Karim Mohsen

Abstract

Subarachnoid hemorrhage (SAH) is the leading cause of death in stroke patients who suffer from vasospasms with incidence of 70%. SAH prevents sufficient oxygen supply to the brain causing ischemia and death. FDA approved only nimodipine (NM) for treatment of vasospasm associated with SAH. Nevertheless, NM has poor pharmacokinetic properties, which limit its clinical efficacy. NM is susceptible to first-pass metabolism and has low solubility and thereby poor bioavailability. The objective of this study is to assess the nose-brain pathway in brain targeting of NM-loaded lipid nanocapsules (LNCs) after intranasal administration. Solvent-free phase inversion temperature technique was used to prepare NM-loaded LNCs. Design Expert 7 was used to establish D-optimal mixture design. The model evaluates the impact of individual and combined effects of three independent variables, X1 (Labrafac), X2 (Solutol HS 15), and X3 (water), on responses Y1 (particle size), Y2 (Zeta potential), Y3 (polydispersity index; PDI), Y4 (drug payload), Y5 (entrapment efficiency), Y6, Y7, and Y8 (in vitro drug release after 6, 24, and 48 h, resp.), and Y9 (solubilization capacity). NM-loaded LNC was optimized to increase the NM payload, decrease particle size, and fulfil suitable zeta potential, PDI, and in vitro drug release. The optimized NM-loaded LNC revealed narrow size distribution of PDI of 0.146 ± 0.045, small particle size of 35.94 ± 0.14 nm, 5 mg/mL drug payload, spherical morphology, and appropriate drug release profile initially and over a 3-month period. The in vivo pharmacokinetic assessment of optimized NM-loaded LNC revealed absolute bioavailability of NM in brain (99.5%) and plasma (102.6%) in Wistar rats after intranasal administration of NM-loaded LNCs with reference to the IV administered NM solution. Finally, intranasal administration of NM-loaded LNCs supported safe and effective practice to deliver NM via intranasal route to the brain via systemic pathway attributed with NM BBB enhancement.

Department

Nanotechnology Program

Degree Name

MS in Nanotechnology

Graduation Date

2-1-2018

Submission Date

October 2017

First Advisor

Azzazy, Hassan

Second Advisor

Allam, Nageh

Committee Member 1

Ramadan, Adham

Committee Member 2

Hathout, Rania

Extent

128 p.

Document Type

Master's Thesis

Rights

The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy. The author has granted the American University in Cairo or its agents a non-exclusive license to archive this thesis, dissertation, paper, or record of study, and to make it accessible, in whole or in part, in all forms of media, now or hereafter known.

Institutional Review Board (IRB) Approval

Not necessary for this item

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