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

Abstract

Several approaches have been utilised to deliver therapeutic nanoparticles inside the brain but rendered by certain limitation such as active efflux, non-stability, toxicity of the nanocarrier, transport, physicochemical properties and many more. In this context use of biocompatible nano carriers is currently investigated. We herein present the hypothesis that the nucleoside-lipid based conjugates (nucleolipids) which are biocompatible in nature and have molecular recognition can be tuned for improved permeation across blood–brain barrier (BBB). In this work, a di-C15-palmitoyl-ketal nucleolipid nanoparticle bearing an acyclic chelator has been formulated, radiolabeled with ^99mTc and evaluated for in vivo fate using SPECT imaging. The mean particle size of particles was 113 nm and found to be nontoxic as depticted through haemolytic assay (2.33% erythrocyte destruction) and 75 ± 0.3% HEK(Human Embryonic Kidney) cells survived at 72 h as depicted in SRB (Sulforhodamine B) toxicity assay. The encapsulation efficiency (68 ± 2.75%) and drug loading capacity (22 ± 1.8%.) was calculated for nanoparticles using Methotrexate as model anti-cancer drug. The mathematical models indicate fickian release with a release constant K_H = 20.70. With 98 ± 0.75% radiolabelling efficiency and established in vitro stability, nanoparticles showed brain uptake in normal mice as 0.91 times in comparison to BBB compromised mice (1.6% ± 0.03 ID/g)indicating higher brain uptake with rapid clearance as depicted through blood kinetics.