Zoledronic Acid-containing Nanoparticles With Minimum Premature Release Show Enhanced Activity Against Extraskeletal...

Area of Science:

• Nanotechnology
• Oncology
• Pharmacology

Background:

• Bisphosphonates are crucial for treating bone diseases, including bone metastases.
• Nanoparticle formulation of bisphosphonates shows potential for treating extraskeletal tumors by altering pharmacokinetics and biodistribution.
• Existing bisphosphonate nanoparticle formulations suffer from significant premature drug release.

Purpose of the Study:

• To develop a novel nanoparticle formulation of zoledronate (Zol) with reduced premature release.
• To evaluate the efficacy of the new zoledronate nanoparticles (Zol-NPs) in treating extraskeletal tumors.

Main Methods:

• Developed Zol-NPs by encapsulating anionic lipid-coated Zol-calcium nanocomplexes into poly(lactic-co-glycolic) acid nanoparticles.
• Utilized an acid-sensitive cleavable emulsifying agent, octadecanoic acid-hydrazone-polyethylene glycol (2000).
• Assessed Zol release kinetics, cytotoxicity against cancer cells and macrophages, and in vivo tumor distribution and growth inhibition in a mouse model.

Main Results:

• The developed Zol-NPs (approx. 180 nm) exhibited minimal premature Zol release (<5% in 48 h).
• Zol-NPs demonstrated enhanced cytotoxicity towards murine cancer cells and macrophages.
• In vivo studies showed reduced bone distribution and increased tumor distribution of Zol from Zol-NPs, leading to significant tumor growth inhibition compared to free Zol.

Conclusions:

• The novel Zol-NP formulation effectively overcomes the premature release issue of bisphosphonate nanoparticles.
• Zol-NPs show superior efficacy in targeting and inhibiting extraskeletal tumor growth compared to free zoledronate.
• This nanoparticle platform technology holds promise for treating extraskeletal tumors using bisphosphonates.