IGF-II-Conjugated Nanocarrier for Brain-Targeted Delivery of p11 Gene for Depression

• Published in: AAPS PharmSciTech 2019-02, Vol.20 (2), p.50-50, Article 50
• Main Authors: Gandhi, Manit, Bhatt, Priyanka, Chauhan, Gaurav, Gupta, Sarita, Misra, Ambikanandan, Mashru, Rajashree
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Brain - metabolism; Cell Line, Tumor; Cell Survival - physiology; Cell-Penetrating Peptides - administration & dosage; Cell-Penetrating Peptides - genetics; Cell-Penetrating Peptides - metabolism; Depression - genetics; Depression - metabolism; Depression - therapy; Gene Targeting - methods; Gene Transfer Techniques; Genetic Therapy - methods; Humans; Insulin-Like Growth Factor II - administration & dosage; Insulin-Like Growth Factor II - genetics; Insulin-Like Growth Factor II - metabolism; Liposomes - chemistry; Male; Mice; Nanoparticles - administration & dosage; Nanoparticles - metabolism; Pharmacology/Toxicology; Pharmacy; Rats; Rats, Sprague-Dawley; Research Article; Theme: Translational Multi-Disciplinary Approach for the Drug and Gene Delivery Systems
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-018-1206-x

Gene therapy involving p11 cDNA has been thought to be a futuristic approach for the effective management of depression as the existing treatment regimen presents many issues regarding late onset of action, patient withdrawal and their side effects. For the effective transfection of p11 gene intracellularly, two cationic lipids based on phospholipid DOPE conjugated to basic amino acids histidine and arginine were synthesised, used for liposome formulation and evaluated for their ability as gene delivery vectors. They were further converted using IGF-II mAb into immunoliposomes for CNS targeting and mAb conjugation to liposomes were characterised by SDS-PAGE. They were further analysed by in vitro characterisation studies that include erythrocyte aggregation study, electrolyte-induced study, heparin compatibility study and serum stability studies. SHSY5Y cells were used for conducting cytotoxicity of synthesised lipids and live imaging of cell uptake for 25 min. Finally, the brain distribution studies and western blot were carried out in animals to evaluate them for their BBB permeation ability and effects on p11 protein which is believed to be a culprit. These formulated liposomes from synthesised lipids offer a promising approach for the treatment of depression.