The Potential of Stimuli-Responsive Nanogels in Drug and Active Molecule Delivery for Targeted Therapy

Abstract

Nanogels (NGs) are currently under extensive investigation due to their unique properties, such as small particle size, high encapsulation efficiency and protection of active agents from degradation, which make them ideal candidates as drug delivery systems (DDS). Stimuli-responsive NGs are cross-linked nanoparticles (NPs), composed of polymers, natural, synthetic, or a combination thereof that can swell by absorption (uptake) of large amounts of solvent, but not dissolve due to the constituent structure of the polymeric network. NGs can undergo change from a polymeric solution (swell form) to a hard particle (collapsed form) in response to (i) physical stimuli such as temperature, ionic strength, magnetic or electric fields; (ii) chemical stimuli such as pH, ions, specific molecules or (iii) biochemical stimuli such as enzymatic substrates or affinity ligands. The interest in NGs comes from their multi-stimuli nature involving reversible phase transitions in response to changes in the external media in a faster way than macroscopic gels or hydrogels due to their nanometric size. NGs have a porous structure able to encapsulate small molecules such as drugs and genes, then releasing them by changing their volume when external stimuli are applied.

Smart Nanoparticles for Drug Delivery Application: Development of Versatile Nanocarrier Platforms in Biotechnology and Nanomedicine

“…The properties of hydrogels can be tuned to match the needs of specific applications by the choice of a specific polymer (molecular structure and segments length), the crosslinking mechanism, and the eventual presence of acidic (or basic) polymer moieties, whose state of protonation can be easily controlled with pH or salt concentration. Stimulus-responsive (smart) hydrogels can undergo structural transitions in response to external stimuli or (internal) environment changes of the physical properties of the system such as its temperature, electric field, and exposure to light [49,50].…”

Advances in Stimuli‐Responsive Polypeptide Nanogels

“…Polymer nanogels, which are nanosized particles of hydrogels, integrate the characteristics of hydrogels and nanoparticles into one platform . In comparison to other polymer‐based drug nanocarriers, e.g., micelles, liposomes, and polymer–drug conjugates, nanogels have significant advantages .…”

“…Stimuli‐responsive polypeptide nanogels are one of these realized possibilities and they have led to a great revolution in drug delivery . Traditional polypeptide nanogels fail to meet the requirements of an appropriate drug delivery platform; more specifically, the drug molecules do not remain stable in the carrier during circulation until arriving at the target site . As a result, stimuli‐responsive polypeptide nanogels have been widely studied to achieve controllable drug release .…”

“…[34] Traditional polypeptide nanogels fail to meet the requirements of an appropriate drug delivery platform; more specifically, the drug molecules do not remain stable in the carrier during circulation until arriving at the target site. [1] As a result, stimuli-responsive polypeptide nanogels have been widely studied to achieve controllable drug release. [35,36] The differences between the physiological microenvironments and tumor microenvironments, including pH, reduction, and the enzymes that are present, are utilized as endogenous stimuli to trigger the release of loaded drugs.…”

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“…Thus, nanoparticles have gained increasing attention given that the therapeutic index of almost any drug is enhanced through the use of nanotechnologies 11,12 as well as opportunities for non-invasive routes of administration such as oral, nasal and ocular 13 . Additionally, nanoparticles are advantageous as drug carriers due to their high stability; high transport capacity; expediency of both hydrophilic and hydrophobic substance integration; and feasibility of variable routes of administration, including oral administration and inhalation 14 .…”