Prolonged Release Period of Nitric Oxide Gas for Treatment of Bacterial Keratitis by Amine-Rich Polymer Decoration of Nanoparticles

Abstract

Exogeneous nitric oxide (NO) delivery is a promising therapeutic method because NO is a significant cell signaling molecule to control physiological functions. A major challenge for NO delivery is to control release due to the fast diffusion properties of gaseous molecules with low molecular weight. It is important in biomedical applications to mitigate initial burst emissions because higher concentrations of reactive NO cause cytotoxicity and tissue damage. In this study, a nanoparticle system is developed to control spontaneous gas release on the basis of surface-modified silica nanoparticles (Si NPs) by branched polyethylene imine (BPEI). BPEI is not only a scaffold of N-diazeniumdiolatesa type of NO donorand but also a stabilizer of donors by molecular interactions with nearby amine groups. With the sustained-release manner, BPEI-coated NO-releasing Si NPs (BPEI-NO NPs) have multifunctional properties, including bactericidal efficacies as well as good cell viability for human cells. An improved ocular wound recovery is achieved in the mouse keratitis model. This study demonstrates the great potential of the NO-releasing NP as a multifunctional nanotherapeutic in biomedical applications.

Polymeric Nitric Oxide Delivery Nanoplatforms for Treating Cancer, Cardiovascular Diseases, and Infection

“…Although they have yielded excellent results, these approaches have the limitations of complicated production, less‐biocompatible reagent use, and initial rapid release of NO. [ 161 ]…”

Nitric Oxide (NO)-Releasing Macromolecules: Rational Design and Biomedical Applications

“…As a result, hybrid nanomaterials could be achieved by taking advantages of the physiochemical properties of inorganic nanoparticles and the therapeutic effect of NO (Yu et al, 2018). In this context, silica nanoparticles were coated with PEI and then treated the surface-bound PEI with NO with the formation of NONOate residues (Jeong et al, 2018). These hybrid nanoparticles displayed sustained and prolonged NO release behavior that can be used to treat bacterial keratitis.…”

Efficient Drug Delivery Carrier Surface without Unwanted Adsorption Using Sulfobetaine Zwitterion

“…Nano‐sized particles are currently being applied in various fields, such as drug delivery systems and coating materials because of their advantages, including large surface area, drug loading capacity, and versatility of chemical modification. [ 1–4 ] However, nanoparticles (NP) also have serious disadvantages, such as low colloidal stability and rapid clearance by the immune recognition system. [ 5,6 ] Among these, low colloidal stability (particle aggregation) can be fatal to the function of particles, such as drug release and targeting, which are closely related to the immune recognition system (fast cellular uptake because of increased size by aggregation and nonspecific absorption).…”