Tetracycline-grafted PLGA nanoparticles as bone-targeting drug delivery system

Abstract

Purpose Nanoparticles (NPs) that target bone tissue were developed using poly(lactic-co-glycolic acid) (PLGA) copolymers and tetracycline (TC)-based bone-targeting moieties. These NPs are expected to enable the transport of drugs, such as simvastatin (SIM), for the treatment of osteoporosis. Methods The molecular structures of TC–PLGA were validated by 1 H-NMR, and the SIM-loaded NPs were prepared using the solvent emulsification method. The surface properties, cytotoxicity, cellular uptake, cell mineralization, bone targeting potential, and animal pharmacodynamics of the TC–PLGA NPs were evaluated and compared to those of PLGA NPs. Results It was confirmed that the average particle size of the NPs was approximately 220 nm. In phosphate-buffered saline (PBS, pH 7.4), the SIM-loaded NPs exhibited a cumulative release of up to 80% within 72 hours. An in vitro cell evaluation indicated that the NPs had an excellent cellular uptake capacity and showed great biocompatibility with MC3T3-E1 cells, thereby reducing the cytotoxic effects of SIM. The cell mineralization assay showed that the SIM-loaded NPs induced osteogenic differentiation and mineralized nodule formation in MC3T3-E1 cells, thereby achieving the same effect as SIM. Preliminary findings from in vitro and in vivo bone affinity assays indicated that the TC–PLGA NPs may display increased bone-targeting efficiency compared to PLGA NPs lacking a TC moiety. The use of SIM-loaded TC–PLGA NPs in treating osteoporosis was tested through animal pharmacodynamics analyses performed in ovariectomized rats, and the results suggested that the SIM-loaded TC–PLGA NPs can improve the curative effects of SIM on the recovery of bone mineral density compared to either SIM-loaded PLGA NPs or SIM alone. Conclusion Bone-targeting NPs, which were based on the conjugation of TC to PLGA copolymers, have the ability to target bone. These NPs may be developed as a delivery system for hydrophobic drugs, and they are expected to improve the curative effects of drugs, reduce the administered drug doses, and reduce side effects in other organs.

Magnetic Nanoparticles in Bone Tissue Engineering

“…Therefore, it was proposed that this method could be used as an effective targeted drug delivery system for the treatment of osteoporosis induced VCFs [ 44 ]. Interestingly, MNPs can potentially deliver curative osteogenic drugs such as simvastatin [ 45 ] or bone morphogenic protein [ 44 ], a potent osteoinductive growth factor, meaning that this targeting system can be tailored as a bone regenerative treatment for osteoporosis. This clearly has an advantage over therapeutic osteoporosis treatments, which can result in low blood supply to the spine and systemic toxicity of drugs that deposit in healthy tissues.…”

A review and outlook in the treatment of osteosarcoma and other deep tumors with photodynamic therapy: from basic to deep

“…Considering the targeting of osteoporosis, alendronate has potential in targeted therapy in PDT, but the specific mechanism is needed [ 119 ]. Another potential target molecule is tetracycline, which can facilitate PLGA NP adsorption in hydroxyapatite in vitro and reduce distribution to other organs, such as the liver, lungs, and spleen, as well as promoting drug accumulation in the femur and tibia [ 120 ]. Fluoride also presents the possibility of bone targeting, as the same disorders with tetracycline in teeth and skeleton.…”

Sorption Studies of Tetracycline Antibiotics on Hydroxyapatite (001) Surface—A First-Principles Insight

“…The drug can be delivered to the expected target, thus reducing not only the side effects on normal cells but also the dosage and frequency of medication [8,9]. Therefore, bone-specific drug delivery systems for local drug delivery have gained considerable research interest [10][11][12][13].…”

“…Xie et al studied TC-polyethylene glycol-PLGA micelles loaded with atorvastatin to target osteoporosis [10]. A subsequent study on the SIM carrier showed that bone density, bone strength, and bone mineral content were improved [12].…”