Journal
CURRENT DRUG DELIVERY
Volume 13, Issue 4, Pages 557-564Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1567201812666150507120124
Keywords
Biodistribution; ex vivo; intranasal; nanoprecipitation; polymeric nanoparticles; radiolabeling; scintigraphy
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Funding
- Department of Biotechnology, Government of India (DBT) [BT/PR1891/MED/30/626/2011]
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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 perpendicular to 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.
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