Enhanced Brain Delivery via Intranasal Administration of Carbamazepine Loaded Solid Lipid Nanoparticles: Optimization, Pharmacokinetic Analysis, In-vitro, and In-vivo Drug Release Study.

Abstract

Background: Carbamazepine (Cbz) is the first-line drug for epileptic seizures but exhibits fluctuation at the plasma level and side effects after oral administration.To overcome these problems, Cbz should be targeted directly into the brain. Therefore, the current experimental design was aimed to formulate and optimize the Cbz containing solid lipid nanoparticles (SLNs) for brain delivery via intranasal administration to get rid of oral complications associated with Cbz.

Methods: A full factorial design was performed to evaluate the effect of variables (X1 lipid concentration, X2 surfactant concentration, and X3 sonication time) on the response variables (size of nanoparticles, entrapment efficiency, and drug release). A two-level, three-factor design was employed herewith, and eight formulations were developed. Further, the formation of Cbz containing SLNs was characterized by compatibility, particle size, entrapment efficiency, and drug release with the support of Fourier Transform Infra-Red (FTIR), Zeta sizer, Transmission Electron Microscopy (TEM), Ultra-violet (U.V.), and High-Performance Liquid Chromatography (HPLC).

Results: All eight formulations were characterized through particle size, entrapment efficiency, and invitro drug release performance. Out of eight characterized formulations, SN1 showed the most promising results, including particle size of 210 ± 2.14 nm, entrapment efficiency of 42.1 ± 1.09%, and drug release of 61.3 ± 2.02% and considered an optimized batch. Additionally, the optimized batch SN1was further evaluated for an in-vivo study on male Wistar Rats.

Conclusion: The study revealed that a high amount of drug was reached into the brain through intranasal administration compared to the intravenous route. Therefore, it can minimize the unwanted side effects of the Cbz associated with oral administration. The formulation SN1 possesses an excellent drug targeting efficiency of 3.014. Finally, the current experimental work concluded that there is a direct pathway from the intranasal route to the brain. This delivery system can be beneficial for directly delivering CNS-active drugs into the brain.