Sustainable release of LNT and calcium ion of CSL-gel
To assess the release property of loaded drugs in CSL-gel, we measured
the release rate of LNT at the corresponding time according to the
regression equation of LNT (y = 0.0028x + 0.0266, R2 =
0.9998, Figure S1 ). As shown in Figure 2a and2b , CSL-gel maintained a stable and cumulative release of LNT
from the first day to the 14 days after soaking. However, a substantial
amount of LNT was released from SL-gel on the first day and the LNT
release slightly increased with the extension of soaking time and
reached the maximum amount on the eighth day after soaking. At the ninth
day, a limited amount of LNT was released following the extension of the
soaking. Furthermore, we used Korsmeyer-Peppas and Higuchi models to
determine the release of LNT. Figure 2c showed that a clear
linear correlation (R2=0.989) between the cumulative
release rate and the logarithm of time from CSL-gel in the
Korsmeyer-Peppas model fitting curve was observed. Similarly, a high
linear correlation between the cumulative release rate and the square
root of time during the release of LNT from the CSL-gel
(R2=0.9823) was also observed in the Higuchi model
fitting curve (Figure 2d ). However, no linear correlation
between the cumulative release rate and the square root of time
(R2=0.8683) and between the cumulative release rate
and the logarithm of time (R2=0.933) of SL-gel was
observed. The corresponding dispersion coefficient (n) of SL-hydrogel
was 0.3089 (n < 0.43), indicating that the release of LNT from
SL-gel under these conditions followed Fickian diffusion (Table
3 ). In contrast, the dispersion coefficient (n) of CSL-gel was 0.6305
(0.43 < n < 0.85), which indicates the CSL-gel
followed non-Fick diffusion mechanism (Table 3 ). These findings
demonstrated that the chitosan shell controls the release of LNT from
the CSL-gel, resulting in the cumulative and sustainable release of LNT.
Soil is a complex system in which the properties, such as pH,
temperature, and ion concentration, are dynamic due to the impact of
external factors such as fertilization, irrigation, and rainfall[31]. The drug release from hydrogel will be
influenced by different soil environments. To assess the release rate of
LNT at different soil properties, we measured the release of LNT from
hydrogel at different pH, temperatures, and ion concentrations. As shown
in Figure 2e , the cumulative LNT release rate of CSL-gel highly
increased following the increased temperature, which is caused by the
high swelling of the hydrogel at a high temperature. Similarly, the
corresponding release rate of LNT from CSL-gel largely increased from
7.54% to 41.35% when the pH increased from 3 to 9 (Figure
2f ). This observation follows the fact that at low pH most of the
carboxyl groups on alginate are deionized and form strong hydrogen bonds
with hydroxyl groups, resulting in a tight shrinkage of the calcium
alginate pellet that prevents the LNT release from the CSL-gel.
Interestingly, we found that ion concentration present positively
regulated the release LNT from CSL-gel. As shown in Figure 2e ,
the cumulative release rate of LNT highly increased from 33.7% to
99.5% following the increased Na+ concentration from
0 to 0.8 M. The ion exchange between Na+ and
Ca2+ strengthens the electrostatic repulsion between
-COO-, which ultimately increases the swelling of the
hydrogel to stimulate the release of LNT [32].