PhD Candidate Duquesne University Pittsburgh, Pennsylvania
Effective nose-to-brain delivery of drugs to treat central-nervous-system (CNS) disorders remains a significant challenge due to rapid mucociliary clearance and poor deposition in the olfactory region. This study aimed to develop an optimized PVP-based microparticle platform that works as a shuttle for nose-to-brain drug delivery. Spray-dried microparticles were prepared using PVP K12 and maltodextrin, following a statistical design of experiment (DoE). Optimized DoE conditions were used to prepare drug-loaded (L-DOPA) microparticles. Microparticle characterization showed a DV50 ranging between 16-25 µm, a span ˂1.5. Spray plume angles ranged from 17°-25°, while the % dose delivered from the insufflator varied between 36-74%. In vitro deposition showed that microparticles having DV50≈20 µm preferentially deposited in the olfactory region. These microparticles also exhibited reduced mucociliary transport rates and sustained L-DOPA release over 5h. These findings suggest that the PVP-based microparticle shuttle holds significant promise as a platform for effective nose-to-brain delivery of CNS-targeting drugs.
Learning Objectives:
Upon completion, participants will be able to describe how designing a mucoadhesive microparticle platform enhances intranasal olfactory deposition and prolongs retention time for efficient nose-to-brain delivery of L-DOPA.
Upon completion, participants will be able to identify challenges associated with direct nose-to-brain drug delivery for treating CNS disorders.
Upon completion, participants will be able to list the formulation and technical considerations for developing a solid microparticle platform suitable for direct nose-to-brain drug delivery.
Upon completion, participants will be able to describe why direct nose-to-brain drug delivery is necessary for treating CNS disorders.
Upon completion, participants will be able to relate the importance of particle size for targeting the olfactory region for successful delivery of drugs through the nose-to-brain pathway.
