Apolipoprotein E3 functionalized mesoporous silica nanoparticles for targeted and enhanced therapeutic efficacy of Levetiracetam in brain tumor-associated epilepsy: Insights into brain uptake, biodistribution and pharmacokinetic behavior.

in International journal of biological macromolecules by Mansi Athalye, Mehul Chorawala, Abhilasha Sharma, Sandip Patel, Rashmin Patel, Mrunali Patel

TLDR

  • Researchers developed a novel formulation of LVM-loaded mesoporous silica nanoparticles conjugated with ApoE3 for enhanced brain-targeting in patients with brain-tumors and epilepsy.

Abstract

Epilepsy affects approximately 20-40 % of patients with brain-tumors, significantly impacting their quality of life and overall survival rates. To address this, Levetiracetam (LVM) has emerged as effective treatment option due to minimal negative interactions with other medications and reduced side-effects. However, its hydrophilic nature necessitates high doses and frequent administration, which can lead to drug resistance and hinder the clinical response to therapy. The present research focuses on developing a novel formulation of LVM-loaded mesoporous silica nanoparticles(LVM-MSN) conjugated with Apolipoprotein E3(ApoE3) for enhanced brain-targeting. LVM-MSN were prepared using the calcination method after optimizing different synthesis parameters. Chitosan was employed as capping agent to form LVM-Chito-MSN, which was characterized using zeta potential, XRD, FE-SEM, and TEM study. Further, LVM-Chito-MSN was functionalized by ApoE3 as brain-targeting ligand through direct coating approach(ApoE3@LVM-Chito-MSN). In-vivo pharmacokinetic study and biodistribution study indicated an impressive 3-fold increase in brain-uptake of ApoE3@LVM-Chito-MSN, with reduced distribution to other organs compared to LVM solution. The hemolysis study and histological examination of major organs indicated safety of the formulation. Consequently, functionalization of MSN with ApoE3 represents promising strategy for enhanced brain targeting, which could lead to improved patient compliance and better overall survival rates for patients suffering from brain tumor-related epilepsy.

Overview

  • The study aimed to develop a novel formulation of Levetiracetam (LVM)-loaded mesoporous silica nanoparticles (LVM-MSN) conjugated with Apolipoprotein E3 (ApoE3) for enhanced brain-targeting in patients with brain-tumors and epilepsy.
  • The researchers optimized the synthesis parameters and characterized the LVM-MSN using various techniques, including zeta potential, XRD, FE-SEM, and TEM.
  • The primary objective was to improve patient compliance and overall survival rates by developing a more effective and safer treatment option for patients with brain-tumor related epilepsy.

Comparative Analysis & Findings

  • The in-vivo pharmacokinetic study and biodistribution study showed a 3-fold increase in brain-uptake of ApoE3@LVM-Chito-MSN compared to LVM solution.
  • The distribution of ApoE3@LVM-Chito-MSN to other organs was reduced compared to LVM solution.
  • The hemolysis study and histological examination of major organs indicated the safety of the formulation.

Implications and Future Directions

  • The functionalization of MSN with ApoE3 represents a promising strategy for enhancing brain-targeting, which could lead to improved patient compliance and better overall survival rates.
  • Future studies could focus on further optimizing the synthesis parameters and characterizing the nanoparticles to improve their biocompatibility and efficacy.
  • The potential of ApoE3@LVM-Chito-MSN as a treatment option for brain-tumor related epilepsy warrants further evaluation in clinical trials.
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