Blood pressure reduction through brain delivery of nanoparticles loaded with plasmid DNA encoding angiotensin receptor shRNA.

Elevated brain angiotensin II activity plays a key role in the development of neurogenic hypertension. While blood pressure control in neurogenic hypertension has been successfully demonstrated by regulating central angiotensin II activity, current techniques involving cerebrovascular injections of potential therapeutic agents are not suitable for clinical translation. To address this gap, we present the synthesis of dual-functionalized liposomes functionalized with targeting ligand and cell penetrating peptide. Functionalized liposomes were synthesized using the thin film hydration technique and loaded with plasmid DNA encoding shRNA targeted towards Angiotensin II receptors (PEAS), via the post-insertion method. The synthesized liposomes had a cationic surface charge, an average size of 150 nm, and effectively entrapped over 89% of loaded PEAS. These liposomes loaded with PEAS demonstrated biocompatibility and efficient delivery to brain-derived cell lines, resulting in a remarkable reduction of over 70% in receptor expression within 7 days. To assess the therapeutic potential, spontaneously hypertensive rats were administered intravenous injections of functionalized liposomes loaded with PEAS, and the changes in mean arterial pressure were monitored for 45 days. Remarkably, this treatment led to a significant (p < 0.001) reduction in blood pressure of over 30 mmHg compared to saline-treated rats.