Ts such as paclitaxel or camptothecin hinders their application and complicates direct parenteral administration. In the case of cannabinoids, several pharmaceutical preparations have been developed and approved for cannabinoid administration including oral capsules of THC (MarinolH, Unimed Pharmaceuticals Inc.) and of its synthetic analogue nabilone (CesametH, Meda Pharmaceuticasl) and an oromucosal spray of standardized cannabis extract (SativexH, GW Pharmaceuticals). These formulations have been approved for several clinical applications [5,20]. Specifically, MedChemExpress FCCP cannabinoids are well-known to exert palliative effects in cancer patients [5,20]. The best-established use is the inhibition of chemotherapy-induced nausea and vomiting [5,6] (MarinolH and CesametH). Cannabinoids also inhibit pain, and SativexH has been already approved in Canada and is currently subject of large-scale Phase III clinical trials for managing cancer-associated pain. However, from the perspective of the utilization of cannabinoid-based medicines as antineoplastic agents, one of the issues that needs to be clarified is whether systemic administration of cannabinoids allows reaching effective concentrations of these highly lipid soluble agents [21] at the tumor 
site without enhancing undesired side affects [5,6]. Local administration of polymeric implants for interstitial sustained release of anti-neoplasic agents allows enhancing the concentration of anticancer active substances in the proximity of the tumour [22?6] and could be an alternative strategy to systemic delivery at least for certain types of cancer. The aim of the present study was therefore to evaluate the antitumor efficacy of biodegradable polymeric microparticles allowing the controlled release of the phytocannabinoids THC and CBD. Our findings show that administration of cannabinoid-loaded microparticles reduces the growth of glioma xenografts supporting that this method of administration could be exploited for the design of cannabinoid-based anticancer treatments.Spain). All chemicals and reagents were used as received. In order to avoid cannabinoid binding to labware, materials were pretreated with SigmacoteH.Cannabinoid solutionFor in vivo administration to mice, cannabinoid solutions were prepared at 1 (v/v) DMSO 
in 100 mL of PBS supplemented with 5 mg/mL of 18204824 emulsion solvent evaporation technique. Briefly, 50 mg of drug and 500 mg of polymer were dissolved in 5 mL of methylene chloride. Subsequently, the organic solution was poured onto 250 mL of a 0.5 PVA aqueous solution under stirring at 3000 rpm for 6 min. The resulting O/W emulsion was then stirred for 3 h to evaporate the organic solvent. Finally, the resulting MPs were washed with distilled water, filtrated (0.45 mm membrane filters) and freeze-dried. Vitamin E acetate (5 ) was added to the organic solution when preparing THC-loaded MPs in order to avoid THC oxidation. Blank MPs were prepared using the same procedure but without adding cannabinoids.Microparticles morphology and size distributionScanning electron microscopy (JSM 6400, Tokyo, Japan) was used to evaluate the shape and the surface morphology of the blank, CBD- or THC-loaded PCL MPs. Particle size distribution was analyzed using a MicrotracH SRA 150.Ts such as paclitaxel or camptothecin hinders their application and complicates direct parenteral administration. In the case of cannabinoids, several pharmaceutical preparations have been developed and approved for cannabinoid administration including oral capsules of THC (MarinolH, Unimed Pharmaceuticals Inc.) and of its synthetic analogue nabilone (CesametH, Meda Pharmaceuticasl) and an oromucosal spray of standardized cannabis extract (SativexH, GW Pharmaceuticals). These formulations have been approved for several clinical applications [5,20]. Specifically, cannabinoids are well-known to exert palliative effects in cancer patients [5,20]. The best-established use is the inhibition of chemotherapy-induced nausea and vomiting [5,6] (MarinolH and CesametH). Cannabinoids also inhibit pain, and SativexH has been already approved in Canada and is currently subject of large-scale Phase III clinical trials for managing cancer-associated pain. However, from the perspective of the utilization of cannabinoid-based medicines as antineoplastic agents, one of the issues that needs to be clarified is whether systemic administration of cannabinoids allows reaching effective concentrations of these highly lipid soluble agents [21] at the tumor site without enhancing undesired side affects [5,6]. Local administration of polymeric implants for interstitial sustained release of anti-neoplasic agents allows enhancing the concentration of anticancer active substances in the proximity of the tumour [22?6] and could be an alternative strategy to systemic delivery at least for certain types of cancer. The aim of the present study was therefore to evaluate the antitumor efficacy of biodegradable polymeric microparticles allowing the controlled release of the phytocannabinoids THC and CBD. Our findings show that administration of cannabinoid-loaded microparticles reduces the growth of glioma xenografts supporting that this method of administration could be exploited for the design of cannabinoid-based anticancer treatments.Spain). All chemicals and reagents were used as received. In order to avoid cannabinoid binding to labware, materials were pretreated with SigmacoteH.Cannabinoid solutionFor in vivo administration to mice, cannabinoid solutions were prepared at 1 (v/v) DMSO in 100 mL of PBS supplemented with 5 mg/mL of 10457188 bovine serum albumin. No significant influence of the vehicle was observed on any of the variables determined in this study.Microparticles preparationBiodegradable polymeric microparticles (MPs) were prepared by the oil-in-water 18204824 emulsion solvent evaporation technique. Briefly, 50 mg of drug and 500 mg of polymer were dissolved in 5 mL of methylene chloride. Subsequently, the organic solution was poured onto 250 mL of a 0.5 PVA aqueous solution under stirring at 3000 rpm for 6 min. The resulting O/W emulsion was then stirred for 3 h to evaporate the organic solvent. Finally, the resulting MPs were washed with distilled water, filtrated (0.45 mm membrane filters) and freeze-dried. Vitamin E acetate (5 ) was added to the organic solution when preparing THC-loaded MPs in order to avoid THC oxidation. Blank MPs were prepared using the same procedure but without adding cannabinoids.Microparticles morphology and size distributionScanning electron microscopy (JSM 6400, Tokyo, Japan) was used to evaluate the shape and the surface morphology of the blank, CBD- or THC-loaded PCL MPs. Particle size distribution was analyzed using a MicrotracH SRA 150.
