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

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

Volume: 13 Issue: 4

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

Affiliation:

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

Abstract: 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.

Cite this article as:

Sharma Deepak, Kumar Sharma Rakesh, Bhatnagar Aseem, K. Nishad Dhruv, Singh Thakuri, Gabrani Reema, K. Sharma Sanjeev, Ali Javed and Dang Shweta, Nose to Brain Delivery of Midazolam Loaded PLGA Nanoparticles: In Vitro and In Vivo Investigations, Current Drug Delivery 2016; 13 (4) . https://dx.doi.org/10.2174/1567201812666150507120124