One-step solid-oil-water emulsion for sustained bioactive ranibizumab release

ABSTRACT

Background: The advent of therapeutic proteins highlights the need for delivery systems that protect and extend the duration of its action. Ranibizumab-VEGF is one such drug used for treating wet AMD. This paper describes a facile method to sustain bioactive ranibizumab release from PLGA-based particles.

Methods: Two emulsion techniques were explored namely: water-in-oil-in-water (WOW) and solid-in-oil-in-water (SOW) emulsion. The bioactivity of ranibizumab was evaluated by comparing its binding capability to VEGF, measured with ELISA to total protein measured by microBCA.

Results: During the emulsion process, contact of ranibizumab with the water-oil interface is the main destabilizing factor and this can be prevented with the use of amphiphilic PVA and solid-state protein in WOW and SOW emulsion respectively. In vitro release of the ranibizumab-loaded particles indicated that a 15-day release could be achieved with SOW particles while the WOW particles generally suffered from a burst release. Released ranibizumab was capable of inhibiting endothelial cell growth indicating its retention of bioactivity. The suppression of burst release from the SOW particles was attributed to the relatively smooth surface morphology of the SOW microparticles.

Conclusions: The use of SOW encapsulation in modulating ranibizumab release while maintaining their bioactivity has been highlighted.

KEYWORDS:

• Bioactive
• PLGA
• ranibizumab
• solvent emulsion-evaporation
• sustained release

Acknowledgments

The authors will like to acknowledge Fan Yan Liang for her help in Confocal Raman Spectroscopy and Tabitha Tan Su Teng for her help in Gel Electrophoresis.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Conception and design: HY Chua, YS Lui, R Bhuthalingam, S Venkatraman, PR Preiser. Analysis and Interpretation of data: HY Chua, YS Lui, R Bhuthalingam, T Wong, R Agrawal. Drafting the paper/revising it critically: HY Chua, R Bhuthalingam, S Venkatraman, PR Preiser. Final approval of the version to be published: HY Chua, YS Lui, R Bhuthalingam, S Venkatraman, PR Preiser, T Wong, R Agrawal. All authors agree to be accountable for all aspects of the work.

Additional information

Funding

The authors were supported by Nanyang Technological University-Northwestern Institute for Nanomedicine grant M4081501.F40 and Ministry of Education, Singapore Scholarship.