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Since the early 2000s, herbal mixtures containing synthetic cannabinoids (SCs), broadly known as Spice/K2, have been marketed as a legal marijuana surrogate and have become very popular among adolescents. Adolescence is a critical period of development, which is associated with an increased vulnerability to the central effects of drugs. Despite growing concerns about the negative effects of the use of SCs, newly synthetized compounds are increasingly detected in drugs seized by the authorities, posing a serious threat to public health. 5F-MDMB-PICA has been recently detected and classified as a highly potent agonist of CB1 and CB2 cannabinoid receptors. Here, we first investigated the rewarding properties of 5F-MDMB-PICA in C57BL/6 adolescent and adult mice by in vivo brain microdialysis. Data showed that acute administration of a selected dose of 5F-MDMB-PICA (0.01 mg/kg i.p.) stimulates the release of dopamine in the nucleus accumbens shell of adolescent, but not of adult, mice. To further investigate the consequences of repeated exposure to this dose of 5F-MDMB-PICA, a separate group of adolescent mice was treated for 14 consecutive days and evaluated for behavioral abnormalities at adulthood, starting from 7 days after drug discontinuation. Data showed that this group of adult mice displayed an anxiety-like and compulsive-like state as revealed by an altered performance in the marble burying test. Our study suggests an alarming vulnerability of adolescent mice to the effects of 5F-MDMB-PICA. These findings provide a useful basis for understanding and evaluating both early and late detrimental effects that may derive from the use of SCs during adolescence.

No abstract

Needle-free liquid jet injectors are medical devices used to administer pharmaceutical solutions through the skin. Jet injectors generate a high-speed stream of liquid medication that can puncture the skin and deliver the drug to the underlying tissues. In this work, we investigated the feasibility of using liquid jet injectors to administer nanosuspensions, assessing the impact of the jet injection on their pharmaceutical and physicochemical properties. For this purpose, the model drug diclofenac was used to prepare a set of nanosuspensions, stabilized by poloxamer 188, and equilibrated at different pHs. The hydrodynamic diameter and morphology of the nanocrystals were analyzed before and after the jet injection across porcine skin in vitro, together with the solubility and release kinetics of diclofenac in a simulated subcutaneous environment. The efficacy of the jet injection (i.e., the amount of drug delivered across the skin) was evaluated for the nanosuspension and for a solution, which was used as a control. Finally, the nanosuspension was administered to rats by jet injector, and the plasma profile of diclofenac was evaluated and compared to the one obtained by jet injecting a solution with an equal concentration. The nanosuspension features were maintained after the jet injection in vitro, suggesting that no structural changes occur upon high-speed impact with the skin. Accordingly, in vivo studies demonstrated the feasibility of jet injecting a nanosuspension, reaching relevant plasma concentration of the drug. Overall, needle-free jet injectors proved to be a suitable alternative to conventional syringes for the administration of nanosuspensions.

No abstract