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. 2021 Oct 15;13(20):3565.
doi: 10.3390/polym13203565.

Ionic and Enzymatic Multiple-Crosslinked Nanogels for Drug Delivery

Qian Tao  1 , Julong Zhong  1 , Rui Wang  1 , Yuzhu Huang  1
Affiliations

Ionic and Enzymatic Multiple-Crosslinked Nanogels for Drug Delivery

Qian Tao et al. Polymers (Basel). .

Abstract

Both ionic and enzymatic crosslink are efficient strategies for constructing network materials of high biocompatibility. Here chitosan was modified firstly and then crosslinked by these two methods for complementary advantages. The preparation methods and ionic crosslinkers can regulate the size and uniformity of the multiple-crosslinked nanogels. The multiple-crosslinked nanogels with the smallest size and the best uniformity was selected for the drug delivery. The drug-loading content and encapsulation efficiency were up to 35.01 and 66.82%, respectively. Their release behaviours are correlated with the pH value and the drug dosage. In general, the lower pH value and the lower drug dosage promoted the drug release. With the assistance of several kinetic models, it is found that drug diffusion plays a preponderant role in drug release, while polymer relaxation has a subtle effect. The multiple-crosslink resulting from ionic compounds and enzymes may provide a new perspective on developing novel biocompatible materials.

Keywords: drug delivery; enzymatic crosslink; ionic crosslink; multiple-crosslinked nanogel; natural polymeric materials.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The MC solution before (a) and after (b) HRP-catalysed crosslinking. The concentrations of MC, HRP, and H2O2 are 10 mg mL−1, 5 U mL−1, and 0.8 mM.
Figure 2
Figure 2
Hydrodynamic diameter distributions of multiple-crosslinked nanogels prepared with different methods. The concentrations of TPP (a) or Na2MoO4 (b) were 0.05 mg mL−1, respectively.
Figure 3
Figure 3
Hydrodynamic diameter distributions of multiple-crosslinked nanogels prepared with the method A and B. The concentrations of TPP or Na2MoO4 were 0.20 (a), 0.10 (b), 0.05 (c), 0.04 (d) mg mL−1, respectively.
Figure 4
Figure 4
(a) Scheme of 5-FU loading in multiple-crosslinked nanogel; (b) Hydrodynamic diameter distributions of MC/M/H-B4 nanogels with different 5-FU dosages.
Figure 5
Figure 5
Release profiles of MC/M/H-B4 nanogels (a–c) and the maximum cumulative 5-FU release from nanogels with different drug dosages at different pH values (d).
See this image and copyright information in PMC

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