Pickering emulsions with ethiodized oil and nanoparticles for slow release of intratumoral anti-CTLA4 immune checkpoint antibodies

Intratumorous immunotherapy for cancer is currently thriving. The

Pickering emulsions of ethiodized oil and PLGA is an innovative radiopaque delivery platform that does not alter the functionality of anti-CTLA4 immune checkpoint antibodies. Beyond local anti-CTLA4 applications, these emulsions might be used with other therapeutic molecules for optimal intratumorous or intra-arterial delivery of novel cancer immunotherapies.

Pickering emulsions of anti-CTLA4 antibodies were formulated with radiopaque ethiodized oil and poly-lactic-co-glycolic acid (PLGA) nanoparticles. We characterized the microscopic aspect and stability of such emulsions using Turbiscan. We monitored the release of anti-CTLA4 over time from these emulsions and evaluated their structure using mass spectrometry. We then tested the functionality of the released antibodies by preforming ex vivo competitive binding assays. Finally, we assessed the in vivo efficacy of intratumorous anti-CTLA4 Pickering emulsions.

Pickering emulsions of ethiodized oil and PLGA nanoparticles (PEEPs) resulted in a radiopaque water-in-oil emulsion with average internal phase droplet size of 42±5 µm at day 7. Confocal microscopy showed that anti-CTLA4 antibodies were effectively encapsulated by ethiodized oil with PLGA nanoparticles located at the interface between the aqueous and the oily phase. Turbiscan analysis showed that emulsions were stable with continuous and progressive release of anti-CTLA4 antibodies reaching 70% at 3 weeks. Structural and functional analysis of the released antibodies did not show significant differences with native anti-CTLA4 antibodies. Finally, intratumorous anti-CTLA4 PEEPs were able to eradicate tumors and cure mice in a syngeneic immunocompetent preclinical tumor model.