1. Chemical and physical characterization of remotely loaded bupivacaine liposomes: comparison between large multivesicular vesicles and small unilamellar vesicles
Rivka Cohen, Ariel Steiner, Hiba Kanaan, Yechezkel Barenholz*. J. Mater. Chem. B, 2013, 1, 4619–4627
Large multivesicular vesicles (LMVV) were prepared as previously described. An ethanolic solution of HSPC100, C16-SPM, and cholesterol in a 3/3/4 mole ratio was hydrated by mixing with 127 mM ammonium sulfate (AS) (285 mOsm-Osmometer 3320, Advanced Instruments, Norwood, MA) to reach a final ethanol concentration of 10% and a phospholipid concentration of
60 mM. The resulting lipid dispersion was exposed to 10 freeze–thaw cycles. A transmembrane gradient of ammonium sulfate (ASliposomes\ASmedium) was used as the remote loading driving force . An AS gradient was created by replacing the ammonium sulfate medium with 150 mM (285 mOsm) NaCl by diafiltration at 4 oC with a Labscale TFF System using a Pellicon XL, 500k polyethersulfone membrane (Millipore Corp., Billerica, MA). Bupivacaine was remotely loaded by mixing LMVV with an aqueous solution of bupivacaine for 1 h at 60 oC, obtaining a final concentration of 20 mM phospholipids and 4.3% (125 mM) bupivacaine. The non-encapsulated drug was removed by diafiltration against 150 mM NaCl. The final Bupisome dispersion was stored in 1% free BUP solution, pH 5.5, at 4 oC.
2. Water-compatible molecularly imprinted polymers for efficient direct injection on-line solid-phase extraction of ropivacaine and bupivacaine from human plasma
Zoe Cobb*, Borje Sellergrenb, Lars I. Anderssona. Analyst, 2007, 132, 1262–1271
The final method was evaluated for its ability to accurately determine ropivacaine and bupivacaine in human plasma. While template leakage from the MIP column was observed this leakage was reduced to below the limit of detection by performing one extraction cycle. This elimination of template bleeding was a direct result of the use of an on-line SPE system, which allowed continual washing of the MIP column. By contrast, in off-line SPE, template bleeding is preserved throughout a number of successive extractions. A small degree of carryover (ca. 1.5%) was observed after injection of samples containing high concentrations of bupivacaine, >100 mmol L-1.
3. Sequestration of drugs using poly(acrylic acid) and alkyl modified poly(acrylic acid) nanoparticles
Soma Chakraborty, P. Somasundaran*. Soft Matter, 2006, 2, 850–854
The nanoparticles under investigation were synthesized inside the reverse microemulsion of Span 80/Tween 80/hexane/water. The extractions of the drugs from bulk media were monitored at pH 7.4 and at 37 uC. It was observed that in 5 minutes each gram of PAA nanoparticles could extract 93 mg of amitriptyline and 73 mg of bupivacaine whereas same amount of AMPAA extracted 83 mg of amitriptyline and 67 mg of bupivacaine. In normal saline amitriptyline extraction by PAA and AMPAA was 81 mg and 68 mg respectively, bupivacaine extraction by unmodified and modified PAA was 62 mg and 51 mg respectively. These exactions are reported for each gram of nanoparticles added.
4. Sustained release of bupivacaine for post-surgical pain relief using core–shell microspheres
Y. Shona Pek, Pemakorn Pitukmanorom, Jackie Y. Ying*. J. Mater. Chem. B,2014, 2,8194–8200
These micro-sphere compacts were then implanted into the parapatellar space in the stifle joint of goats in order to determine their eﬃcacy in releasing and maintaining therapeutic bupivacaine concentrations for 2 weeks in the synovial fluid. Therapeutic doses commonly used are 4 ml h-1 of 0.25% (2.5 mg ml-1) bupivacaine. In addition, as the recommended dosage limit of bupivacaine is 400 mg per day (ref. 25) and excessively high bupivacaine concentrations (0.5%, 5mgml-1) have been shown to be toxic to cartilage and chondrocytes, it was important that burst release did not occur. Therefore, bupivacaine levels in both the synovial fluid as well as the plasma were monitored throughout the 2 week duration of themicrosphere delivery and for an additional 2 weeks to ensure the bupivacaine release from the microspheres had stopped.