Development of amphiphilic self-assembled nucleolipid as BBB targeting probe based on SPECT

Area of Science:

• Nanotechnology
• Biomedical Engineering
• Pharmacology

Background:

• Delivering therapeutics to the brain is challenging due to the blood-brain barrier (BBB).
• Existing nanoparticle delivery systems face limitations like toxicity and poor stability.
• Biocompatible nanocarriers are being explored for enhanced brain drug delivery.

Purpose of the Study:

• To hypothesize and validate nucleoside-lipid based conjugates (nucleolipids) for improved blood-brain barrier (BBB) permeation.
• To formulate and characterize novel nucleolipid nanoparticles for potential brain targeting.
• To evaluate the in vivo fate and brain uptake of radiolabeled nucleolipid nanoparticles.

Main Methods:

• Formulation of a di-C15-palmitoyl-ketal nucleolipid nanoparticle.
• Radiolabeling with technetium-99m (99mTc) and in vivo evaluation using SPECT imaging.
• Assessment of nanoparticle toxicity (hemolytic and SRB assays), stability, encapsulation efficiency, and drug release kinetics.

Main Results:

• Nucleolipid nanoparticles (113 nm) exhibited low toxicity (2.33% erythrocyte destruction, 75% HEK cell survival).
• High encapsulation efficiency (68%) and drug loading (22%) were achieved with Methotrexate.
• SPECT imaging demonstrated significant brain uptake in mice, with higher uptake in normal mice compared to BBB-compromised mice, indicating efficient BBB penetration and rapid clearance.

Conclusions:

• Nucleolipid nanoparticles are biocompatible, non-toxic, and stable nanocarriers.
• These nanoparticles show potential for enhanced drug delivery across the blood-brain barrier.
• Further research into nucleolipid nanoparticles could lead to improved treatments for neurological disorders.