Injectable PLGA-Coated Ropivacaine Produces A Long-Lasting Analgesic Effect on Incisional Pain and Neuropathic Pain

Abstract

The management of persistent postsurgical pain and neuropathic pain remains a challenge in the clinic. Local anesthetics have been widely used as simple and effective treatment for these 2 disorders, but the duration of their analgesic effect is short. We here reported a new poly lactic-co-glycolic acid (PLGA)-coated ropivacaine that was continuously released in vitro for at least 6 days. Perisciatic nerve injection of the PLGA-coated ropivacaine attenuated paw incision-induced mechanical allodynia and heat hyperalgesia during the incisional pain period, and spared nerve injury-induced mechanical and cold allodynia for at least 7 days postinjection. This effect was dose-dependent. Perisciatic nerve injection of the PLGA-coated ropivacaine did not produce detectable inflammation, tissue irritation, or damage in the sciatic nerve and surrounding muscles at the injected site, dorsal root ganglion, spinal cord, or brain cortex, although the scores for grasping reflex were mildly and transiently reduced in the higher dosage-treated groups.Perspective: Given that PLGA is an FDA-approved medical material, and that ropivacaine is used currently in clinical practice, the injectable PLGA-coated ropivacaine represents a new and highly promising avenue in the management of postsurgical pain and neuropathic pain.

Enzyme-Catalyzed One-Step Synthesis of Ionizable Cationic Lipids for Lipid Nanoparticle-Based mRNA COVID-19 Vaccines

“…Tissue images indicated that there was no AA3-DLin LNP induced inflammation detected after comparison with PBS control groups (Figure S8 and S9). − …”

Lipid‐Polymer Hybrid “Particle‐in‐Particle” Nanostructure Gene Delivery Platform Explored for Lyophilizable DNA and mRNA COVID‐19 Vaccines

“…One of the main advantages of the PLGA NP delivery vector is the sustained release of encapsulated payload, which is usually governed by diffusion and degradation processes. [ 17 , 24 , 29 , 30 ] The cumulative release profiles of both plasmid and mRNA using PNP/C12‐PBAE NPs indeed showed sustained release behavior compared and reached a peak of up to 96% gene released over 8 days after a quick release within the first 24 h (Figure 3G,H ). These results clearly indicate that the PNP/C12‐PBAE NP displays a prolonged gene release behavior for both plasmid DNA and mRNA compared with C12‐PBAE formulations which have no PLGA‐PEG polymeric vector.…”

“…Furthermore, the histopathology and immunofluorescence assays of the proinflammatory biomarker IL‐6 in muscle tissues surrounding the PNP injection site were evaluated after 5 days post‐injection and the results showed no observable PNP nanoparticle‐mediated inflammation when compared with the control PBS injected group (Figures S6 and S7 , Supporting Information). [ 29 , 33 ]…”

Synthesis of nanocapsules blended polymeric hydrogel loaded with bupivacaine drug delivery system for local anesthetics and pain management

“…It is well documented that CS-GP hydrogel and CS-GP/PC polymeric hydrogel have excellent encapsulation efficiencies (EE) and drug loading (DL) mainly due to their porous structures and numerous functional groups (Tian et al., 2021 ). The EE and DL values of the fabricated CS-GP hydrogel and CS-GP/PC polymeric hydrogel were calculated, and the results obtained were summarized in Table 1 .…”