Characterization of the Biodistribution of a Silica Vesicle Nanovaccine Carrying a Rhipicephalus (Boophilus) microplus Protective Antigen With in vivo Live Animal Imaging

Development of veterinary subunit vaccines comes with a spectrum of challenges, such as the choice of adjuvant, antigen delivery vehicle, and optimization of dosing strategy. Over the years, our laboratory has largely focused on investigating silica vesicles (SVs) for developing effective veterinary vaccines for multiple targets. Rhipicephalus microplus (cattle tick) are known to have a high impact on cattle health and the livestock industry in the tropical and subtropical regions. Development of vaccine using Bm86 antigen against R. microplus has emerged as an attractive alternative to control ticks. In this study, we have investigated the biodistribution of SV in a live animal model, as well as further explored the SV ability for vaccine development. Rhodamine-labeled SV-140-C18 (Rho-SV-140-C18) vesicles were used to adsorb the Cy5-labeled R. microplus Bm86 antigen (Cy5-Bm86) to enable detection and characterization of the biodistribution of SV as well as antigen in vivo in a small animal model for up to 28 days using optical fluorescence imaging. We tracked the in vivo biodistribution of SVs and Bm86 antigen at different timepoints (days 3, 8, 13, and 28) in BALB/c mice. The biodistribution analysis by live imaging as well as by measuring the fluorescent intensity of harvested organs over the duration of the experiment (28 days) showed greater accumulation of SVs at the site of injection. The Bm86 antigen biodistribution was traced in lymph nodes, kidney, and liver, contributing to our understanding how this delivery platform successfully elicits antibody responses in the groups administered antigen in combination with SV. Selected tissues (skin, lymph nodes, spleen, kidney, liver, and lungs) were examined for any cellular abnormalities by histological analysis. No adverse effect or any other abnormalities were observed in the tissues

Direct comparison of poly(ethylene glycol) and phosphorylcholine drug-loaded nanoparticles in vitro and in vivo

Phosphorylcholine is known to repel the absorption of proteins onto surfaces, which can prevent the formation of a protein corona on the surface of nanoparticles. This can influence the fate of nanoparticles used for drug delivery. This material could therefore serve as an alternative to poly(ethylene glycol) (PEG). Herein, the synthesis of different particles prepared by polymerization-induced self-assembly (PISA) coated with either poly(ethylene glycol) (PEG) or zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) and 4-(-(-penicillaminylacetyl)amino) phenylarsenonous acid (PENAO) was reported. The anticancer drug 4-(-(-penicillaminylacetyl)amino) phenylarsenonous acid (PENAO) was conjugated to the shell-forming block. Interactions of the different coated nanoparticles, which present comparable sizes and size distributions (76-85 nm, PDI = 0.067-0.094), with two-dimensional (2D) and three-dimensional (3D) cultured cells were studied, and their cytotoxicities, cellular uptakes, spheroid penetration, and cell localization profiles were analyzed. While only a minimal difference in behaviour was observed for nanoparticles assessed using in vitro experiment (with PEG-- PENAO-coated micelles showing slightly higher cytotoxicity and better spheroid penetration and cell localization ability), the effect of the different physicochemical properties between nanoparticles had a more dramatic effect on in vivo biodistribution. After 1 h of injection, the majority of the MPC--PENAO-coated nanoparticles were found to accumulate in the liver, making this particle system unfeasible for future biological studies

Oral delivery of multicompartment nanomedicines for colorectal cancer therapeutics: combining loco-regional delivery with cell-target specificity

Nanomaterials for targeted delivery of chemotherapeutics have received significant attention owing to their potential to enhance the accumulation of therapeutics in diseased tissue. However, in diseases with poor vascularization, such as colorectal cancer (CRC), intravenously injected materials have reduced access to the site of interest. To overcome this challenge, oral administration of targeted nanomedicines is highly desirable. Here, a multicomponent drug delivery system incorporating a degradable alginate microcapsule, formulated to encapsulate micelles targeted to the CD44 receptor is presented. Functional micelles are generated by coupling hyaluronic acid (to target CD44 receptor) to block copolymers of poly(ethylene glycol) monomethyl ether methacrylate and poly(methyl methacrylate). When encapsulated into alginate microcapsules, these micelles form the basis of a novel oral delivery system that offers protection from degradative compartments of the gastrointestinal tract (GIT) and regio-specific release. The microcapsules demonstrate desirable site-specific degradation properties in an orthotopic CRC xenograft mouse model, yielding enhanced accumulation of micelles within CD44+ colorectal tumors. The results illustrate that such materials successfully navigate the GIT, regio-specifically release targeted micelles at the tumor site, and consequently accomplish enhanced accumulation within tumor tissue. Such multi-component nanomaterials offer a promising means for addressing challenges in treating CRC and difficult to treat diseases