Preparation of novel ropivacaine hydrochloride-loaded PLGA microspheres based on post-loading mode and efficacy evaluation

Low encapsulation efficiency of the drug usually exist in hydrophilic drug which was embedded by hydrophobic materials directly in traditional method. In order to solve this problem, a novel preparation strategy which called "post-loading mode" was innovatively designed in this study: ropivacaine hydrochloride (ROP), a hydrophilic drug used in the field of anesthesia and analgesia, was encapsulated into the pre-prepared porous Poly (lactic-co-glycolic acid) (PLGA) microspheres; the porous PLGA microspheres (PLGA-Ms) with self-healing characteristic were used to obtain ROP-PLGA-Ms (with particle size around were 38 µm), in which drug loading (DL) was 8.72%. A rat sciatic nerve block model was established to evaluate the efficacy of ROP-PLGA-Ms. Exparel®, a bupivacaine liposome suspension approved by the FDA, was defined as reference agents in this study. The results showed that the injection of ROP, Exparel®, and ROP-PLGA-Ms were injected to the peripheral sciatic nerve could lead to motor dysfunction and sensory nerve block unanimously, and the onset time was less than 10 min for all cases. In addition, in comparison with ROP injection and Exparel®, the nerve block time of ROP-PLGA-Ms was significantly prolonged (P < 0.05). Effective analgesia duration of ROP-PLGA-Ms was about 5 h, 2.5 and 1.7 folds longer than that of ROP injection and Exparel®, respectively. The rats in each group could recover eventually within 8 h after administration. H&E showed that no inflammatory reaction was observed at the injection location. Analysis of blood biochemistry showed an insignificant difference between the microsphere experimental group and the negative group, which further indicated the safety of microsphere bioformulation.