Development of Lomustine and n-Propyl Gallate Co-Encapsulated Liposomes for Targeting Glioblastoma Multiforme via Intranasal Administration

Abstract

This work aimed to develop lomustine (LOM) and n-propyl gallate (PG)-loaded liposomes suitable for targeting glioblastoma multiforme (GBM) via the auspicious nose-to-brain drug delivery pathway. The therapeutical effect of LOM, as a nitrosourea compound, can be potentiated by PG suitable for enhanced anti-cancer therapy. Nose-to-brain delivery of PG and LOM combined in liposomes can overcome the poor water solubility, absorption properties, and toxicity issues in the systemic circulation. Optimization and characterization of the liposomal carrier with binary drug contents were carried out in order to achieve adequate encapsulation efficiency, loading capacity, drug release, and ex vivo permeation. The optimized liposome co-encapsulated with both drugs showed suitable Z-average (127 ± 6.9 nm), size distribution (polydispersity index of 0.142 ± 0.009), zeta potential (−34 ± 1.7 mV), and high encapsulation efficacy (63.57 ± 1.3% of PG and 73.45 ± 2.2% of LOM, respectively) meeting the acceptance criteria of nose-to-brain transport for both drugs. MTT assays of PG-LOM formulations were also conducted on NIH/3T3 (murine embryonic fibroblast), U87 (glioblastoma), and A2780 (ovarian cancer) cell lines indicating reduced an antiproliferative effect on all types of cells. Our results supported the use of this novel combination of LOM and PG in a liposomal formulation as a promising carrier for glioblastoma targeting via the intranasal route.

Perspective Chapter: Nose-to-Brain Drug Delivery through Liposomes - Recent Applications

“…MTT assays of the developed formulation were also performed on murine embryonic fibroblast (NIH/3T3), glioblastoma (U87), and ovarian (A2780) cancer cell lines. The results of in vitro cancer cell line indicated a reduction in cancerous cells of all studied types [42].…”

Glioblastoma Treatment: State-of-the-Art and Future Perspectives

“…The production of O6 -chloroethylguanine, which can be reversed by MGMT, is one of the most important lesions generated by lomustine [38]. By carboxylation of amino acids, such as lysine or arginine, lomustine may impede enzymatic processes, leading to cell death through TRC8-mediated degradation targeting heme oxygenase-1 [39]. However, the clinical relevance of this action is uncertain.…”

Temozolomide Efficacy and Metabolism: The Implicit Relevance of Nanoscale Delivery Systems

“…Liposomal targeted therapy with temozolomide demonstrated a significant increase in survival in mice, demonstrating a life expectancy increase by 62%. This approach makes it possible to reduce the dose of the drug and suppress the development of drug resistance [ 54 , 55 , 56 , 57 , 58 , 59 ].…”

“…Despite the increased effectiveness in comparison with traditional methods of drug delivery, and the promising properties of liposomes, there is still no FDA-approved clinical liposomal product for the treatment of CNS pathologies. This is due to spontaneous factors that cannot be embraced by studies [ 51 , 56 , 57 ].…”