Fabrication of Ropivacaine/Dexamethasone-Eluting Poly(D, L-lactide-co-glycolide) Microparticles via Electrospraying Technique for Postoperational Pain Control

Abstract

Microencapsulation plays an important role in biomedical technology owing to its particular and attractive characteristics. In this work, we developed ropivacaine and dexamethasone loaded poly(D, L-lactide-co-glycolide) (PLGA) microparticles via electrospraying technique and investigated the release behavior of electrosprayed microparticles. The particle morphology of sprayed particles was assessed using scanning electron microscopy (SEM). The in vitro drug release kinetics were evaluated employing an elution method, and the in vivo pharmaceutical release as well as its efficacy on pain relief were tested using an animal activity model. The microscopic observation suggested that sprayed microparticles exhibit a size distribution of 5-6 µm. Fourier-transform infrared spectrometry and differential scanning calorimetry demonstrated the successful incorporation of pharmaceuticals in the PLGA particulates. The drugs-loaded particles discharged sustainably high concentrations of ropivacaine and dexamethasone at the target region in vivo for over two weeks, and the drug levels in the blood remained low. By adopting the electrospraying technique, we were able to prepare drug-embedded polymeric microparticles with effectiveness and with a sustainable capability for postoperative pain control.

Keywords: dexamethasone; electrospraying; microparticles; ropivacaine; sustained release.

Figure 1

The schematic of the electrospraying setup.

Figure 2

(A) A 5 cm-long skin incision wound was made at the middle of the abdominal wall. (B) The abdominal muscles were dissected until the exposure of the intra-abdominal organs, such as the stomach, intestine, liver, etc. (C) Drugs-loaded microparticles were implanted at the muscles of the abdominal wall. (D) The muscle, fascia, and skin were sutured with 3–0 Vicryl sutures.

Figure 3

A schematic model of the cage used to evaluate the animal activity.

Figure 4

Scanning electron microscopy image and particle size distribution of electrosprayed microparticles with PLGA:drugs ratio of (A) 3:1 and (B) 4:1. Scale bar = 10 µm.

Figure 5

(A) Fourier transform infrared spectra. (B) Thermogram of pure PLGA and drug-loaded PLGA microparticles.

Figure 6

(A) Daily and (B) cumulative release curves of ropivacaine from the electrosprayed microparticles.

Figure 7

(A) Daily and (B) cumulative release curves of dexamethasone from the electrosprayed microparticles.

Figure 8

In vivo release curves of (A) ropivacaine and (B) dexamethasone.

Figure 9

Monitored rat activity in the cage. Group A (red columns) was the control untreated group. Group B (green columns) received operation without any medication. Group C (blue columns) received surgery followed by the administration of drugs-loaded microparticles to the wound site (** p < 0.01).