Microfluidics-assisted Aprotinin-based nano-carrier for Valproic acid delivery.

Area of Science:

• Nanomedicine
• Biomaterials Science
• Drug Delivery Systems

Background:

• Precision chemotherapy requires advanced drug delivery systems.
• Bio-derived nano-carriers offer a promising approach for targeted cancer treatment.
• Valproic Acid (VPA) is a histone deacetylase inhibitor with demonstrated anticancer properties.

Purpose of the Study:

• To develop and characterize a microfluidics-assisted nanoconjugate platform using Aprotinin (Apr) as a nano-carrier for Valproic Acid (VPA).
• To evaluate the in vitro and in vivo therapeutic potential and drug delivery enhancement of the Aprotinin-Valproic Acid (Apr-VPA) nanoconjugates.

Main Methods:

• Synthesis of Aprotinin-Valproic Acid (Apr-VPA) nanoconjugates using a flow-controlled microfluidic process.
• Physicochemical characterization of nanoconjugates.
• In vitro studies using 2D cell cultures and 3D tumor spheroid models.
• In vivo pharmacokinetic studies in mice using LC-MS/MS analysis.

Main Results:

• Stable Aprotinin-Valproic Acid (Apr-VPA) nanoconjugates were successfully synthesized.
• Apr-VPA nanoconjugates demonstrated dose-dependent inhibition of tumor spheroid growth and viability.
• Preliminary studies suggested selective cytotoxicity towards cancer cells over healthy endothelial cells.
• pH-responsive drug release was observed under acidic conditions.
• In vivo studies showed significantly enhanced plasma availability of VPA when conjugated.

Conclusions:

• Aprotinin is a feasible and scalable protein-based nanocarrier for enhancing VPA's therapeutic efficacy.
• The Aprotinin-Valproic Acid (Apr-VPA) nanoconjugate platform shows potential for tumor-preferential drug delivery and advanced nanomedicine applications.
• Further in vivo validation is warranted for potential clinical translation.