Sustained-Release Esketamine Based Nanoparticle-Hydrogel Delivery System for Neuropathic Pain Management

Figures & data

Figure 1 Esketamine-encapsulated PLGA nanoparticles topical application diagram. Spinal nerve ligation in mice (A); ES NPs-HA: hydrogel-containing esketamine-encapsulated nanoparticles (B); Spinal nerve root administration (C).

Figure 2 The Characterization of ES NPs-HA. SEM images of the esketamine-encapsulated PLGA nanoparticles (A) Scale bar: 500 nm; Particle size distribution of esketamine-encapsulated PLGA nanoparticles (B); SEM images of hyaluronic acid hydrogel (C) Scale bar: 5 μm; SEM images of ES NPs-HA (D) Scale bar: 5 μm.

Figure 3 In vitro drug release characteristics of ES NPs-HA. Standard Esketamine release curve. (A) Daily release of ES NPs-HA. (B) Cumulative release of ES NPs-HA (C).

Figure 4 In vivo uptake of nanoparticles. Rhodamine-conjugated PLGA nanoparticles were detected on postoperative day 5 (A); Empty PLGA nanoparticles (B). Scale bar: 50 µm.

Figure 5 Effect of ES NPs-HA on neuropathic pain. Experimental timeline of this study (A) Mechanical pain threshold in mice after spinal nerve ligation (B) (n=6/group); Effect of a single treatment of esketamine on mechanical pain in SNL mice (C) (n=8/group); The effect of ES NPs-HA administration on mechanical pain in SNL mice (D) (n=8/group). Data are expressed as the mean ± SEM. *P <0.05; Two-way RM ANOVA followed by the Bonferroni test.

Figure 6 Effect of ES NPs-HA on the excitability of DRG neurons in SNL mice. The number of Aps in DRG neurons of mice receiving ES NPs-HA treatment was recorded, 5 days after SNL (A); The representative traces of action potentials in responding to 100, 200, and 300 pA ramp current stimulation (B–E). Sham (B); SNL (C); SNL+NC NPs-HA (D); SNL+ES NPs-HA (E). **P<0.01, ***P<0.001, vs SNL+NC Ps-HA; ^###P<0.001, vs Sham. Two-way RM ANOVA followed by the Bonferroni test. Sham: Sham surgery group; SNL: Spinal nerve ligation group; SNL+NC NPs-HA: Injection of hydrogel-containing 0.9% saline-encapsulated nanoparticles after SNL; SNL+ES NPs-HA: Injection of hydrogel-containing esketamine-encapsulated nanoparticles after SNL.

Figure 7 Effect of ES NPs-HA on spinal astrocytes in mice. On day 5 postoperative, L4 spinal sections were taken and incubated with anti-GFAP antibodies. Sham (A); SNL (B); SNL+ES NPs-HA (C). Scale bar: 100 µm.

Figure 8 Tissue reactions of ES NPs-HA. HE staining of nerves 14d after treatment with (A) Control: 0.9% NaCl, (B) ES: esketamine, or (C) ES NPs-HA: hydrogel-containing esketamine-encapsulated nanoparticles. Scale bar: 100 μm.