Sustained Ocular Delivery of Bevacizumab Using Densomeres in Rabbits: Effects on Molecular Integrity and Bioactivity

Area of Science:

• Ophthalmology
• Biomaterials Science
• Drug Delivery

Background:

• Anti-angiogenic therapies are crucial for treating neovascular eye diseases.
• Delivering biologics like monoclonal antibodies requires advanced drug delivery systems for sustained efficacy.
• Bevacizumab is a potent anti-angiogenic antibody often used off-label in ophthalmology.

Purpose of the Study:

• To evaluate a novel biodegradable Densomere carrier for sustained delivery of bevacizumab.
• To assess the molecular integrity, release kinetics, and bioactivity of bevacizumab from Densomere microparticle carriers (DMCs).
• To demonstrate prolonged in vitro and in vivo therapeutic effects for up to 12 months.

Main Methods:

• Bevacizumab was incorporated into Densomere microparticle carriers (DMCs) at 5% loading.
• In vitro release profiles were monitored over 12 months.
• Molecular integrity was assessed using ELISA and SEC-HPLC.
• In vivo anti-angiogenic efficacy was evaluated in a rabbit corneal suture model.

Main Results:

• Continuous in vitro release of bevacizumab from DMCs was observed for 12 months.
• Released bevacizumab maintained molecular integrity, confirmed by ELISA and SEC-HPLC.
• A single subconjunctival administration of bevacizumab-loaded DMCs significantly suppressed corneal neovascularization for 12 months in rabbits.

Conclusions:

• The Densomere carrier platform effectively preserves bevacizumab's molecular integrity and provides sustained release.
• This system demonstrates prolonged in vivo bioactivity, offering a promising approach for long-term ocular drug delivery.
• Densomere represents a significant advancement for prolonged delivery of biologics in ocular and other tissues.