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. 2017 Aug 16;15(8):257.
doi: 10.3390/md15080257.

Synthesis and Evaluation of a Sodium Alginate-4-Aminosalicylic Acid Based Microporous Hydrogel for Potential Viscosupplementation for Joint Injuries and Arthritis-Induced Conditions

Dharmesh R Chejara  1 , Mostafa Mabrouk  2   3 , Pradeep Kumar  4 , Yahya E Choonara  5 , Pierre P D Kondiah  6 , Ravindra V Badhe  7 , Lisa C du Toit  8 , Divya Bijukumar  9 , Viness Pillay  10
Affiliations

Synthesis and Evaluation of a Sodium Alginate-4-Aminosalicylic Acid Based Microporous Hydrogel for Potential Viscosupplementation for Joint Injuries and Arthritis-Induced Conditions

Dharmesh R Chejara et al. Mar Drugs. .

Abstract

A microporous hydrogel was developed using sodium alginate (alg) and 4-aminosalicylic acid (4-ASA). The synthesized hydrogel was characterized using various analytical techniques such as Fourier transform infrared spectroscopy (FTIR), Carbon-13 nuclear magnetic resonance (13C-NMR), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). Additonal carboxyl and hydroxyl functional groups of 4-ASA provided significant lubrication and stress-triggered sol-gel transition to the conjugated hydrogel. In addition, cytotoxicity analysis was undertaken on the conjugated hydrogel using human dermal fibroblast-adult (HDFa) cells, displaying non-toxic characteristics. Drug release profiles displaying 49.6% in the first 8 h and 97.5% within 72 h, similar to the native polymer (42.8% in first 8 h and 90.1% within 72 h). Under applied external stimuli, the modified hydrogel displayed significant gelling properties and structure deformation/recovery behaviour, confirmed using rheological evaluation (viscosity and thixotropic area of 8095.3 mPas and 26.23%, respectively). The modified hydrogel, thus, offers great possibility for designing smart synovial fluids as a biomimetic aqueous lubricant for joint-related injuries and arthritis-induced conditions. In addtion, the combination of thixotropy, non-toxicity, and drug release capabilities enables potential viscosupplementation for clinical application.

Keywords: 4-aminosalicylic acid (4-ASA); arthritis; hydrogel; sodium alginate; viscosupplementation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
FTIR spectra of (a) Alg, (b) Alg-4-ASA (1:1), (c) 4-ASA; 13C-NMR spectra of (d) Alg, (e) 4-ASA, and (f) Alg-4-ASA (1:1).
Figure 2
Figure 2
(A) Powder X-ray diffraction study of (a) Alg, (b) 4-ASA and (c) Alg-4-ASA (1:1); and (B) DSC analysis of (a) Alg (b) Alg-4-ASA (1:1), and (c) 4-ASA.
Figure 3
Figure 3
Rheological studies of Alg-4-ASA conjugate gels: (a) shear viscosity, (b) hysteresis loop area experiment, (c) oscillation frequency sweep experiment, (d) time ramp sweep experiment, (e) temperature ramp sweep experiment, and (f) oscillatory stress sweeps studies of hydrogel against the control polymer (concentration of each sample was 3% (w/v), pH (5–6)). All rheological analyses were carried out at 37 °C.
Figure 3
Figure 3
Rheological studies of Alg-4-ASA conjugate gels: (a) shear viscosity, (b) hysteresis loop area experiment, (c) oscillation frequency sweep experiment, (d) time ramp sweep experiment, (e) temperature ramp sweep experiment, and (f) oscillatory stress sweeps studies of hydrogel against the control polymer (concentration of each sample was 3% (w/v), pH (5–6)). All rheological analyses were carried out at 37 °C.
Figure 4
Figure 4
Scanning electron micrographs of hydrogels: (a) Alg-4-ASA (1:0.5) and (b) Alg-4-ASA (1:1).
Figure 5
Figure 5
Cell viability of human dermal fibroblast-adult cells incubated with different concentrations of Alg-4-ASA (1:1) hydrogel.
Figure 6
Figure 6
The release profiles of aspirin loaded hydrogels within 72 h in PBS (pH = 7.4) at 37 °C.
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