Table 2.
Effects of several nano-based drug delivery systems in treating osteoporosis. In nano-based DDSs, the bare NPs can affect bone regeneration by forming a bone matrix or promoting mineralization. In addition, drug-encapsulated NPs can increase the stability of the drug in vivo and decrease side effects from excessive drug delivery. Recently, there have been many studies for the bone tissue targeting of NPs by conjugation and hybridization with peptides, BPs, and lipid-based NPs.
| Ref. No. | Material | Type of carrier | Drug | Effects |
|---|---|---|---|---|
| [69, 72, 75, 81, 84] | Silica NPs | Silica NPs | - | Biocompatibility, increased bone mineral density |
| pentapeptide (GGGGD)-decorated silica NPs | Salmon calcitonin | Increased circulation time and loading efficiency, enhanced bioavailability, sustained release, biocompatibility, biodegradation, avoids the immune system | ||
|
β-cyclodextrin-modified MBGNPs |
17β-estradiol | Sustained drug release, promoted osteogenesis, deposited HA-like layer (Si2+, Ca2+, and P5+) | ||
| Mesoporous silica NPs | Ceria | Stimulated bone forming of OBs and suppressed OC differentiation, modulated deposited HA-like layer solution (Si2+) | ||
| Bioactive glass NPs (60SiO2−36CaO4−P2O5) | lncRNA NRON | Induced production of extracellular vesicles enriched in lncRNAs inhibiting OC differentiation, enhanced bioactivity and biocompatibility | ||
| [90, 93, 95] | Titanium nanotube | O2-anodized titanium nanotubes with chitosan/alendronate/hyaluronic acid layers | Raloxifene | Sustained drug release, strong binding of bone minerals to the titanium implant, promoted bone formation |
| O2-anodized titanium nanotubes | Icariin and strontium | Sustained drug release, biocompatibility | ||
| O2-anodized titanium nanotubes with polydopamine coating | Calcitonin gene-related peptide | Enhanced bioactivity and biocompatibility | ||
| [100–105] | Hydroxyapatite NPs | HA NPs | Zoledronic acid | Increased bone formation |
| HA NPs | Salmon calcitonin | Enhanced bone targeting and penetration of the mucosa layer | ||
| Zinc-HA NPs | Risedronate | Enhanced bone targeting, improved bone properties | ||
| Multilayer of releasable HA NPs | HA | Bioceramics; highly promoted bone regeneration, reinforced mechanical performance, good potential as a bone graft | ||
| Alendronate-modified HA NPs | Alendronate | Enhanced bone targeting, and increased proliferation of pre-OB | ||
| Calcium-rich HA NPs | Calcium | Promoted the osteogenic differentiation of BM-MSC | ||
| [113–115, 118] | Magnetic NPs | Bisphosphonate-conjugated magnetic NPs | Bisphosphonate | Suppressed OC activation |
| H-coated magnetic NPs | HA | Increased adsorbing of fibronectin, promoted osteoblastic differentiation | ||
| HA-coated superparamagnetic NPs | HA | Promoted OB differentiation, inhibited OC differentiation, downregulated expression of genes related to osteoclastic differentiation, prevented bone loss, increased bone mineral density | ||
| gold-coated magnetic NPs | MSC-EVs containing miR-150-5p | Activated the Wnt/β-catenin pathway, enhancing the proliferation and maturation of OBs. | ||
| [128, 129, 131, 134] | Gold NPs | Gold NPs | Alendronate | Enhanced biocompatibility and biostability, no cytotoxicity or genotoxicity, strong bone-surface affinity, stimulated osteoblastogenesis, and suppressed osteoclastogenesis |
| β-cyclodextrin–conjugated gold NPs | Curcumin | Stimulated osteoblastogenesis and suppressed osteoclastogenesis, can carry hydrophobic drugs, increased solubility and stability | ||
| Gold NPs | Vitamin D | Suppressed osteoclastogenesis, increased uptake by macrophages | ||
| Chitosan-modified gold NPs | c-myb gene | Increased DNA stability, suppressed osteoclastogenesis | ||
| [140, 142, 144] | PLGA NPs | Tetracycline-PLGA micelles | Simvastatin | Enhanced bone targeting, increased proliferation of pre-OBs, and increased circulation time |
| PLGA nanocapsules | PEI-RANK-siRNA complex | Increased siRNA stability | ||
| PLGA NPs | Estradiol | High dermal permeability, improved bone mineral density in the bone | ||
| [149, 153] | Gelatin NPs | Gelatin NPs | Zoledronic acid | Increased drug stability, enhanced drug loading via electrostatic interactions, sustained and stable drug release, avoids phagocytosis |
| Gelatin NPs/silk fibroin aerogel | Strontium Ranelate | Sustained drug release, controlled drug degradation, enhanced biocompatibility, suitable mechanical properties | ||
| [157, 158, 161] | Chitosan NPs | Chitosan NPs | Shilajit | Antioxidant bioactivity, decreased the oxidative stress |
| Chitosan NPs | Risedronate | Enhanced biocompatibility and bone targeting and reduced therapeutic dose | ||
| Chitosan NPs | BMP-2 | Stimulated osteoblastogenesis | ||
| [165–168] | Nanogel | Nanoemulsion gels | Lovastatin | Increased biological permeability |
| PIB nanogel scaffolds | Strontium-loaded mesoporous bioactive glass | Sol-gel transition-dependent temperature, enhanced drug release | ||
| CHP nanogels | W9 peptide | Prevented peptide aggregation, increased peptide stability | ||
| Nanogels | Raloxifene-HCl–loaded solid lipid NPs | Enhanced permeation and bioavailability | ||
| [172, 173] | Polyurethane nanomicelles | ASP8-modified nanomicelles | miRNA | Good biocompatibility and encapsulation efficiency, increased miRNA stability, enhanced bone targeting |
| Pentapeptide (SDSSD)-modified nanomicelles | siRNA | Good biocompatibility and encapsulation efficiency, increased siRNA stability, enhanced osteoblast targeting | ||
| [180, 182, 184, 188] | Lipid-based nanocarriers | Solid lipid NPs | Quercetin | Effective multiple delivery routes (oral, intravenous, pulmonary, and transdermal), enhanced bioavailability and drug solubility |
| ASP6-modified lipid NPs | Simvastatin | Bone targeting, enhanced biocompatibility and bioavailability, prevented drug degradation by the extracellular environment, increased water solubility, high drug-loading efficiency, large-scale production | ||
| ASP8-modified lipid-coated PLGA NPs | Odanacatib | Bone targeting, enhanced biocompatibility and bioavailability, prevented drug degradation by endogenous enzymes, high drug-loading efficiency, large-scale production | ||
| Human microvascular endothelial cell membrane- coated PLGA NPs | MSC secretome | inhibited OC differentiation while promoting osteogenic proliferation |
NP: nanoparticle; EVs: Extracellular vesicles; PLGA: Poly lactic-co-glycolic acid; NRON: ncRNA repressor of the nuclear factor of activated T cells; PIB: Poly(N-isopropylacrylamide-co-butyl methylacrylate); CHP: Cholesterol-bearing pullulan; ASP: Aspartic acid oligopeptide; OB: Osteoblast; OC: Osteoclast; HA: Hydroxyapatite; MSC: Mesenchymal stem cell; BMP: Bone morphogenetic protein