Antinociceptive activity of Δ9-tetrahydrocannabinol non-ionic microemulsions
- a Neuroscienze PharmaNess S.c.a r.l., c/o Sardegna Ricerche, Edificio 5, Località Piscinamanna, 09010 Pula (Cagliari), Italy
- b Consiglio Nazionale delle Ricerche, Istituto di Tecnologie Biomediche – sezione di Cagliari, c/o Sardegna Ricerche, Edificio 5, Loc. Piscinamanna, 09010 Pula (Cagliari), Italy
Abstract
Δ9-Tetrahydrocannabinol (Δ9-THC), the major psychoactive constituent of Cannabis sativa L., has been widely studied for its potential pharmaceutical application in the treatment of various diseases and disturbs. This sparingly soluble terpeno-phenolic compound is not easy to handle and to be formulated in pharmaceutical preparations.
The aim of this work was to develop a stable aqueous Δ9-THC formulation acceptable for different ways of administration, and to evaluate the therapeutic properties of the new Δ9-THC based preparation for pain treatment. Due to the thermodynamic stability and advantages of microemulsion based systems, the study was focused on the identification of aqueous microemulsion based systems containing Δ9-THC.
Oil in water Δ9-THC microemulsions were individuated through phase diagrams construction, using the non-ionic surfactant Solutol®HS15, being this surfactant acceptable for parenteral administration in human. A selected microemulsion samples containing 0.2 wt% of Δ9-THC, stable up to 52 °C, was successfully assayed on animal models of pain. Significant antinociceptive activity has been detected by both intraperitoneal and intragastric administration of the new Δ9-THC pharmaceutical preparation. The effect has been highlighted in shorter time if compared to a preparation of the same active principle based on previously reported conventional preparation.
Keywords
- Δ9-Tetrahydrocannabinol;
- Phase diagram;
- Microemulsions;
- Pain
Figures and tables from this article:
- Fig. 1. Chemical structure of Δ9-tetrahydrocannabinol.
- Fig. 2. Phase diagram of Δ9-THC/H2O (or saline solution)/HS15 system at 25 °C.
- Fig. 3. Optical micrograph at 25 °C of the Δ9-THC/saline solution/HS15 sample with the following composition (wt%): 8:28:64, characterized by typical maltese crosses of L.L.C. systems.
- Fig. 4. Induced antinociception in the hot-plate (a) and in the tail-flick test (b). Mice were tested after 0.5, 1, 2, 3, and 4 h after administration of Δ9-THC formulations (10 mg/kg i.p.) or corresponding vehicles. Each column represents the mean ± S.E.M. of the %MPE obtained from ten animals. Statistical analysis was carried out using two-way ANOVA followed by Newman–Keuls post hoc test (*P < 0.05).
- Fig. 5. Induced antinociception in the hot-plate (a) and in the tail-flick test (b). Mice were tested after 0.5, 1, 2, 3, and 4 h after administration of Δ9-THC formulations (10 mg/kg i.g.) or corresponding vehicles. Each column represents the mean ± S.E.M. of the %MPE obtained from ten animals. Statistical analysis was carried out using two-way ANOVA followed by Newman–Keuls post hoc test (**P < 0.01).
- Table 1. Thermal stability of Δ9-THC/HS15/SS liquid isotropic samples. The study was carried out from 4.0 to 70.0 °C.Tmax values are the determined upper limit of temperature stability.
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- Table 2. Microemulsion characterization by PCS analysis at 25 °C (all the ratios are expressed as wt/wt ratios).
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- Corresponding author at: Neuroscienze PharmaNess S.c.a r.l., c/o Sardegna Ricerche, Edificio 5, Località Piscinamanna, 09010 Pula (Cagliari), Italy. Tel.: +39 070 924 2025/2026; fax: +39 070 924 2206.
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