[Preliminary study on brain-targeted drug delivery via inner ear]

Area of Science:

• Neuroscience
• Pharmacology
• Biotechnology

Background:

• The brain presents a significant challenge for drug delivery due to the blood-brain barrier.
• Novel drug delivery routes are needed to effectively target brain tissues.

Purpose of the Study:

• To investigate the feasibility of delivering drugs to the brain via the inner ear.
• To evaluate dexamethasone acetate-loaded solid lipid nanoparticles (SLN) for enhanced brain drug delivery.

Main Methods:

• Dexamethasone acetate (DA)-loaded SLN were prepared using Compritol 888 ATO.
• HPLC assays were developed for DA, dexamethasone sodium phosphate (DSP), and dexamethasone (Dex).
• DA-loaded SLN and DSP solutions were administered via intratympanic injection (IT) or intravenous injection (IV), with perilymph (PL) and cerebrospinal fluid (CSF) analysis.

Main Results:

• Intratympanic administration of DA-loaded SLN or DSP solution resulted in significantly higher dexamethasone concentrations in CSF compared to intravenous injection.
• IT DA-loaded SLN increased the area under the curve (AUC) of dexamethasone in CSF by 13-fold and extended the mean residence time (MRT) by 19-fold compared to solution.
• IT administration of SLN reduced dexamethasone levels in perilymph by 76% compared to the solution, suggesting reduced cochlear exposure.

Conclusions:

• Intra-cochlear administration, particularly using dexamethasone acetate-loaded SLN, is a feasible and promising strategy for brain-targeted drug delivery.
• This novel route bypasses conventional barriers, offering enhanced drug exposure in the brain while potentially minimizing peripheral side effects.