Lubricant Strategies in Osteoarthritis Treatment: Transitioning from Natural Lubricants to Drug Delivery Particles with Lubricant Properties
Abstract
:1. Introduction
2. Structural Components of Articular Joints
3. Articular Cartilage Lubrication Mechanism
4. The Role of Cartilage Lubrication in Osteoarthritis Pathogenesis
5. Natural Lubricants Based on HA and Its Hydrogel-Formulated Derivatives
6. Innovative Hydrogel-Based Strategies for Lubrication and Drug Delivery
- a.
- Non-HA-based Hydrogels with superior Lubricant features:
- b.
- Micro-gels and Nano-gels
Name and Microparticle Structure | Material | Size | Outcomes | Ref. |
---|---|---|---|---|
GelMA@DMA-MPC | GelMA microspheres coated with DMA-MPC and loaded with DC | 150 µm | GelMA@DMA-MPC showed enhanced lubrication and sustained drug release of DC. Injected into rat knee joints with osteoarthritis, they showed significant therapeutic effects. | [79] |
MGS@DMA-SBMA | GelMA microspherese coated with DMA-SBMA and loaded with DC | 100 µm | MGS@DMA-SBMA demonstrated improved lubrication abilities and provided chondroprotection both in vitro and in vivo in an OA rat model. | [80] |
RAPA@Lipo@HMS | RAPA-liposome– incorporating HA–based HMs | 200 µm | RAPA@Lipo@HMs enhanced joint lubrication with a smooth rolling mechanism and continuous exposure of liposomes on the surface, forming self-renewing hydration layers through friction. | [81] |
µPlate | PLGA | 20 µm | Drug depot with sustained release; mechanical support to the joint; small molecules delivery. | [82,83] |
Name and Nanoparticle Structure | Material | Size | Outcomes | Ref. |
---|---|---|---|---|
SB-g-NBrMGs | PSPMK brushes-grafted PNIPAAm microgel | ~500 nm | These hairy microgels showed notable tribological properties and temperature-triggered drug release ability. | [86] |
HA-PNIPAM | HA-grafted PNIPAM | ~200 nm | Improved injectability, sensitivity to enzymatic degradation, and cytocompatibility. Prolonged joint retention joint, cartilage protection and reduction of pro-inflammatory cytokines. | [87] |
PNIPAM-PMPC | PNIPAM PMPC | ~200 nm | Resistant to high pressure, efficient DDS for DC, able to control the thermo-sensitive drug release. | [88] |
Chitosan NP | Chitosan NP grafted with hydrophilic sulfonic acid groups. | ~160 nm | Low friction coefficient (µ = 0.01) and valuable DDS. | [89] |
PSBMA-CBPXGSB1/5 | Xanthan gum PSBMA Collagen II-Binding peptide | ~280 nm | Good lubrication proprieties. | [90] |
mega HPGs | Hyper-branched glycerol polymers | ~20–50 nm | High water solubility and low intrinsic viscosity. | [91] |
7. Innovative Liposome-Based Strategies for Drug Delivery and Lubrication
8. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AZO | azobenzene |
CD-PMPC | β-cyclodextrin (CD)-modified poly(2-methacryloyloxyethyl phosphorylcholine) |
DC | dicolfenac |
DDS | drug delivery systems |
DEX | dexamethasone |
DMA-MPC | dopamine methacrylamide-2-methacryloyloxyethylphosphorylcholine |
DMA-SBMA-pSBMA | dopamine methacrylamide-sulfobetaine methacrylate |
DMAA | HEMA and N, N-dimethylacrylamide |
DMM | destabilization of the medial meniscus |
DMPC | 1,2-dimyristoyl-sn-glycero-3-phosphocholine |
DOPC | dioleoyl-sn-glycero-3-phosphatidylcholine |
DOPG | l,2-dioleoyl-sn-glycero-3-phosphoglycerol |
DOTAP | 1,2-DioleOyl-3-TrimethylAmmonium Propane |
DPPC | 1,2-dipalmitoyl-sn-glycero-3-phosphocholine |
DPPE | dipalmitoyl phosphatidylethanolamine |
DS | diclofenac sodium |
DSP | dexamethasone sodium phosphate |
ECM | extracellular matrix |
FDA | Food and Drug Administration |
FLS | type B fibroblast-like synoviocytes |
GAG | glycosaminoglycans |
GelMA | gelatin methacryalate |
HA | hyaluronic acid |
HA-PNIPAM | HA-poly(N-isopropylacrylamide) |
HPG | hyperbranched glycerol polymers |
HSPC | hydrogenated soy phosphatidylcholine |
IA | intra-articular |
IL | interleukin |
Liss Rhod PE | 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine |
MLS | macrophage-like synoviocytes |
MLV | multilamellar vesicles |
MMPs | matrix metalloproteinases |
MP | microparticles |
MSNs | mesoporous silica NP |
MSNs-NH2@PMPC | poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-grafted MSNs |
MSNs-NH2@PSPMK | poly(2-methacryloyloxyethyl phosphorylcholine) (PSPMK)-grafted MSNs |
MT | mitochondria |
MW | molecular weight |
NP | nanoparticles |
NSAID | Non-Steroidal Anti-Inflammatory Drug |
OA | osteoarthritis |
OARSI | Osteoarthritis Research Society International |
PAMPS | poly-2-acrylamide-2-methylpropanesulfonic |
PE | phosphatidylEthanolamine |
PEG | poly(ethylene glycol) |
PGs | proteoglycans |
PG | prostaglandin |
pHEMA | poly(hydroxyethylmethacrylate) |
PL | phospholipids |
PLGA | Poly lactic-co-glycolic acid |
PMS | poly(2-methacryloyloxyethyl phosphorylcholine) (MPC)-co-poly(sulfobetaine methacrylate) (SBMA) hydrogel |
PMPC | poly-2-methacryloyloxyethyl phosphoryl choline |
PNIPAAm | poly(3-sulfopropyl methacrylate potassium salt) (PSPMK) brushes grafted onto poly(N-isopropylacrylamide) |
PNIPAM-PMPC PSBMA | poly[N-isopropylacrylamide-2-methacryloyloxyethyl phosphorylcholine] (PNIPAM-PMPC) |
PSBMA | poly(sulfobetaine methacrylate) |
PSPMK | poly(3-sulfopropyl methacrylate potassium salt) |
RA | rheumatoid arthritis |
RNS | Reactive Nitrogen Species |
ROS | Reactive Oxygen Species |
SB-g-NBrMGs | poly(3-sulfopropyl methacrylate potassium salt) (PSPMK) brushes grafted poly(N-isopropylacrylamide)(PNIPAAm) micro-gels |
SF | synovial fluid |
SUV | single unilamellar vesicles |
VEGF | Vascular Endothelial Growth Factor |
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Lubricant | Structure | Properties | Concentration (mg/mL) | |
---|---|---|---|---|
Healthy | Osteoarthritis | |||
Hyaluronic Acid | Repeating disaccharide units of D-glucuronic acid and D-N-acetylglucosamine attached by β (1–4) and β (1–3) glycosidic bonds | HA creates the backbone for PGs of the ECM, protects the cartilage, and blocks the loss of PGs from the cartilage matrix into the synovial space maintaining the physical form of the ECM. | 1.6–3.7 | 1.1–1.9 |
Lubricin | It is composed by a central mucin-like domain with negatively charged and hydrophilic properties, between two non-glycosylated with positively charged and hydrophobic properties | In the outer superficial zone and at the cartilage surface it interacts with and immobilizes HA | 0.305–0.404 | 0.108–0.183 |
Phospholipids | Amphiphilic molecules with two hydrophobic diacyl tails and a hydrophilic phosphocholine head group | These exposed groups slide past similar groups from the opposing surface with low friction up to high pressures (100 atm or more) via the hydration lubrication mechanism | 0.13–0.15 | 0.23–0.98 |
Physiological effects |
Maintenance of SF viscoelasticity Maintenance of cartilage bio-lubrication Backbone of cartilage ECM |
Pharmacological effects |
Scavenges ROS/RNS and exerts antioxidative effect Exerts anti-inflammatory effect Reduces production of MMPs (MMP-1, MMP-3, and MMP-13) Reduces production and activity of IL-1β, and other pro-inflammatory mediators Inhibits synthesis of PGE2 and bradykinin Regulates fibroblast proliferation Inhibits migration and aggregation of leukocyte and macrophages Enhances synthesis of chondrocytes, HA, and PG Improves viscoelasticity and enhances lubricating potential Improves joint function, mobility, and reduces stiffness |
Product | Molecular Weight kDa | Dose (mg) | Frequency | Cross-Linking |
---|---|---|---|---|
Hyalgan | 500–730 | 20 (5 doses) | Weekly | No |
Supartz FX | 620–1170 | 25 (5 doses) | Weekly | No |
Monovisc | 1000–2900 | 88 (1 dose) | Once | Yes |
Orthovisc | 1000–2900 | 30 (3-4 doses) | Weekly | No |
Euflexaa | 2400–3600 | 20 (3 doses) | Weekly | No |
Synivisc | 6000 | 16 (3 doses) | Weekly | Yes |
Durolane | 100,000 | 60 (1 dose) | Once | No |
Gel-one | ∞ | 30 (1 dose) | Once | Yes |
Synivisc-One | ∞ | 48 (1 dose) | Once | Yes |
Name and Nanoparticle Structure | Material | Size | Outcomes | Ref. |
---|---|---|---|---|
MSNs@pSBM-3 | MSNs grafted with pSBMA-3 | ~100 nm | Improved lubrication properties (μ = 0.045) and reduction of 80% in the coefficient of friction when compared with MSNs (μ = 0.221). | [92] |
PSPMA-g-HSNPs-0.5% | Core/shell charged polymer brush-grafted hollow MSNs | ~739 nm | Controlled drug loading and release; good lubricant effect (μ = 0.173) and reduced coefficient of friction. | [93] |
MSNs@lip | Phospholipid-coated MSNs | 150–350 nm | Reduced coefficient of friction (μ = 0.05) in comparison with MSNs (μ = 0.2). | [94] |
MSNs-NH2@PMPC | PMPC-grafted MSNs | ~260 nm | Enhanced lubrication (μ = 0.015) activity. | [95] |
bMSNs-AZO/CD-PMPC | MSNs modified surface with AZO and CD-PMPC | ~150 nm | Improved lubrication (μ < 0.04) and enhanced drug release efficiency upon visible light irradiation. | [96] |
MSNs-NH2@PSPMK | PSPMK-grafted MSNs | ~114 nm | Great drug loading capability and controlled release, enhanced lubrication in the joint (µ ~ 0.065), and chondrocytes protection. | [97] |
Name/Developer and Liposome Structure | Material | Size | Outcomes | Ref. |
---|---|---|---|---|
TLC599 | DOPC DOPG Cholesterol DSP Dexametason | ~150 nm | Long-lasting profile remaining up to 120 days in synovial joint after a single AI in preclinical study in dogs. | [103] |
Collagomer | DPPE Collagen I Diclofenac | ~10 µm | Significant reduction of inflammation in a rat model of OA. | [104] |
Corciulo, et al. | PC Cholesterol | ND | Significant decrease of OA cartilage damage in a murine model of obesity induced OA. | [105] |
Kim et al. | PE DOTAP Liss Rhod PE Mitochondria | 600–700 nm | Significant decrease of inflammatory cytokines; significant increase in ECM components expression. | [106] |
Zhong et al. | HSPC DSPE-PEG2000 Cholesterol Meloxicam | 110–125 nm * | Reduced ECM degeneration and reduced synthesis of inflammatory factors in mandibular ramus of rats. | [115] |
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Fragassi, A.; Greco, A.; Palomba, R. Lubricant Strategies in Osteoarthritis Treatment: Transitioning from Natural Lubricants to Drug Delivery Particles with Lubricant Properties. J. Xenobiot. 2024, 14, 1268-1292. https://doi.org/10.3390/jox14030072
Fragassi A, Greco A, Palomba R. Lubricant Strategies in Osteoarthritis Treatment: Transitioning from Natural Lubricants to Drug Delivery Particles with Lubricant Properties. Journal of Xenobiotics. 2024; 14(3):1268-1292. https://doi.org/10.3390/jox14030072
Chicago/Turabian StyleFragassi, Agnese, Antonietta Greco, and Roberto Palomba. 2024. "Lubricant Strategies in Osteoarthritis Treatment: Transitioning from Natural Lubricants to Drug Delivery Particles with Lubricant Properties" Journal of Xenobiotics 14, no. 3: 1268-1292. https://doi.org/10.3390/jox14030072
APA StyleFragassi, A., Greco, A., & Palomba, R. (2024). Lubricant Strategies in Osteoarthritis Treatment: Transitioning from Natural Lubricants to Drug Delivery Particles with Lubricant Properties. Journal of Xenobiotics, 14(3), 1268-1292. https://doi.org/10.3390/jox14030072