Nanogels as Pharmaceutical Carriers: Finite Networks of Infinite Capabilities

Abstract

Nanogels are swollen nano-sized networks composed of hydrophilic or amphiphilic polymer chains, which can be non-ionic or ionic. They are developed as carriers for drug delivery and can be designed to spontaneously absorb biologically active molecules through formation of salt bonds, hydrogen bonds, or hydrophobic interactions. Polyelectrolyte nanogels can readily incorporate oppositely charged low molecular mass drugs or biomacromolecules such as oligonucleotides, siRNA, DNA and proteins, which bind with the nanogel ionic chains and phase separate within the finite nanogel volume. As a result, the loading capacity of such nanogels is superior to most other drug carriers. Binding of the drugs induces collapse of nanogel, which usually decreases the volume by at least one order of magnitude. However, the drug-nanogel particles remain dispersed due to the lyophilizing effect of nanogel's hydrophilic polymer chains, such as poly(ethylene glycol) exposed at the particle surface. Multiple chemical functionalities of nanogels can be employed for introduction of imaging labels, targeting molecules and triggered drug release capabilities such as stimuli-responsive and degradable cross-links. Recent studies suggested several promising biomedical applications of nanogels, including drug delivery of phosphorylated nucleoside analogs, oligonucleotides or siRNA for anticancer or antiviral treatment, encapsulation of bioactive proteins, fabrication of nanometallic or nanoceramic composites, imaging agents, oral and CNS drug delivery. The research of different functional nanogels as novel pharmaceutical carriers for diagnosis and therapy shows promise and is rapidly developing.

Treatment of glioma by cisplatin-loaded nanogels conjugated with monoclonal antibodies against Cx43 and BSAT1

“…These soft polymeric materials formed monodisperse spherical nanoparticles with a diameter of $120-140 nm and a negative zetapotential (À20 ± 5 mV). Nanogels can be loaded with chemotherapeutics and exhibit a high loading capacity (cisplatin, 30-35%; doxorubicin, 40-45%) (Kabanov & Vinogradov, 2009). Ionic strength and pH are important for efficient drug encapsulation into nanogels.…”

“…The undesirable side effects of drugs could be significantly reduced by encapsulation of them into liposomes (Chekhonin et al, 2012), micelles (Oberoi et al, 2012), polymeric nanoparticles (Wohlfart et al, 2011;Steiniger et al, 2004) and other nanoparticles (Peer et al, 2007). Nanogels -nanoscale hydrogels based on hydrophilic or amphiphilic polymeric network -are one of the promising nanocontainers for platinum-based drugs (Kabanov & Vinogradov, 2009;Nukolova et al, 2011a). They are characterized by high loading capacity, tunable internal volume and high stability.…”

Advances in the application of nanotechnology in the diagnosis and treatment of gastrointestinal tumors

“…Nano-size hydrogels (often called nanogels) are swollen nano-sized networks formed by non-covalent interactions or covalent cross-linking of polymer chains (68). Given that nanogels have the properties of large surface area-to-volume ratio, size tunability, controlled drug release profile, excellent drug loading capacity and responsiveness to environmental stimuli, they have attracted significant attention in medicine as imaging labels and targeted drug delivery, while reducing systemic side effects (69).…”

Biocompatibility and characterization of polyglycerol-based thermoresponsive nanogels designed as novel drug-delivery systems and their intracellular localization in keratinocytes

“…Dendrimers composed of dendritic polyglycerol (dPG) are hyperbranched synthetic macromolecules that exhibit high-water solubility and biocompatibility (Goyal et al, 2016;Witting et al, 2015;Yang et al, 2012). Interestingly, dPG can serve as a macromolecular reagent to fabricate cross-linked hydrophilic three-dimensional polymeric networks referred to as nanogels (Asadian-Birjand et al, 2012aKabanov & Vinogradov, 2009). Moreover, dPG-based nanogels that respond to external stimuli such as temperature may enable targeted and controlled drug transport (Bergueiro & Calderon, 2015;Cuggino et al, 2011a).…”