Polybasic Nanomatrices Prepared by UV-Initiated Photopolymerization

Abstract

A novel method for synthesizing nanoscale polymer networks that swell in acidic media is described here using photoinitiated emulsion polymerization. These nanomatrices consist of a crosslinked core of poly[2-(diethylamino)ethyl methacrylate] surface grafted with poly(ethylene glycol) (PDGP) with an average diameter of 50-150 nm. Control over mesh size, surface charge, encapsulation efficiency and in vitro biocompatibility was obtained by varying crosslinking density. The ability to image nanomatrices in their dry state using conventional scanning electron microscopy was made possible by increasing crosslinking density. Theoretical calculations of matrix mesh sizes were supported by the encapsulation of both insulin and colloidal gold 2-5 nm in diameter. The ability to sequester and control the aggregation of an inorganic phase confirmed their use as a nanocomposite matrix material. These networks could be used as imaging agents, drug delivery devices or as components of sensing devices.

One-pot synthesis of pH-responsive hybrid nanogel particles for the intracellular delivery of small interfering RNA

“…These results are in agreement with those reported by Peppas and colleagues [26, 43], who demonstrated that PDEAEM has a pKa of about 7.2. Therefore the buffering properties of this polymer can exploit the endosomal acidic environment (pH < 7.2).…”

“…As demonstrated by the group of Peppas [26, 43], PDEAEM has a pKa of ~7.2, therefore, its buffering properties can exploit the endosomal acidic environment (pH < 7.2). Thanks to this phenomenon, CXCR4 siRNA was efficiently delivered into the cytoplasm of MDA-MB-231 breast cancer cells and inhibited the protein expression of CXCR4 with an efficacy comparable to that of a commercial transfection reagent [58, 59].…”

Advanced molecular design of biopolymers for transmucosal and intracellular delivery of chemotherapeutic agents and biological therapeutics

“…Nanoscale hydrogels were synthesized via UV-initiated free radical photoemulsion polymerization according to previous reports from our laboratory [3, 37]. Briefly, 2-(diethylamino) ethyl methacrylate (DEAEMA, Sigma-Aldrich), 2-( tert- butylamino)ethyl methacrylate ( t -BAEMA, Polysciences, Inc.), tert- butylamino methacrylate ( t -BMA, Sigma-Aldrich), and tetra(ethylene glycol) dimethacrylate (TEGDMA, Sigma-Aldrich) were passed through a column of basic alumina powder to remove inhibitor prior to use.…”

“…Several recent efforts have explored the utility of responsive nanoscale hydrogel carriers in drug delivery [3, 37–39], demonstrating release of biological therapeutics such as insulin and imaging agents such as gold. Nanoscale hydrogels are increasingly attractive as drug delivery agents owing to their facile manufacture, tunable physicochemical characteristics, and repeatable release.…”

“…Amine-containing methacrylates, such as 2-(diethylaminoethyl) methacrylate (DEAMA) [59] and 2-(dimethylaminoethyl) methacrylate (DMAEMA) [60], are attractive foundations for polymeric nucleic acid-delivery systems because of their ability to form cooperative electrostatic interactions with polyanionic siRNA. We have previously developed DEAEMA-based polycationic nanogels [3, 37] and are currently investigating their utility as highly-efficient siRNA delivery vectors. However, a critical aspect of intracellular delivery systems is a mechanism for elimination or degradation.…”