Liposome-Encapsulated Morphine Affords a Prolonged Analgesia While Facilitating Extinction of Reward and Aversive Memories

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.

Mesoporous Polydopamine Nanoparticles Attenuate Morphine Tolerance in Neuropathic Pain Rats by Inhibition of Oxidative Stress and Restoration of the Endogenous Antioxidant System

“…The pharmacokinetic studies were done using the previously reported protocols with minor changes [ 36 ]. Rats received one intraperitoneal (i.p.)…”

Controlling lamellarity and physicochemical properties of liposomes prepared using a microfluidic device

“…Comparisons of the physicochemical properties and effects on drug activity between uni-and multi-lamellar liposomes have been reported. [15][16][17][18][19][20][21] Generally, liposomes are classified according to their preparation method. For example, liposomes prepared using a lipid thin-film hydration method tend to form multi-lamellar vesicles.…”

Liposomes as Multifunctional Nano-Carriers for Medicinal Natural Products

“…However, it is highly addictive because the high concentration accesses the central nervous system, which normally occurs when the free form is administrated. Liposome formulations prolonged the analgesic effect and reduce addiction ( Gómez-Murcia et al, 2019 ). The formulation also significantly enhanced antitransit effects of morphine ( Pol et al, 1996 ).…”