Biolistic Delivery of MOF-Protected Liposomes

Abstract

Needle-and-syringe-based delivery has been the commercial standard for vaccine administration to date. With worsening medical personnel availability, increasing biohazard waste production, and the possibility of cross-contamination, we explore the possibility of biolistic delivery as an alternate skin-based delivery route. Delicate formulations like liposomes are inherently unsuitable for this delivery model as they are delicate biomaterials incapable of withstanding shear stress. When encapsulated within a crystalline and rigid coating made of zeolitic imidazolate frameworks, the liposomes are not only protected from thermal stress but also shear stress. The protection from shear stress is crucial, especially for formulations with cargo encapsulated inside the lumen of the liposomes. Moreover, the coating provides the liposomes a solid, rigid exterior which allows the particles to penetrate the tissue model and porcine tissue effectively.

In VivoBiocompatibility of ZIF-8 for Slow Release via Intranasal Administration

“…Liposomes were synthesized and encapsulated in ZIF using a previously published protocol (encapsulation with 20 mM zinc acetate and 640 mM 2-methylimidazole). [25]…”

“…[11, 12] ZIFs are unique as polymeric materials due to their kinetic lability; phosphate and carbonate salts, or albumin-rich environments readily pull the zinc from the framework causing it to dissolve completely, returning the original antigen to its pristine state. [13, 14] ZIF’s versatility in capturing, preserving, and releasing antigens is exceptional and has been used to encapsulate whole viruses,[15, 16] bacteria,[17] proteins,[18, 19] DNA,[20, 21] RNA,[22] yeast,[23] liposomes,[24, 25] enzymes,[26, 27] glycans,[28] and carbohydrates. [29] We have recently shown that ZIF-encapsulated formulations exhibit a depot effect, which significantly enhances the efficacy of vaccine models.…”