The
increasing rate of resistance of bacterial infection against
antibiotics requires next generation approaches to fight potential
pandemic spread. The development of vaccines against pathogenic bacteria
has been difficult owing, in part, to the genetic diversity of bacteria.
Hence, there are many potential target antigens and little a priori knowledge of which antigen/s will elicit protective
immunity. The painstaking process of selecting appropriate antigens
could be avoided with whole-cell bacteria; however, whole-cell formulations
typically fail to produce long-term and durable immune responses.
These complications are one reason why no vaccine against any type
of pathogenic E. coli has been successfully clinically
translated. As a proof of principle, we demonstrate a method to enhance
the immunogenicity of a model pathogenic E. coli strain
by forming a slow releasing depot. The E. coli strain
CFT073 was biomimetically mineralized within a metal–organic
framework (MOF). This process encapsulates the bacteria within 30
min in water and at ambient temperatures. Vaccination with this formulation
substantially enhances antibody production and results in significantly
enhanced survival in a mouse model of bacteremia compared to standard
inactivated formulations.
The efficacy and specificity of protein, DNA, and RNA-based drugs make them popular in the clinic; however, these drugs are often delivered via injection, requiring skilled medical personnel, and producing...
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.
Studying the toxicity of zeolitic imidazolate framework-8 (ZIF-8) in context of intranasal administration will help researchers in building depot platforms for this non-invasive route of delivery.
A novel
copper(II) metal–organic framework (MOF) has been
synthesized by modifying the reaction conditions of a 1D coordination
polymer. The 1D polymer is built by the coordination between copper
and 2,2′-(1H-imidazole-4,5-diyl)di-1,4,5,6-tetrahydropyrimidine
(H-L1). The geometry of H-L1 precludes its ability to form extended
3D framework structures. By adding 1,4-benzenedicarboxylic acid (H2BDC), a well-studied linker in MOF synthesis, we achieved
the transition from a 1D polymer chain into porous 2D layered structures.
Hydrogen bonding between L1 and BDC directs the parallel stacking
of these layers, resulting in a 3D structure with one-dimensional
channels accessible by two different pore windows. The preferred growth
orientation of the crystal produces prolonged channels and a disparity
in pore size distribution. This in turn results in slow diffusion
processes in the material. Furthermore, an isoreticular MOF was prepared
by substituting the BDC linker by 2,6-naphthalenedicarboxylic acid
(H2NDC).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.