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Review
. 2019 Jul 1:92:1-18.
doi: 10.1016/j.actbio.2019.05.018. Epub 2019 May 13.

Stimulus-responsive polymeric nanogels as smart drug delivery systems

Sakineh Hajebi  1 , Navid Rabiee  2 , Mojtaba Bagherzadeh  2 , Sepideh Ahmadi  3 , Mohammad Rabiee  4 , Hossein Roghani-Mamaqani  1 , Mohammadreza Tahriri  5 , Lobat Tayebi  6 , Michael R Hamblin  7
Affiliations
Review

Stimulus-responsive polymeric nanogels as smart drug delivery systems

Sakineh Hajebi et al. Acta Biomater. .

Abstract

Nanogels are three-dimensional nanoscale networks formed by physically or chemically cross-linking polymers. Nanogels have been explored as drug delivery systems due to their advantageous properties, such as biocompatibility, high stability, tunable particle size, drug loading capacity, and possible modification of the surface for active targeting by attaching ligands that recognize cognate receptors on the target cells or tissues. Nanogels can be designed to be stimulus responsive, and react to internal or external stimuli such as pH, temperature, light and redox, thus resulting in the controlled release of loaded drugs. This "smart" targeting ability prevents drug accumulation in non-target tissues and minimizes the side effects of the drug. This review aims to provide an introduction to nanogels, their preparation methods, and to discuss the design of various stimulus-responsive nanogels that are able to provide controlled drug release in response to particular stimuli. STATEMENT OF SIGNIFICANCE: Smart and stimulus-responsive drug delivery is a rapidly growing area of biomaterial research. The explosive rise in nanotechnology and nanomedicine, has provided a host of nanoparticles and nanovehicles which may bewilder the uninitiated reader. This review will lay out the evidence that polymeric nanogels have an important role to play in the design of innovative drug delivery vehicles that respond to internal and external stimuli such as temperature, pH, redox, and light.

Keywords: Cancer treatment; Drug delivery; Nanogels; Smart drug release; Stimulus-responsive.

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Figures

Figure 1.
Figure 1.
Schematic representation of cholesterol-bearing xyloglucan (CHXG) nanogels [33]. Copyright Taylor and Francis, reprinted with permission
Figure 2.
Figure 2.
Self-assembled polypeptide nanogels [35]. Copyright American Chemical Society, reprinted with permission
Figure 3.
Figure 3.
OH-functionalized nanogels by ATRP in inverse miniemulsion [7] Copyright American Chemical Society, reprinted with permission
Figure 4.
Figure 4.
Degradation of nanogel and release of drugs [60]. Copyright Elsevier, reprinted with permission
Figure 5.
Figure 5.
Permeation release in nanogel [61] Copyright Elsevier, reprinted with permission
Figure 6.
Figure 6.
multi-functional of stimuli-responsive nanogels via targeted ligands and a hydrophilic shell for clinical applications [74] Copyright Royal Society of Chemistry, reprinted with permission
Figure 7.
Figure 7.
The pH-responsive of poly(l-Asp) derivative nanogels in different pH [91] Copyright Elsevier, reprinted with permission
Figure 8.
Figure 8.
Non-invasive fluorescent imaging of uptake DOX-loaded nanogels or free DOX injected into tumor-bearing nude mice [91] Copyright Elsevier, reprinted with permission
Figure 9.
Figure 9.
Synthesis of quaternized PDMAEMA nanogels [98]. Copyright Elsevier, reprinted with permission
Figure 10.
Figure 10.
Scheme of the targeted DOX release from pH-triggered HA-NGs [99] Permission required?
Figure 11.
Figure 11.
T-responsive nanogel for Fe3O4 encapsulate and water molecules release by increasing temperature [106] Copyright Elsevier, reprinted with permission
Figure12.
Figure12.
Transport of diclofenac from the (vPVCL) multilayer nanohydrogel at temperatures: 25 and 32 °C (a) Responsiveness of the nanohydrogel to the temperature and release of the drug [111] Copyright Elsevier, reprinted with permission
Figure 13.
Figure 13.
Temperature-dependent release of a drug from a nanogel in varying conditions [112] Copyright Elsevier, reprinted with permission
Figure 14.
Figure 14.
post-polymerization modification of PPFPMA with amine modifiers toproduce a redox-responsive nanogels (a), release profiles from nanogels in presence and without GSH (b) [120] Copyright Elsevier, reprinted with permission
Figure 15.
Figure 15.
Schematic illustration of controlled release by a novel CXCR4-ligand modified DOX-encapsulated dextrin nanogel at the tumor site [121] Copyright American Chemical Society, reprinted with permission
Figure 16.
Figure 16.
Saline effects, free AMD, free DOX, DOX-DNG and DOX-AMD-DNG on mouse lung [121] Copyright American Chemical Society, reprinted with permission
Figure17.
Figure17.
Light-responsive HA-CM nanogels for CD44 targeted and remotely controlled DOX delivery. (i) Receptor-mediated endocytosis, and (ii) nanogel swelling and drug release upon light irradiation [132] Copyright Elsevier, reprinted with permission
Figure 18.
Figure 18.
Phase transition and drug release of DOX-PNA conjugates [56] Copyright American Chemical Society, reprinted with permission
Figure 19.
Figure 19.
Cumulative release of methotroxate (MTX) and doxorubicin (DOX) from DOX@MTX loaded pH-responsive P(NIPAAm-MAA-DMAEMAQ) magnetic nanoparticles DOX@MTX@NIPMADM at different pH (4, 5.5 and 7.4) and different temperatures (a) 37°C, and (b) 40°C [134] Copyright Elsevier, reprinted with permission
Scheme 1.
Scheme 1.
Different methods of drug loading [58]. Copyright Elsevier, reprinted with permission
Scheme 2.
Scheme 2.
Copolymers that can be cross-linked with light [128,129]
Scheme 3.
Scheme 3.
Preparation of core cross-linked nanoparticles with pH and redox dual sensitivity [138] Copyright Elsevier, reprinted with permission
See this image and copyright information in PMC

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