Thymoquinone (TQ) is a water-insoluble natural compound isolated from Nigella sativa that has demonstrated promising chemotherapeutic activity. The purpose of this study was to develop a polymeric nanoscale formulation for TQ to circumvent its delivery challenges. TQ-encapsulated nanoparticles (NPs) were fabricated using methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) copolymers by the nanoprecipitation technique. Formulation variables included PCL chain length and NP architecture (matrix-type nanospheres or reservoir-type nanocapsules). The formulations were characterized in terms of their particle size, polydispersity index (PDI), drug loading efficiency, and drug release. An optimized TQ NP formulation in the form of oil-filled nanocapsules (F2-NC) was obtained with a mean hydrodynamic diameter of 117 nm, PDI of 0.16, about 60% loading efficiency, and sustained in vitro drug release. The formulation was then tested in cultured human cancer cell lines to verify its antiproliferative efficacy as a potential anticancer nanomedicine. A pilot pharmacokinetic study was also carried out in healthy mice to evaluate the oral bioavailability of the optimized formulation, which revealed a significant increase in the maximum plasma concentration (Cmax) and a 1.3-fold increase in bioavailability compared to free TQ. Our findings demonstrate that the versatility of polymeric NPs can be effectively applied to design a nanoscale delivery platform for TQ that can overcome its biopharmaceutical limitations.

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Background: Chronic exposure to cigarette smoke produces neuroinflammation and long-term changes in neurotransmitter systems, especially glutamatergic systems.Objective: We examined the effects of cigarette smoke on astroglial glutamate transporters as well as NF-κB expression in mesocorticolimbic brain regions, prefrontal cortex (PFC) and nucleus accumbens (NAc). The behavioral consequences of cigarette smoke exposure were assessed using open field (OF) and light/dark (LD) tests to assess withdrawal-induced anxiety-like behavior.Methods: Sprague-Dawley rats were randomly assigned to five experimental groups: a control group exposed only to standard room air, a cigarette smoke exposed group treated with saline vehicle, two cigarette smoke exposed groups treated with acetylsalicylic acid (ASA) (15 mg/kg and 30 mg/kg, respectively), and a group treated only with ASA (30 mg/kg). Cigarette smoke exposure was performed for 2 h/day, 5 days/week, for 31 days. Behavioral tests were conducted weekly, 24 h after cigarette smoke exposure, during acute withdrawal. At the end of week 4, rats were given either saline or ASA 45 min before cigarette exposure for 11 days.Results: Cigarette smoke increased withdrawal-induced anxiety, and 30 mg/kg ASA attenuated this effect. Cigarette smoke exposure increased the relative mRNA and protein expression of nuclear factor ĸB (NFĸB) in PFC and NAc, and ASA treatment reversed this effect. Also, cigarette smoke decreased the relative mRNA and protein expression of glutamate transporter1 (GLT-1) and the cystine-glutamate transporter (xCT) in the PFC and the NAc, while ASA treatment normalized their expression.Conclusion: Cigarette smoke caused neuroinflammation, alterations in glutamate transporter expression, and increased anxiety-like behavior, and these effects were attenuated by acetylsalicylic acid treatment.

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