Student Theses, Dissertations and Capstones

Document Type

Dissertation - NSU Access Only

Degree Name

Doctor of Philosophy (PhD) in Pharmacy

First Advisor

Young M. Kwon

Defense Date

1-1-2024

Abstract

Despite diverse treatment options, brain cancers remain fatal, causing significant annual mortality in the United States. The challenges in effectively targeting and delivering chemotherapeutic agents to brain tumors limit the success of chemotherapy. This study explores niosomal nanovesicles to enhance the delivery of Temozolomide (TMZ), a lipophilic anticancer drug, aiming to improve glioblastoma treatment outcomes. Using the thin film hydration method, this research optimizes the formulation parameters of niosomal nanovesicles. The study demonstrates that the molar ratios of the nonionic surfactant Span 60, and cholesterol significantly influence TMZ's encapsulation efficiency and release profile. The optimal formulation achieved around 73% entrapment efficiency with sustained release of about 70% over 24 hours, attributable to favorable hydrophobic interactions and optimal membrane incorporation. Comparative stability studies showed that niosomes exhibited superior physical and biochemical stability compared to liposomes. Niosomes maintained stability under various conditions, with minimal aggregation over extended storage periods. Conversely, liposomes displayed rapid aggregation and significant changes in vesicle size and zeta potential. Biochemically, niosomes facilitated a slower, controlled release of TMZ in the presence of PLA2 enzyme, compared to the rapid enzymatic degradation observed in liposomes. Cytotoxicity assessments confirmed that blank niosomes were non-toxic to HBEC-5i cells, whereas both free TMZ and TMZ-loaded niosomes were cytotoxic to U-87 MG cells. Notably, TMZ-loaded niosomes exhibited greater cytotoxicity than free TMZ, likely due to enhanced cellular uptake facilitated by niosome encapsulation. In conclusion, this research underscores the potential of niosomal nanovesicles to enhance TMZ delivery, providing improved stability and therapeutic efficacy. These findings suggest that niosomal systems could play a significant role in targeted cancer therapy, particularly for glioblastoma, by optimizing drug delivery and minimizing side effects. Future research should focus on in vivo studies to validate these formulations' clinical relevance and explore their applicability to other chemotherapeutic agents.

Subject Categories

Pharmacy and Pharmaceutical Sciences

Keywords

Enzymatic Stability; Glioblastoma; Liposome; Niosome; Phospholipase A2; Temozolomide

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