Towards an effective, needle-based delivery device for Parkinson's disease: a simulation study on the impact of needle diameter

Recently, several therapies have emerged for Parkinson’s disease, a challenging neurodegenerative disorder. However, clinical translation is restricted, partially due to limitations in delivering therapeutics to the Central Nervous System (CNS)which cannot be reached by systemic administration. An alternative method, that bypasses the blood brain barrier and offers high-concentrated deposition in the diseased region, is intrastriatal delivery of a cell-loaded in situ forming collagen hydrogel. However, this strategy has disadvantages, including neuroimmune response and haemorrhage. To minimize these responses, an optimised medical device should be designed. Of main consideration is the volume dispensed and the needle dimensions. Current approaches use 18-20-Gaugediameter needles and multiple cranial penetrations. Additionally, fluid forces acting on cells may lead to cell disruption and death. This study aims to develop a novel device for the effective delivery of a cell-loaded in situ forming collagen hydrogel to the CNS. A simulation study on constricted channels representing the needle was performed to gain insight into the optimal needle diameter.