Advanced cannabidiol delivery platforms: smart biomaterials, controlled release systems, and 3D-bioprinted therapeutic technologies

Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa L. has gained significant attention in biomedical research due to its broad spectrum of therapeutic properties, including anti-inflammatory, antimicrobial, antioxidant, neuroprotective, and anticancer activities. However, its clinical translation remains limited by poor aqueous solubility, low bioavailability, rapid metabolism, and instability under physiological conditions. To overcome these challenges, advanced drug delivery platforms based on 3D bioprinting technologies have emerged as promising strategies for controlled and site-specific delivery of CBD. This review provides a comprehensive overview of state-of-the-art CBD delivery systems, including polymeric biomaterials such as PLGA, PEG derivatives, chitosan, alginate, and cellulose-based hybrids, which enhance drug stability and enable sustained release profiles. Nano- and microstructured systems, including liposomes, nanoparticles, nanoemulsions, microspheres, and electrospun nanofibers, are discussed for their ability to improve bioavailability and facilitate targeted delivery at the cellular level. Hydrogel-based platforms, particularly injectable and stimuli-responsive systems, are highlighted for their role in localised therapy and tissue engineering applications. Furthermore, the integration of 3D bioprinting technologies enables the fabrication of patient-specific scaffolds and implantable constructs for precision medicine and regenerative therapies. Stimuli-responsive systems, including pH-, temperature-, enzyme-, and externally triggered release platforms, further enhance on-demand drug release in diseased microenvironments. The biomedical applications of CBD-based systems are critically evaluated in antimicrobial therapy, wound healing, tumour-targeted cancer therapy, immunomodulation, microbiome regulation, and regenerative medicine. Finally, this review addresses current translational challenges such as drug loading efficiency, stability issues, scalability, and regulatory barriers, while highlighting future perspectives involving artificial intelligence-guided design, personalised nanomedicine, and advanced biomanufacturing technologies. Overall, CBD-based smart biomaterial platforms represent a highly promising approach for next-generation therapeutic systems with improved efficacy, safety, and clinical potential.