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Delivery system | Strategy | Bisphosphonate | Main findings | References |
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Liposomes | Macrophage depletion | Clodronate | Macrophage elimination in the spleen and liver following i.v. administration. | [21–25] |
Liposomes | Macrophage depletion | Clodronate, pamidronate, etidronate | Macrophage elimination in the bloodstream following i.v. administration. | [26] |
Liposomes | Macrophage depletion | Clodronate, pamidronate, etidronate | BPs were found to be even 1000 times less active, compared with the corresponding liposome-based formulations; high calcium extracellular concentration resulted in a stronger macrophage depletion; negatively charged unilamellar liposomes favour macrophage depletion. | [23, 24, 27] |
Liposomes | Macrophage depletion | Clodronate | Macrophage elimination in draining lymph nodes following subcutaneous footpad administration. | [28] |
Liposomes | Macrophage depletion | Clodronate | Intratracheal administration exclusively eliminates macrophages from lung tissues. | [29] |
Liposomes | Macrophage depletion | Clodronate | Enhanced tumor growth in an experimental model of liver metastasis. | [30] |
Liposomes | Macrophage depletion | Clodronate | Inhibition of the tumor growth in different experimental animal models of cancer; reduction of the blood vessel density in the tumor tissue; reduction of the tumor-associated macrophages and tumor-associated dendritic cells. | [31–33] |
Liposomes | Macrophage depletion | Clodronate in combination with sorafenib | Significant inhibition of tumor growth and lung metastasis; reduced tumor angiogenesis. | [34] |
Liposomes | Macrophage depletion | Clodronate as adjuvant agent in radiotherapy | Adjuvant agent in the cancer radiotherapy with delayed tumor regrowth. | [35, 36] |
Liposomes | Macrophage depletion | Clodronate | Reduced metastasis of human prostate cancer in bone. | [37] |
Liposomes | Inhibitory effect on cancer cells | Clodronate | Significant tumor regression. | [38] |
Liposomes | Inhibitory effect on cancer cells | Neridronate | Inhibition of cell growth. | [39] |
PEGylated liposomes | Targeting of extraskeletal tumors | Zoledronate | Enhanced cytotoxic effect in vitro; enhanced inhibition of tumor growth (prostate cancer and multiple myeloma). | [40, 41] |
Folate-coupled PEGylated liposomes | Targeting of extraskeletal tumors | Zoledronate | Enhanced cytotoxic effect in vitro. | [42] |
Self-assembling NPs | Targeting of extraskeletal tumors | Zoledronate | Enhanced cytotoxic effect in vitro; enhanced inhibition of tumor growth (prostate cancer). | [41, 43] |
Superparamagnetic iron oxide nanocrystals | Theranostic purposes | Alendronate, zoledronate | Decrease cell proliferation in vivo and inhibition of tumour growth in vivo, only in combination with a magnetic field. | [44–46] |
Liposomes | Targeting of doxorubicin to bone tumors | Bisphosphonate head group in a novel amphipathic molecule | Increased cytotoxicity in vitro on human osteosarcoma cell line associated to hydroxyapatite. | [47] |
Poly(lactide-co-glycolide) NPs | Targeting of doxorubicin to bone tumors | Alendronate conjugated on the nanocarrier surface | Reduced incidence of metastases associated to a significant reduction of the osteoclast number at the tumor site. | [48] |
Poly(lactide-co-glycolide) NPs | Targeting of docetaxel to bone tumors | Zoledronate conjugated on the nanocarrier surface | Enhanced cytotoxic effect in vitro. | [49] |
Poly(ethylene glycol)-dendrimer | Targeting of paclitaxel to bone tumors | Alendronate conjugated to the nanocarrier | Significant improvement of paclitaxel in vivo half-life. | [50] |
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