Advanced Drug Delivery Systems for Renal Disorders
Abstract
:1. Introduction
2. Kidney Anatomy and Function
3. Renal Pathophysiology
4. Kidney Drug Delivery Barriers
5. Delivery Sites of Renal Drug Delivery Systems
5.1. Glomerular Endothelial Cells
5.2. Glomerular Basement Membrane
5.3. Podocytes
5.4. Mesangial Cells
Targeted Site | Target | Delivery System | Loaded Drug | Size (nm) | Disease | Refs. |
---|---|---|---|---|---|---|
Glomerular endothelial cells | E-selectin | Liposomes conjugated with anti-E-selectin antibodies | Dexamethas-one | 121 ± 20 | Glomerulonephritis | [64] |
Glomerular basement membrane | - | cyclodextrin-containing polymer-based siRNA nanoparticles | siRNA | 60 to 100 | Normal | [81] |
Mesangial cells | - | siRNA-loaded polycationic cyclodextrin nanoparticles (siRNA/CDPNPs) | siRNA | ~70 | Normal | [82] |
Mesangial cells | - | Celastrol-albumin nanoparticles | Celastrol | 95 | (Thy1.1) Nephritis | [83] |
Mesangial cells | - | PEG- (TRX-20)-modified liposomes | Triptolide | 100 | Membranous nephropathy | [84] |
Podocyte | Neonatal Fc receptor | Bovine serum albumin-methylprednisolone conjugate Nanoparticles (BSA633-MP) | Prednisolone | 10 | Nephrotic syndrome | [74] |
Podocyte | VCAM-1 receptor | Lipid-based nanocarrier SAINT-O-Somes | Rapamycin | 128 ± 4 | TNFα-activated podocytes (mimic the inflammatory condition) | [58] |
6. Nanoparticle Factors for Enhanced Renal Accumulation
6.1. Nanoparticle Size
NPs | Size (nm) | Charge (mV) | Renal Accumulation (% ID) 24 h Post Injection * | Renal Clearance (% ID) | Refs. |
---|---|---|---|---|---|
[64Cu]Cu-1,4,7- triazacyclononane-triacetic acid tagged with near-infrared dye (IR800-CW)- silicon NPs | 2.4 ± 0.5 | 100% ID 24 h post injection | [87] | ||
Glutathione-coated gold NPs (GS-AuNPs) Gold NPs coated with glutathione and cysteamine (GC-AuNPs) | GS-AuNPs = 2.1 ± 0.4 GC-AuNPs = 2.9 ± 0.3 | 40-50% ID 24 h post injection | [86] | ||
Cysteine-coated gold NPs | 3.5 ± 0.9 | 8.8 ± 2.0 | More than 50% ID 24 h post injection | [88] | |
Luminescent glutathione coated copper NPs (GS-CuNPs) | 2.2 | 0.6 | 78.5 ± 3.5% ID 24 h post injection | [89] | |
Glutathione-coated silver NPs (GS-AgNPs) Glutathione-coated Au/Ag NPs (GS-Au/AgNPs) Glutathione-coated gold NPs (GS-Au) | ~3.1 | GS-AgNPs = 51.36% ID GS-Au/Ag(1)NPs = 52.99% ID GS-Au/Ag(2)NPs = 48.69% ID GS-AuNPs = 45.57% ID 48 h post injection. | [90] | ||
Core-shell silica-based NPs (C dots) | 3.3 and 6.0 | C dots (3.3 nm) = 73% ID 48 h post injection C dots (6.0 nm) = 64% ID 48 h post injection | [91] | ||
GS-[198Au]AuNPs | 3.0 ± 0.4 | ~50% ID 48 h post injection | [92] | ||
Gold NPs | 1.4 | ~1.9 | [104] | ||
Quantum dots | 5.6 | ~15% ID/g | [105] | ||
Gold NPs | 3.1 | ~15% ID/g | [106] | ||
Carbon nanotubes | 25 | 0.6% ID/g | [94] | ||
PEGylated kidney-targeting peptide amphiphile micelles and PEGylated amphiphile micelles | Targeted micelles = 15 nm Non-targeted micelles = 12 nm | Targeted micelles = ~35% and non-targeted micelles = 26% of total fluorescence, in the kidneys | [95] | ||
Copper sulfide nanodots | 5.6 | +2.9 | 95% ID 24 h post injection | [107] | |
Silicon NPs | 2.4 | +5.4 | 100% ID 24 h post injection | [103] | |
Gold NPs | 2.9 | −27 | 42% ID 24 h post injection | [86] | |
Gold nanoparticles coated with cysteine (Cys-AuNPs) Gold nanoparticles coated with glycine-cysteine (Gly-Cys-AuNPs) | Cys-AuNPs = 2.69 ± 0.46 nm Gly-Cys-AuNPs = 3.12 ± 0.61 nm | Cys-AuNPs = −12.52 Gly-Cys-AuNPs = −27.33 | Cys-AuNPs = 21.5% ID 24 h post injection Gly-Cys-AuNPs = 41.6% ID 24 h post injection | [106] |
6.2. Nanoparticle Surface Charge
6.3. Nanoparticle Shape
NPs | Shape | Size (nm) | Advantage over Control Particles | Refs. |
---|---|---|---|---|
Single walled carbon nanotubes | Rod | 1.2 × 100−1000 | 65% ID increase in renal clearance | [126] |
Malleable poly(glycidyl methacrylate) (L-PGMA) | Rod | 43 | 4.2% ID/g increase in renal accumulation | [128] |
Mesoporous silica NPs | Rod | 159 | 16% renal increase in renal accumulation | [129] |
RNA nanosquare | Square | 10 | 66% increase in renal accumulation | [130] |
Gold nanostar | Star | 55 | ~40% increase in renal accumulation | [131] |
6.4. Material Choice of Nanoparticles
7. Strategies of Renal Drug Delivery Systems
7.1. Small Molecule Prodrugs
7.1.1. Folate-Modified Prodrugs
7.1.2. Sugar-Modified Prodrugs
7.1.3. Amino Acid-Modified Prodrugs
7.2. Antibody Modified Carriers
7.3. Macromolecular Carriers
7.4. Water Soluble Polymeric Carriers
7.5. Nanoparticles
7.6. Liposomes
7.7. Hydrogel
8. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Materials | Size (nm) | Characteristics | Target | Application | Refs. |
---|---|---|---|---|---|
PLGA | 207 ± 5 | Calcium phosphate embedded for plasmid(p)DNA delivery | Kidney | Promising vectors for gene delivery | [175] |
Chitosan | 38–45 | Catechol-derived low molecular weight chitosan/Doxorubicin | Kidney | Renal fibrosis | [176] |
Liposome | 100–150 | pDNA-encapsulating/SS-cleavable and pH-activated lipid | Kidney | Renal cell carcinoma | [177] |
Gold | - | Nanoparticle arrays as biosensor | Kidney | Chronic kidney disease | [178] |
Cationic cyclodextrin | 60–100 | cationic cyclodextrin-containing polymer (CDP)-based siRNA nanoparticles | Glomerular basement membrane | Nucleic acid delivery | [81] |
Functionalized chitosan | 2.2–3.6 | Functionalized chitosan/quantum dot nano-hybrids | Phosphate metabolites | Treating hyperphosphataemic patients Kidney failure | [179] |
low molecular weight chitosan | 75 ± 25 | Chitosan/siRNA nanoparticles | Proximal tubule epithelial cells (PTECs) | Knockdown of specific genes in (ptecs) Kidney diseases | [171] |
Chitosan | 150 | Metformin-loaded chitosan nanoparticles | (Intestines) improve oral bioavailability of metformin | Polycystic kidney disease Chronic kidney disease | [172] |
PLGA-PEG | 200 | FITC-labelled renal tubular-targeting peptide modified PLGA-PEG nanoparticles | Renal proximal tubules | Chronic kidney disease | [173] |
PLGA | 207 ± 5 | Calcium phosphate-embedded PLGA nanoparticles | Embryonic kidney cells | Gene delivery | [175] |
PLGA-PEG | 347.6 ± 21.0 | Poly(lactic-co-glycolic acid) conjugated to polyethylene glycol (PLGA-PEG) nanoparticles | Proximal tubule cells | Targeted drug delivery of renal tubules | [100] |
Gold | 75 ± 25 | PEGylated Gold-based nanoparticles | Mesangium of the kidney | Kidney diseases | [80] |
Dextran dendrimer | 5 | Dextran-based nanoparticles poly(amido amine) dendrimer nanoparticles | Renal tubular epithelial cells | - | [180] |
PEG-PLGA | 77.8 ± 0.5 | Lambda light chains (LCs) attached to PEGylated polylactic-co-glycolic acid (PLGA) nanoparticles | Proximal tubule epithelial cells | Management of non-oncologic/oncologic renal disorders | [181] |
Hydrogel Carrier | Cargo | Route/Target | Refs. |
---|---|---|---|
Hyaluronic acid/collagen/polyethylene glycol hydrogel | Mesenchymal stem cells, and endothelial progenitor cells | Intracapsular injection | [186] |
Chitosan hydrogel | Mesenchymal stem cells | Intracapsular injection | [98] |
Self-assembling peptide hydrogel | Mesenchymal stem cells | Intracapsular injection | [33] |
Biotin/chitosan hydrogels | Mesenchymal stem cells-derived extracellular vesicles | Intracapsular injection | [187] |
(Arginine-Glycine-Aspartate) peptide hydrogel | Mesenchymal stem cells -derived extracellular vesicles | Intracapsular injection | [188] |
Chitosan hydrogel | Nitric oxide-donor enzyme-prodrug system | Intracapsular injection | [189] |
Collagen hydrogel | Extracellular vesicles | Intracapsular injection | [190] |
Peptide hydrogel | Mitochondria antioxidants Mito-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) | Intracapsular injection/ mitochondria | [191] |
PEG hydrogel | Fibroblast growth factor and murine epidermal growth factor | Intracapsular injection | [192] |
Collagen hydrogel | Prostaglandin E2 | Intracapsular injection | [35] |
Micelle-hyaluronic acid hydrogel | Celastrol/anti-transforming growth factor-β1 antibody | Intracapsular injection | [34] |
Folate-conjugated micelle nanoparticles into polyvinyl alcohol MN patches patch | Rhodamine B | Folate receptor targeting | [28] |
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Alallam, B.; Choukaife, H.; Seyam, S.; Lim, V.; Alfatama, M. Advanced Drug Delivery Systems for Renal Disorders. Gels 2023, 9, 115. https://doi.org/10.3390/gels9020115
Alallam B, Choukaife H, Seyam S, Lim V, Alfatama M. Advanced Drug Delivery Systems for Renal Disorders. Gels. 2023; 9(2):115. https://doi.org/10.3390/gels9020115
Chicago/Turabian StyleAlallam, Batoul, Hazem Choukaife, Salma Seyam, Vuanghao Lim, and Mulham Alfatama. 2023. "Advanced Drug Delivery Systems for Renal Disorders" Gels 9, no. 2: 115. https://doi.org/10.3390/gels9020115