrochloride; CA/BS MCs, chitosan alginate/barium sulfate microcapsules.

Figure 9 Pathological analysis of gastric tissues after distinct treatments using H&E staining assay after acetic acid induction. Magnification 100×. (A) Normal control. (B) Acetic acid induction. (C) A/BS MCs treatment. (D) RH treatment. (E) CA/BS MCs loading RH treatment. (F) Cat27-CA/BS MCs loading RH treatment.Abbreviations: A/BS MCs, alginate/barium sulfate microcapsules; RH, ranitidine hydrochloride; CA/BS MCs, chitosan alginate/barium sulfate microcapsules.

Figure S1 Effect of sodium sulfate at different concentrations from 0.1% to 1.0% on the morphology of catechol 27–chitosan alginate/barium sulfate microcapsules.

Figure S1 Effect of sodium sulfate at different concentrations from 0.1% to 1.0% on the morphology of catechol 27–chitosan alginate/barium sulfate microcapsules.

Figure S2 Laser scanning confocal microscopy images of a wall section of catechol-27–chitosan/barium sulfate microcapsules under different excitation wavelengths. Abbreviation: FITC, fluorescein isothiocyanate.

Figure S2 Laser scanning confocal microscopy images of a wall section of catechol-27–chitosan/barium sulfate microcapsules under different excitation wavelengths. Abbreviation: FITC, fluorescein isothiocyanate.

Figure S3 Relative retention rates of A/BS MCs, CA/BS MCs, and Cat27-CA/BS MCs (n=5 per group) on the mucin-coated surface after PBS washing.Note: *Significant differences.

Abbreviations: A/BS MCs, alginate/barium sulfate microcapsules; CA/BS MCs, chitosan alginate/barium sulfate microcapsules; Cat27-CA/BS MCs, catechol-27–chitosan alginate/barium sulfate microcapsules.

Figure S3 Relative retention rates of A/BS MCs, CA/BS MCs, and Cat27-CA/BS MCs (n=5 per group) on the mucin-coated surface after PBS washing.Note: *Significant differences.Abbreviations: A/BS MCs, alginate/barium sulfate microcapsules; CA/BS MCs, chitosan alginate/barium sulfate microcapsules; Cat27-CA/BS MCs, catechol-27–chitosan alginate/barium sulfate microcapsules.

Figure S4 Macroscopic appearance and area of acetic acid-induced gastric ulcer after different treatments: normal; acetic acid; alginate/barium sulfate microcapsules (A/BS MCs); ranitidine hydrochloride (RH); ranitidine hydrochloride–chitosan alginate/barium sulfate microcapsules (RH-CA/BS MCs); and ranitidine hydrochloride–catechol-27–chitosan alginate/barium sulfate microcapsules (RH-Cat27-CA/BS MCs).

Figure S4 Macroscopic appearance and area of acetic acid-induced gastric ulcer after different treatments: normal; acetic acid; alginate/barium sulfate microcapsules (A/BS MCs); ranitidine hydrochloride (RH); ranitidine hydrochloride–chitosan alginate/barium sulfate microcapsules (RH-CA/BS MCs); and ranitidine hydrochloride–catechol-27–chitosan alginate/barium sulfate microcapsules (RH-Cat27-CA/BS MCs).