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Besides peripheral nerve injury, the acute inflammation is one of the pathological features of tissues after surgery, which exacerbates the postoperative pain, especially in the first 48 h after the surgery. Multimodal analgesia (MMA), such as the combination of non-steroidal anti-inflammatory drugs (NSAIDs) with local anesthetics, has shown enhanced potency compared with the usage of local anesthetics alone. However, rare formulations can provide long-term analgesia at a single dose. Herein, bupivacaine (BUP, a local anesthetic) loading poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPB) were coated with meloxicam (MLX, an NSAID) loading lipid bilayer (LPM), forming a core–shell nanosystem (NPB@LPM) to provide enhanced and long-term analgesia to treat postoperative pain. MLX was encapsulated in the lipid shell, which enabled high dose MLX to be released in the first 48 h after surgery to reduce the acute inflammation induced pain. BUP was encapsulated in the PLGA core to provide a long-term release for the nerve block. This nanosystem provided a 7-day (whole recovery cycle) effective analgesia in the Brennan's plantar incision rat model. The tissue reactions of NPB@LPM are benign. This work will provide feasible strategies on designing drug delivery systems for postoperative pain management. [ABSTRACT FROM AUTHOR]

Several chiral reagents including cyclodextrins (CDs) and derivatives, crown ethers, proteins, chiral surfactants, and polymers have been involved in dual-selector systems for enantioseparation of a series of compounds by capillary electrophoresis (CE). In this paper, chondroitin sulfate D-based dual-selector system (CSD/CM-β-CD) was firstly established and investigated for the enantioseparation of six basic racemic drugs in capillary electrophoresis. Compared to the single-selector systems, synergistic effect and significantly improved separations for all tested analytes were observed in CSD/CM-β-CD system. The effect of several parameters, such as buffer pH, chiral selector concentration, and applied voltage, was systematically optimized. Meanwhile, to investigate the possible chiral recognition mechanisms in CSD/CM-β-CD synergistic system, we tried to apply the molecular docking method to simulate the host-guest binding procedures of the polysaccharide-based dual system for the first time. The difference in binding free energy was found to correspond to the chiral selectivity factor. The existence of CSD-CM-β-CD complex may give rise to a higher discriminatory ability against the enantiomers, indicating the synergistic effect in CSD/CM-β-CD system.ᅟ [ABSTRACT FROM AUTHOR]

The authors describe the fabrication of a stationary phase for use in enantioseparation in capillary electrochromatography (CEC). The stationary phase was obtained by covalent immobilization of graphene oxide (GO) on the inner walls of a fused-silica capillary. Methyl-β-cyclodextrin was used as the chiral selector, and the enantiomers were detected by UV absorptiometry. Compared with uncoated fused-silica capillary, obviously improved separation of three tested drug enantiomers was obtained in the GO-polymer coated capillary column (the resolution of Naproxen: 0 → 1.56, Warfarin: 0 → 1.89 and Pranoprofen:0 → 1.51). The effects of buffer pH, type and proportion of organic modifier, concentration of chiral selector and applied voltage were optimized. Molecular modeling was applied to demonstrate the mechanism of enantioseparation, which showed a good agreement with the experimental results. [ABSTRACT FROM AUTHOR]