Catechol Containing Polyelectrolyte Complex Nanoparticles as Local Drug Delivery System for Bortezomib at Bone...

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Nanotechnology

Background:

• The proteasome inhibitor bortezomib (BZM) is crucial for multiple myeloma therapy.
• Existing polyelectrolyte complex (PEC) nanoparticle (NP) drug delivery systems (DDS) rely on electrostatic interactions.
• There is a need for DDS that can effectively deliver uncharged drugs like BZM through covalent bonding.

Purpose of the Study:

• To develop an adhesive DDS for bortezomib (BZM) utilizing covalent bonding.
• To create a novel chemo-reactive polyanion, PDOPAC, for drug conjugation.
• To investigate the loading capacity and release characteristics of the developed DDS.

Main Methods:

• Polymerization of 3,4-dihydroxyphenyl acetic acid (DOPAC) to form PDOPAC.
• Formation of PEC NPs by admixing PDOPAC with poly(l-glutamic acid) (PLG) and poly(l-lysine) (PLL).
• Loading of BZM via esterification between PDOPAC's catechol groups and BZM's boronic acid groups.
• Drug release studies on bone substitute materials.

Main Results:

• The developed DDS involves covalent bonding between PDOPAC and BZM.
• Loading capacity (LC) is influenced by PDOPAC content, catechol content, loading type, and NP net charge.
• The DDS demonstrated effective BZM release from coatings on calcium phosphate cement and titanium niobium alloy.
• Covalently bound BZM release is independent of ionic strength, unlike electrostatic loading.

Conclusions:

• A novel DDS for uncharged bortezomib (BZM) was successfully developed using covalent bonding.
• The PDOPAC-based PEC NP system offers advantages for drug loading and processing.
• The DDS exhibits robust performance on various medical materials and stable release kinetics.