Nose to Brain Delivery of Midazolam Loaded PLGA Nanoparticles: In Vitro and In Vivo Investigations

Author(s): Deepak Sharma, Rakesh Kumar Sharma, Aseem Bhatnagar, Dhruv K. Nishad, Thakuri Singh, Reema Gabrani, Sanjeev K. Sharma, Javed Ali, Shweta Dang.

Journal Name: Current Drug Delivery

Volume 13 , Issue 4 , 2016

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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±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.

Keywords: Biodistribution, ex vivo, intranasal, nanoprecipitation, polymeric nanoparticles, radiolabeling, scintigraphy.

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Article Details

Year: 2016
Page: [557 - 564]
Pages: 8
DOI: 10.2174/1567201812666150507120124
Price: $58

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