Objectives: The present study is aimed to develop poly(D, L-lactide-co-glycolic acid)
(PLGA) nanoparticles (NP) loaded with midazolam (Mdz) for nose to brain delivery.
Materials and Methods: NP were formulated by nanoprecipitation and characterized for z-average,
zeta potential, % drug entrapment and ex vivo drug release. Mdz NP (MNP) were radiolabeled with
technetium-99m. Biodistribution and gamma scintigraphic studies were performed on Sprague-Dawley rats following intranasal
(i.n) and intravenous (i.v) administration to trace the transport of Mdz for nose-to-brain delivery.
Results and Discussion: MNP showed z-average of 164±4.5nm with polydispersity index 0.099±0.02 and zeta potential
of -16.6±2.5mV. Ex vivo drug studies indicated that MNP showed 29±1.2% of permeation upto 4h via sheep nasal mucosa,
whereas Mdz suspension (MS) showed drug release of 83±1.2% within 4h. Comparing i.n administration of MNP,
MS and i.v administration of MS, scintigraphy imaging and Brain/blood uptake ratios indicated higher brain targeting via
i.n administration of MNP.
Conclusion: Results indicated that the i.n MNP could be employed as a non invasive mode of delivery system with improved
drug entrapment, stability and controlled drug release over a period of time.