Polyamide Nanogels from Generally Recognized as Safe Components and Their Toxicity in Mouse Preimplantation Embryos

Abstract

Safe delivery systems that can not only encapsulate hydrophobic drug molecules, but also release them in response to specific triggers, are important in several therapeutic and biomedical applications. In this paper, we have designed a nanogel based on molecules that are generally recognized as safe (GRAS). We have shown that the resultant polymeric nanogels exhibit responsive molecular release, and also show high in vitro cellular viability on HEK 293T, HeLa, MCF 7 and A549 cell lines. The toxicity of these nanogels was further evaluated with a highly sensitive assay using mouse preimplantation embryo development, where blastocysts were formed after four days of in vitro culture and live pups were born when morulae/early blastocysts were transferred to the uteri of surrogate recipients. Our results indicate that these nanogels are non-toxic during mammalian development and do not alter normal growth or early embryo success rate.

Bait-and-Switch Supramolecular Strategy To Generate Noncationic RNA–Polymer Complexes for RNA Delivery

“…Next, to evaluate the RNAi efficiency and toxicity of our system, we employed the mouse preimplantation embryo model. It has been well established that mammalian embryo development is more sensitive to perturbations than in vitro cultured cell lines. , Previous study has introduced a noncationic lipid gene delivery system into chicken embryos via microinjection . In our study, we chose to target Tuba1a and evaluate if culturing with our RNA–polymer complex can result in blastocyst failure phenotype .…”

Biodegradable Smart Nanogels: A New Platform for Targeting Drug Delivery and Biomedical Diagnostics

“…This disulfide cross-linked polymeric nanogels was composed of molecules that could be used as food additives or as medical devices. Neither the in vitro tissue culture cytotoxicity assay nor a more rigorous and highly sensitive mammalian preimplantation development assay of the nanogels exhibited discernible toxicity …”

“…Neither the in vitro tissue culture cytotoxicity assay nor a more rigorous and highly sensitive mammalian preimplantation development assay of the nanogels exhibited discernible toxicity. 22 Various inorganic and organic small molecules containing Se are widely studied as anticancer drugs with high antitumor activities. In addition, the Se−Se bond is stimuli-responsive to both reductive and oxidative conditions, owing to the low bond energy (Se−Se 172 kJ mol −1 ).…”

Amphiphilic micro‐ and nanogels: Combining properties from internal hydrogel networks, solid particles, and micellar aggregates

“…Thus, these systems are a perfect example of combining the excellent biocompatibility of the designed hydrogel networks with the ability to load and release hydrophobic compounds. 108 In summary, these examples demonstrate that crosslinked random copolymer micelles enable the random distribution of hydrophobic and hydrophilic moieties in the polymer networks. In combination with the high-colloidal stability, enhanced loading capacity for hydrophobic compounds, and good biocompatibility, they represent interesting new microÀ/nanogels for various applications.…”

“…In a following study, they used the disulfide exchange crosslinking for the development of nanogels from components that are generally recognized as safe (GRAS). 108 For this, glutamic acid and putrescine were chosen as monomers to prepare degradable polyamide backbones with functionalized hydrophilic oligoethylene glycol moieties and hydrophobic 2-(pyridyldisulfide) (PDS) moieties. These polymers self-assembled in water and the resulting micelles were crosslinked by the addition of GSH to form disulfide crosslinking points.…”