Intrathecal Administration of Liposomal Morphine in a Mouse Model

Antinociceptive/Anti-Edema Effects of Liposomal Morphine during Acute Inflammation of the Rat Paw

“…The prolonged anti-edema and antinociceptive effects of MS-LP could be explained by the slow release of morphine from liposomes demonstrated in the in vitro experiments ( fig. 1) and a delayed rate of metabolism [3,4]. Thus, during inflammation MS-LP had an enhanced anti-edema effect, while the antinociceptive potency was of a lesser magnitude when compared to MS-F. We do not have a definite explanation for the effects of MS-LP during inflammation.…”

“…In the treatment of pain, liposomal local anesthetics have been widely investigated both in animals [1] and man [2] showing that encapsulation induces an increase in the duration of antinociception and a decrease of systemic toxicity. Using opioids, animal studies have demonstrated that liposomal morphine (MS-LP) administered systemically [3] or spinally [4] produces prolonged analgesia with decreased toxicity when compared to the free morphine (MS-F).…”

Extended-Duration Analgesia: Update on Microspheres and Liposomes

“…In vitro dialysis of morphine-encapsulated liposomes (M-L) shows sustained release, with 50% of plain morphine appearing in the dialysate within 10 minutes, as compared with 24 hours for M-L. 37 When administered in the lumbar intrathecal space in mice, morphine stores remained concentrated within the lower spinal segments, in contrast to the wider spinal seg- mental distribution and rapid clearance observed with plain morphine. 45 Liposomal encapsulation of alfentanil resulted in reduced plasma concentration as compared with subarachnoid injection of plain alfentanil in rats. 44 Alfentanil, which normally undergoes rapid rostral redistribution, also exhibited delayed peak plasma levels, reduced rostral spread, and higher spinal cord levels when encapsulated with liposomes.…”

“…The ideal liposome has the ability to encapsulate high drug concentrations, be cleared slowly from the injection site, and maximize active drug release. 39 Plain liposomes have no inherent pharmacologic activity 37,[43][44][45] and are incapable of crossing the blood-brain barrier or blood-nerve barrier. 46 Pharmacodynamic effects occur after active drug release from the liposomal matrix, rather than from neural uptake of the combined liposomal moiety.…”

Determination of morphine 3-esters in rabbit plasma by high-performance liquid chromatography with ultraviolet detection

“…In vitro experiments with morphine 3-esters showed that the rate of ester hydrolysis (i.e. release of morphine) depends on the steric arrangements of the acid moiety used for esterification (Mignat et al, 1996), suggesting that the duration of the action of morphine can be prolonged administrating it as an ester pro-drug (Grant et al, 1995).…”