Sustained release of levobupivacaine from temperature-sensitive injectable hydrogel for long-term local anesthesia in postoperative pain management.

Postoperative pain is a major concern for most of the surgical patients, and an inadequate postoperative pain control may cause a series of complications. With an effective pain control and lesser side effects, local anesthetics are preferred for use in postoperative pain management. However, the action duration of current local anesthetics is too short to meet the requirements of postoperative analgesia. In this study, an injectable levobupivacaine (LB)-loaded thermo-sensitive hydrogel system based on biodegradable poly(D,L-lactide)-poly(ethylene glycol)-poly(D,L-lactide) (PLEL) was developed for long-acting local anesthetic, in which the soluble charged cation form of LB (LB HCl) was partly alkalified to the poorly soluble base form (LB base). This hybrid LB loaded PLEL system (hLB/PLEL) is a free flowable liquid at room temperature and changes into a semi-solid hydrogel once injection in response to the physiological temperature. Then, the dissolved LB HCl could release firstly from the hydrogel contributing to a quick work, and the insoluble LB base dissolved and released gradually as the decrease of the pH during the biodegradation of PLEL hydrogel, resulting in a long-term LB release in local. The drug release behavior, pharmacokinetic, and biocompatibility of the thermo-sensitive hLB/PLEL were studied in vitro and in vivo. The anesthetic effects of hLB/PLEL system were evaluated in the rat models of sciatic nerve block, subcutaneous infiltration anesthesia and postoperative pain as well. This hLB/PLEL system generated a significantly prolonged analgesic effect in rat models, which produced approximately 7 times longer duration than 0.75% LB HCl and effectively relieved the spontaneous pain for 3 days. In general, the presented hLB/PLEL system can not only achieve a fast-acting but also sustainably release LB to block the nerve and significantly extend the effect of local analgesia, which means a promising candidate for long-acting postoperative pain management.

Comparison on anaerobic phosphorus release and recovery from waste activated sludge by different chemical pretreatment methods: Focus on struvite quality and benefit analysis.

Phosphorus recovery from waste activated sludge (WAS) is expected to alleviate the shortage of phosphate rock and reduce eutrophication. In this study, acid, alkali and sodium polyacrylate (PAAS) were compared to enhance phosphorus release and recovery from WAS. During anaerobic fermentation (AF) stage, the optimal pretreated conditions for ortho-phosphate release were the pH of 4 (AF 12 h), 13 (AF 12 h) and 22.4 g PAAS/L (AF 24 h) with the phosphorus release efficiencies of 40.9%, 62.6% and 31.7%, respectively. Acid, alkali and PAAS addition were beneficial for apatite phosphorus (AP), non-apatite inorganic phosphorus (NAIP) and organic phosphorus (OP) release from WAS, respectively. Strong acidic (pH = 4) and alkaline (pH = 12 and 13) conditions inhibited the release of soluble ammonia, while PAAS would not have a negative impact on the release of soluble ammonia. By means of precipitation crystallization, the ortho-phosphate could be almost recovered after acid/alkali pretreatment compared with PAAS (88.9%) at optimal Mg/P molar ratio of 1.5:1. The XRD, FT-IR and SEM-EDX analyses confirmed the main component in the product was struvite. The purity of the struvite in the product recovered from acid (named PreAC, 78.9%) and alkali (named PreAL, 89.6%) pretreated sludge were higher than that of the PAAS (named PrePA, 72.3%) by elemental analysis. The mercury and chromium content existed in PreAC were above the Control Standards of Pollutants in Sludge for Agricultural Use, whereas detected heavy metal elements level of the PreAL and PrePA were below the standard. By means of cost analysis, acid/alkali pretreatment could obtain economic benefits compared with PAAS. Thus, those discoveries would broaden the phosphorus recovery way to serve in practice.

CaCO3 supplementation alleviates the inhibition of formic acid on acetone/butanol/ethanol fermentation by Clostridium acetobutylicum.

OBJECTIVE: To investigate the inhibiting effect of formic acid on acetone/butanol/ethanol (ABE) fermentation and explain the mechanism of the alleviation in the inhibiting effect under CaCO3 supplementation condition. RESULTS: From the medium containing 50 g sugars l-1 and 0.5 g formic acid l-1, only 0.75 g ABE l-1 was produced when pH was adjusted by KOH and fermentation ended prematurely before the transformation from acidogenesis to solventogenesis. In contrast, 11.4 g ABE l-1 was produced when pH was adjusted by 4 g CaCO3 l-1. The beneficial effect can be ascribed to the buffering capacity of CaCO3. Comparative analysis results showed that the undissociated formic acid concentration and acid production coupled with ATP and NADH was affected by the pH buffering capacity of CaCO3. Four millimole undissociated formic acid was the threshold at which the transformation to solventogenesis occurred. CONCLUSION: The inhibiting effect of formic acid on ABE fermentation can be alleviated by CaCO3 supplementation due to its buffering capacity.