Advancements in Nanogels for Enhanced Ocular Drug Delivery: Cutting-Edge Strategies to Overcome Eye Barriers
Abstract
:1. Introduction
2. Barriers to Drug Administration for Ocular Diseases
2.1. Barriers to Drug Absorption into the Eye
2.2. Barriers to Movement to the Target Site
2.3. Barriers to Effect Manifestation at the Target Site
2.3.1. Lipid Bilayer of Cell Membranes
2.3.2. Receptor for Cell Membrane Penetration
3. Recent Progress and Challenges in Overcoming Biological Barriers with Nanomaterials
Delivery Systems | Pros | Cons | Ref |
---|---|---|---|
Liposomes | Sustained drug release, improved bioavailability, biodegradable, biocompatible, and non-immunogenic | Poor stability, leakage, and fusion of drugs | [64,65] |
Solid lipid nanoparticles (SLNs) | Drug loading capability for lipophilic and hydrophilic drugs, suitable for autoclaving sterilization, increased ocular bioavailability, and prolonged ocular retention time | Drug expulsion following polymeric transition during long storage | [66,67] |
Polymeric nanoparticles | Increased ocular penetration, prolonged residence time, and simplicity of change | Burst effect and aggregation of particles and toxicity | [68,69,70,71,72] |
Dendrimer | Improved drug penetration and effectiveness | Blurred vision and loss of eyesight | [73,74,75,76] |
Stimuli-responsive gel | Sustained drug release, improved biocompatibility, and biodegradability, Versatility in design | Limited to smaller molecular weight drugs, poor stability, and temperature sensitivity (difficulty in retaining water) | [77,78,79] |
Inorganic nanoparticle | Improved ocular penetration by small size, controlled release by physical and chemical properties (super-magnetism, photothermal, etc.) | Poor stability, bioavailability | [80,81,82,83] |
3.1. Continual Strategies in Indirect Modulation
3.1.1. Leveraging Mucoadhesion for Effective Drug Adsorption
- Surface modification of electrostatic interaction with mucin
- Harnessing hydrogen bonds with carboxyl groups in mucin for nanocarrier surface modification
- Utilizing covalent bonds with cysteine-rich subdomains in mucin for nanocarrier surface modification
3.1.2. Optimizing Cellular Penetration and Uptake through Surface Interaction Adjustments
- Transforming junction protein–nanocarrier interactions for improved paracellular permeability
- Transforming cell–nanocarrier interactions for improved transcellular permeability
3.2. Improving Nanocarrier Drug Delivery through Specific Ligands as Modulators
3.2.1. Proteins and Short Peptides
3.2.2. Cell-Penetrating Peptides
3.2.3. Aptamers
- Dual role of aptamers: serving as modulators and therapeutic molecules
- Aptamers as surface modifiers in drug carriers
4. Exploring DNA Nanostructures as Innovative Vehicles for Ophthalmic Drug Delivery
4.1. Early DNA Nanostructures
4.1.1. Basic DNA Nanostructures: Polyhedron Assembly System
4.1.2. Hybrid Nanostructures for Stability
4.2. Smart DNA Nanostructures in Therapeutic Drug Delivery
4.2.1. Temperature-Responsive DNA Carrier
4.2.2. pH-Responsive DNA Carrier
4.2.3. Biomarker Molecule-Responsive DNA Carrier
4.3. Perspectives of DNA Nanocarriers for Ocular Drug Delivery
4.4. Challenges in Utilizing DNA Nanocarriers for Ocular Drug Delivery
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Stimulus | Structures | Mechanisms | Target Diseases (Drug) | Ref. | |
---|---|---|---|---|---|
Temperature | DNA based silver nanoclusters | The anti-parallel four-strand structure forming DNA-AgNC is structured as an i-motif including C-quadruplex as the temperature changes. | Cancer (Dox) | [185] | |
DNA-gated mesoporous silica nanocarriers | Change of the amino group on the surface of the MSNs acting as the valve | Cancer (Dox) | [186] | ||
DNA-grafted HA with gold nanorod | NIR-triggered on-demand release of spherical nucleic acids by photo-thermal induced DNA dehybridization | Osteoarthritis (gene therapy) | [187] | ||
DNA based hydrogels loaded with gold or silver nanoparticles | Thermoplastic properties of AuNPs and AuNRs trigger the dehybridization of the DNA duplexes | Cancer (Dox) | [188] | ||
pH | Mg2+ aggregated functional DNAs from RCA (i-motif) | i-motif structure switch in response to pH changes | Cancer (Dox) | [189] | |
MN/MC2 duplex with GNP (i-motif) | Cancer (Dox) | [190] | |||
DNA polymer micelles (Hoogsteen-type triplexes) | Hoogsteen interaction switch in response to pH changes | Cancer (Dox) | [191] | ||
Tetrameric DNA walker (triple-stranded structure) | - (Fluorescence) | [192] | |||
Biomolecule | ATP | Framework nucleic acid (FNA) nanocarriers | ATP aptamer (ABA27) responding to ATP triggers the toehold-mediated strand displacement reaction | - (mRNA) | [193] |
2D MoS2 Nanosheets with DNA | Autonomously disassembled of structures in response to cancer cells’ heightened ATP metabolism | Cancer (Dox) | [194] | ||
DNA hydrogels by aptamer-trigger-clamped hybridization chain reaction | Destruction of the hydrogel through the stimulus-response of ATP | Cancer (cloaking and decloaking of tumor cells) | [195] | ||
GSH | DNA-DOX nanogels formed by Cross-linking kiwifruit-derived DNA | High GSH concentration cleaved the disulfide bonds of DTSSP-cross-linked DNA-DOX NGs | Cancer (Dox) | [196] | |
DNA nanohydrogels were created through a self-assembly process using three kinds of building units | High GSH concentration cleaved the disulfide bonds of building units (Y-shaped monomers and a DNA linker) | Cancer (-) | [197] | ||
DNA nanodevice functionalized with small interfering RNA (siRNA) | Mechanical opening and release of siRNA in response to intracellular GSH; cleaved the disulfide bonds | Cancer (Dox) | [198] | ||
Enzymes | Artificial kinase-mediated cascade nanosystem composed of nanomediator (NM) and nanoeffector (NE) | Protein kinase-catalyzed phosphorylation to secondary mediator DNA | Cancer (Dox) | [199] | |
Nanocarriers with double-stranded DNA and MMP-2 cleavable peptides | (MMP)-2 enzymes overexpressed in tumor tissue cleaved the peptide chain | Lung cancer (Dox) | [200] | ||
Oligonucleotides | Spherical nucleic acid from monodisperse DNA–polymer conjugates | In the present of a particular cytoplasmic genetic marker, two triggers hybridize and release nucleic acid therapeutics. | - (Nucleic acid therapeutics) | [201] | |
Drug delivery platform of carbon dots which were connected to a stem-loop molecular beacon | Overexpressed endogenous microRNA-21 released drugs by competitive hybridization with the molecular beacon | Cancer (Dox) | [202] | ||
Metal ion | Loop size of the DNA hairpin | Formation of Thymine–Hg(II)–Thymine complexes by DNA–Hg(II) interactions | - (detection of mercury(II)) | [203] |
Structures | Effectiveness | Target Diseases | Ref. |
---|---|---|---|
DNA nanoparticles |
| Virus or infections | [230,231] |
Lipid-DNA Nanoparticles |
| Retinal diseases or glaucoma | [232,233,234,235] |
Tetrahedral framework nucleic acids |
| Optic neurodegenerative diseases (gene delivery) | [236,237] |
Plasmid DNA nanoparticles compacted with PEG-substituted lysine 30-mer peptides |
| Retinal diseases | [238,239] |
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Lee, H.; Noh, H. Advancements in Nanogels for Enhanced Ocular Drug Delivery: Cutting-Edge Strategies to Overcome Eye Barriers. Gels 2023, 9, 718. https://doi.org/10.3390/gels9090718
Lee H, Noh H. Advancements in Nanogels for Enhanced Ocular Drug Delivery: Cutting-Edge Strategies to Overcome Eye Barriers. Gels. 2023; 9(9):718. https://doi.org/10.3390/gels9090718
Chicago/Turabian StyleLee, Hyeonah, and Hyeran Noh. 2023. "Advancements in Nanogels for Enhanced Ocular Drug Delivery: Cutting-Edge Strategies to Overcome Eye Barriers" Gels 9, no. 9: 718. https://doi.org/10.3390/gels9090718