3D-printed long-acting implants for risperidone delivery using VAT photopolymerisation: a potential alternative for schizophrenia treatment.

Chronic conditions are increasingly prevalent worldwide, with the oral route being the most common for drug administration. However, limitations such as low bioavailability and patient nonadherence can result in complications that affect the patient's quality of life and increase healthcare costs. In schizophrenia, up to 75% of patients discontinue treatment within 18 months, raising risks of relapse, hospitalization and suicide. Therefore, sustained drug delivery systems offer a promising alternative. To this end, different long-acting subcutaneous implants, loaded with risperidone (RIS) were prepared through the variation of polymers and drug loading, by VAT photopolymerisation 3D-printing technique. The obtained implants were comprehensively characterized in terms of morphology, swelling and release profile. Among these, two polyethylene glycol diacrylate (PEGDA 700)-based implants, one incorporating polylactic acid-polyurethane (PLA-PUA) (R2L2P76) and the other without (R2P78), showed promising in vitro release characteristics (up to 300 and 100 days, respectively) and therefore were selected as lead formulations for further investigation. R2P78 and R2L2P76 lead implants were further characterised using different techniques such as thermal analysis and infrared spectroscopy. Finally, their cytotoxicity was tested in 3 T3 murine fibroblasts showing biocompatibility and insignificant effect on cell viability. This study demonstrates the feasibility of preparing versatile subcutaneous implants via VAT photopolymerisation 3D-printing, that can be customised to patients' needs at the point of care, as a promising alternative for the sustained delivery of RIS. Such long-acting implants have the potential for increasing patient compliance and improving therapeutic efficiency for schizophrenia treatment.