Speaker
Abstract
Abstract
Background: Lomustine is an effective alkylating agent used for both primary and metastatic brain tumors, but its clinical effectiveness is impeded by poor aqueous solubility and high lipophilicity. Therefore, solusomes are novel nanovesicles combining the amphiphilic copolymer Soluplus® with different phosphatidylcholine. Which offer a specialized nanocarrier to improve the delivery and bioavailability of lomustine to the brain.
Objective: This study estimates the role of different phosphatidylcholine types (egg yolk and soya lecithin) in the preparation and evaluation of lomustine-loaded solusomes to detect the optimum composition for enhanced drug chemotherapy.
Method: Using the thin-film hydration technique with different ratios of phosphatidylcholine, Soluplus®, and cholesterol to prepare fourteen solusome formulations (F1 to F14). Furthermore, evaluations to obtain optimal size, polydispersity index, zeta potential, and entrapment efficiency. Therefore, selected formulations were submitted to in vitro release and ex vivo permeation studies.
Results: F10 (soya lecithin-based) led to a smaller size (93.85 nm), higher entrapment efficiency (98.25%), greater nanovesicle stability with a higher zeta potential (-31.22 mV), and in vitro release reached 83% cumulative amount in 120 minutes. While permeation parameters included flux, it was approximately five-fold higher than the lomustine suspension due to the presence of the lipid mixture. Also, it's enhanced the elasticity due to the presence of amphiphilic copolymer. So, soya lecithin-based formulations constantly performed better than egg yolk-based formulations. Finally, stability studies confirmed the lomustine-loaded nanovesicles remained stable for one month under refrigeration due to the presence of cholesterol.
Conclusion: the research found a superior solusome nanocarrier, indicating that soya lecithin combined with Soluplus® significantly improves lomustine solubility, stability, permeation, and bioavailability. Finally, this system offers a promising approach for innovative brain targeting and enhancing chemotherapeutic effect in treating brain tumors.
