Receptor-mediated nose-to-brain delivery of drug combination-loaded polymeric nanocarriers for the treatment of glioblastoma- current progress and future perspectives part II: polymeric nanocarriers for combination therapy and advanced targeting.

Introduction: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a bleak prognosis, complicated by factors such as the blood-brain barrier (BBB), the tumor's heterogeneity, and the systemic toxicity associated with standard therapies. Utilizing receptor-mediated delivery through nasal routes with polymeric nanocarriers provides a noninvasive approach to enhance brain targeting, improve therapeutic outcomes, and increase safety.

Area covered: This review focuses on polymeric nanocarriers, including nanoparticles, nanocapsules, dendrimers, and micelles, for use in combination therapy for GBM. It emphasizes targeting overexpressed receptors, advanced carrier designs that enable controlled or responsive release, and multifunctional systems with theranostic capabilities. Additionally, it highlights immunomodulatory and personalized strategies, underscoring their importance for clinical translation.

Expert opinion: Polymeric nanocarriers designed for receptor-mediated delivery from the nose to the brain offer a revolutionary approach for combination therapy in GBM, enhancing drug absorption, specificity, and therapeutic effectiveness. Although promising advancements have been made in preclinical studies, their translation to clinical settings is hindered by physiological barriers in the nose, complex formulations, and challenges related to scalability. Moving forward will necessitate refined nanocarrier design, accurate receptor targeting, and thorough clinical testing to confirm these systems as advanced treatment platforms for GBM.