3D-printed cannabidiol hollow suppositories for treatment of epilepsy.

Cannabidiol (CBD) is widely used to alleviate the syndromes of epilepsy. However, the marketed oral CBD formulation has the prominent first-pass effect. Here, a cannabidiol-loaded hollow suppository (CHS) was developed using three-dimensional (3D) printing technology. CHS was assembled with an inner supporting spring and an outer CBD-loaded curved hollow shell. The spring was prepared using fused deposition modeling 3D printing with thermoplastic urethane filaments followed by splitting. The shell was prepared with a 3D-printed metal mold filled with the mixture of CBD, polyvinyl alcohol, and polyethylene glycol. CHS slowly in vitro released CBD for 5 h and achieved the systemic delivery of CBD. The high in vitro and in vivo safety of CHS was demonstrated. Epilepsy rat models were established by lithium-pilocarpine dosing. Locally administered CHS greatly alleviated the damage to brains and reduced inflammation. Moreover, CBD obviously improved the abundance and composition of gut microbiota and the abundance of beneficial bacteria, including Lachnoclostridium and Akkermansia. Personalized CHS is a promising medication for the treatment of epilepsy.