Liposome Consolidated with Cyclodextrin Provides Prolonged Drug Retention Resulting in Increased Drug Bioavailability...

Area of Science:

• Pharmaceutical Sciences
• Nanotechnology
• Oncology

Background:

• Butylidenephthalide (BP) is an effective anticancer agent but suffers from poor bioavailability, hindering its efficacy against drug-resistant brain tumors.
• Intranasal drug delivery offers a noninvasive route to bypass the blood-brain barrier and improve drug bioavailability for brain tumor treatment.

Purpose of the Study:

• To develop and characterize a novel drug delivery system for butylidenephthalide (BP) using cyclodextrin-encapsulated BP in liposomal formulations (CDD1).
• To evaluate the enhanced bioavailability, stability, and efficacy of the CDD1 system for treating temozolomide-resistant glioblastoma multiforme in preclinical models.

Main Methods:

• Formulation of cyclodextrin-encapsulated BP in liposomes (CDD1) and characterization using dynamic light scattering, transmission electron microscopy, UV-Vis spectroscopy, and NMR spectroscopy.
• In vitro assessment of cytotoxicity via MTT assay and cellular uptake via fluorescence microscopy.
• In vivo evaluation in nude mice with intracranial glioblastoma xenografts, assessing median survival time and drug biodistribution using liquid chromatography-mass spectrometry.

Main Results:

• The CDD1 system demonstrated high encapsulation efficiency (up to 95%) and improved BP stability and bioavailability.
• CDD1 showed enhanced cellular retention (>8 h) and significant cytotoxicity against drug-resistant glioblastoma cells.
• Intranasal administration of CDD1 in mice significantly increased median survival time and led to a 10-fold higher brain accumulation of BP compared to oral delivery.

Conclusions:

• Cyclodextrin-encapsulated BP in liposomal formulations (CDD1) represents a promising strategy to overcome the bioavailability limitations of BP.
• Intranasal delivery of CDD1 offers a viable noninvasive approach for enhanced drug delivery to the brain, showing significant therapeutic potential for drug-resistant brain tumors.