Nopal mucilage-encapsulated poly (butylene adipate-co-terephthalate) nanoparticles for efficient gallic acid delivery in glioblastoma cells


ÇAKIR D., GÜMÜŞDERELİOĞLU M.

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, cilt.110, 2025 (SCI-Expanded, Scopus) identifier

Özet

Glioblastoma Multiforme (GBM) is the most common and difficult-to-treat brain tumor. Standard treatment includes surgical resection, when feasible, followed by radiotherapy and chemotherapy. However, its efficacy is limited by issues like poor drug delivery to the tumor and high drug toxicity. In the present study, site-specific controlled nanoparticulate drug delivery approach complementary to standard treatment methods was developed using natural agents, gallic acid (GA) and Opuntia ficus indica (nopal) mucilage (ONM). GA-loaded poly (butylene adipate-co-terephthalate) (PBAT) nanoparticles (GA-PBAT NPs) were produced using a modified double emulsion preparation-solvent evaporation method. The impact of parameters on particle size and encapsulation efficiency of GA was investigated by Response Surface Methodology (RSM) and the GA/PBAT ratio (w/w) was identified as the most effective parameter on system responses. GA-PBAT NPs were produced according to the optimized parameters, with a particle size and encapsulation efficiency of 190 +/- 69 nm and 87.2 +/- 6.9 %, respectively. GA-PBAT NPs were coated with ONM to obtain GA-ONM-PBAT NPs. At the end of 7 days, 57 % of GA was released from GA-ONM-PBAT NPs in a more controlled manner compared to GA-PBAT NPs. The IC50 value for GA was calculated as similar to 750 mu M after 5 days on T98G human glioblastoma cells. ONM coating induced apoptosis, increasing the anticancer effect of GA, along with some necrotic death. GA-ONM-PBAT nanoparticles promoted therapeutic efficacy through multiple signaling pathways. They suppressed the expression of c-Myc and beta-catenin genes in T98G glioblastoma cells while promoting caspase-3 expression. Consequently, GA-ONM-PBAT NPs have the potential to be used in advanced research for GBM therapy, presenting an innovative nanoparticulate drug delivery system.