Biolistic delivery of liposomes protected in metal-organic frameworks

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 fragile biomaterials incapable of withstanding shear stress and are exceedingly difficult to formulate as a lyophilized powder for room temperature storage. Here we have developed a approach to deliver liposomes into the skin biolistically—by encapsulating them in a nano-sized shell made of Zeolitic Imidazolate Framework-8 (ZIF-8). When encapsulated within a crystalline and rigid coating, the liposomes are not only protected from thermal stress, but also shear stress. This protection from stressors is crucial, especially for formulations with cargo encapsulated inside the lumen of the liposomes. Moreover, the coating provides the liposomes with a solid exterior that allows the particles to penetrate the skin effectively. In this work, we explored the mechanical protection ZIF-8 provides to liposomes as a preliminary investigation for using biolistic delivery as an alternative to syringe-and-needle–based delivery of vaccines. We demonstrated that liposomes with a variety of surface charges could be coated with ZIF-8 using the right conditions, and this coating can be just as easily removed—without causing any damage to the protected material. The protective coating prevented the liposomes from leaking cargo and helped in their effective penetration when delivered into the agarose tissue model and porcine skin tissue.

In vivo biocompatibility of ZIF-8 for slow release via intranasal administration

“…Liposomes were synthesized and encapsulated in ZIF-8 using a previously published protocol (encapsulation with 20 mM zinc acetate and 640 mM 2-methylimidazole). 26 Cell culture, cytotoxicity measurement, and IC 50 determination A549, LLC-1, and OE33 cells were cultured in DMEM supplemented with FB essence, L-glutamine, and penicillinstreptomycin in T75 asks. All cells were grown at 37 °C, 5% CO 2 till 80% conuence.…”

“…12,13 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. 14,15 ZIF's versatility in capturing, preserving, and releasing antigens is exceptional and has been used to encapsulate whole viruses, 16,17 bacteria, 18 proteins, 19,20 DNA, 21,22 RNA, 23 yeast, 24 liposomes, 25,26 enzymes, 27,28 glycans, 29 and carbohydrates. 30 We have recently shown that ZIF-encapsulated formulations exhibit a depot effect, which signicantly enhances the efficacy of vaccine models.…”

The Promise and Potential of Metal–Organic Frameworks and Covalent Organic Frameworks in Vaccine Nanotechnology

“…34,35 Finally, most immunotherapeutic drugs require multiple doses through needle and syringe, requiring technical skills that cannot be quickly transferred to the general population or volunteers. 36 Disposable needles result in biohazardous waste, and their accidental (or intentional) reuse spreads bloodborne pathogens worldwide. 37 While intramuscular injections are more straightforward than intravenous injections, they are prone to neurovascular injuries.…”

Transformation of a copper-based metal–organic polyhedron into a mixed linker MOF for CO2 capture

“…Metal–organic frameworks (MOFs) are crystalline materials formed through the coordination of organic linkers to metal nodes. 1 MOFs are used in a variety of applications such as biomedicine, 2–6 catalysis, 7,8 sensors, 9–11 conductors, 12–15 gas storage and separations. 16–20 The capture and storage of CO 2 is a growing area of research.…”