Abstract
Morphine is thoroughly used for pain control; however, it has a high addictive potential. Opioid liposome formulations produce controlled drug release and have been thoroughly tested for pain treatment although their role in addiction is still unknown. This study investigated the effects of free morphine and morphine encapsulated in unilamellar and multilamellar liposomes on antinociception and on the expression and extinction of the positive and negative memories associated with environmental cues. The hot plate test was used to measure central pain. The rewarding effects of morphine were analyzed by the conditioned-place preference (CPP) test, and the aversive aspects of naloxone-precipitated morphine withdrawal were evaluated by the conditioned-place aversion (CPA) paradigm. Our results show that encapsulated morphine yields prolonged antinociceptive effects compared with the free form, and that CPP and CPA expression were similar in the free- or encapsulated-morphine groups. However, we demonstrate, for the first time, that morphine encapsulation reduces the duration of reward and aversive memories, suggesting that this technological process could transform morphine into a potentially less addictive drug. Morphine encapsulation in liposomes could represent a pharmacological approach for enhancing extinction, which might lead to effective clinical treatments in drug addiction with fewer side effects.
Highlights
Pain is one of the most common symptoms of disease, causing suffering in millions of persons every day
The vesicle size distribution for pegylated unilamellar liposomes (PEG-L) tested was unimodal with an intensity-average size of 120.45 ± 10.53 nm, whereas multilamellar vesicles (MLVs) showed a bimodal curve with higher heterogeneity
In this study free morphine was compared with MLV and PEG-L, and in both liposomes formulations, we used remote loading to obtain a high level of drug entrapment
Summary
Pain is one of the most common symptoms of disease, causing suffering in millions of persons every day. Alleviating pain has always been one of the main objectives of pharmacological research and finding analgesic drugs with reduced secondary effects is of special interest. As other opiates, is thoroughly used for pain control in many situations, it has drawbacks, one of the main ones being possible addiction. New advanced-formulation designs can be used with analgesic drugs to reduce dosing schedules, provide more consistent plasma levels, improve drug absorption, and speed up the therapeutic action beginning. In this sense, opioid liposome formulations, which are known to produce controlled drug release, have been widely tested for decades for pain treatment (Kim et al, 1996)
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