Biodegradable polymer sheets implanted sub-durally may be useful for intracranial drug delivery
Purpose: Many drugs used for neurological disorders have a narrow effective dose range. This is due to the fact that the majority are administered orally or intravenously, resulting in toxicity to many peripheral organs at higher doses. Direct intracranial administration of neurological drugs has been shown to reduce the minimum effective dose, whilst simultaneously reducing peripheral side effects (Serralta et al., 2006). We therefore sought a mechanism for long-term administration of drugs to the cerebral cortex, and investigated the possibility of using sub-dural sheets of biodegradable polymers as to achieve this.
Method: Biocompatible polymers such as poly-lactide (PLA) and copolymers of poly-lactide (PLA) and poly-lactide-co-glycolide (PLGA) were drop-cast to form sheets of varying thicknesses. These were implanted sub-durally over the motor cortex of Sprague-Dawley rats (n=3 per group) to confirm the biocompatibility of these polymers, and to examine the cellular and structural consequences of the implantation. The degradation rates of the sheets were also examined, in vitro. This study was approved by the St Vincent’s Hospital Animal Ethics Committee and run in accordance with the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes (2004).
Results: PLA or PLA:PLGA sheets implanted sub-durally were well tolerated by the rat brain. The sheets endure within the central nervous system over time periods which make them useful for long-term drug delivery.
Conclusion: Sub-dural sheets based on biodegradable polymers represent a viable candidate for long-term intracranial drug delivery.