Alendronate-decorated biodegradable polymeric micelles for potential bone-targeted delivery of vancomycin

Abstract

Osteomyelitis is a bone infection disease which is caused by bacteria or other germs, and could cause serious impact on the health and working capacity of the patients. Alendronate (ALN) can chelate strongly with the calcium ion of hydroxyapatite (HA) which is commonly used to treat osteoporosis. Nanomedicine has attracted a lot of attention in that the nano-sized carrier can deliver drug molecules to specific site of interest with the aid of targeting moiety and achieve sustained release, resulting in improved therapeutic effect and reduced side effect. In this study, micelles self-assembled from poly(lactic acid-co-glycolic acid)-block-poly(ethylene glycol)-alendronate (PLGA-PEG-ALN) copolymer were prepared for bone-targeted delivery of vancomycin (Van). The chemical structure of PLGA-PEG-ALN was confirmed by proton nuclear magnetic resonance ((1)H-NMR) spectroscopy. The formation of the nanoparticles was characterized by dynamic light scattering, transmission electronic microscopy as well as the critical micelle concentration measurement. Release profiles from the micelles revealed that the conjugation of ALN to the surface of micelle did not pose adverse effect on the drug-loading capacity and release behaviors. The cytotoxicity of Van-loaded PLGA-PEG-ALN micelles as well as the blank micelles was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay toward rat bone marrow stromal cells (rBMSCs) and human embryonic hepatocytes (L02 cells), and results showed that this Van-loaded micelle possesses appropriate cytotoxicity and is safe in the potential treatment of osteomyelitis. The in vitro affinity of PLGA-PEG-ALN micelles to the HA was also confirmed in vitro. The antibacterial effect of Van-loaded PLGA-PEG-ALN micelles was tested against Staphylococcus aureus (SA) which is the main pathogenic bacteria in osteomyelitis, and the results showed that the Van-loaded micelles can effectively inhibit the growth of SA. These results demonstrated that the PLGA-PEG-ALN micelles may be potentially used for the bone targeted delivery of Van.

Development of Bone Targeting Drugs

“…Authors explained that free drug concentration in the medium did not reach the MIC when the concentration in the conjugate was lower than 16 µg/mL. However, this micelle formulation did inhibit the activity of Staphylococcus aureus in the in vivo model of osteomyelitis [ 46 , 47 ].…”

“…BP-conjugated prodrugs of prostaglandin E 2 [ 54 ] and 17β-estradiol [ 43 , 46 , 55 ] were developed in preclinical studies. These studies showed that different types of linkages affected pharmacokinetics and pharmacological effects of the BP-conjugated drug.…”

Physiologic Activity of Bisphosphonates – Recent Advances

“…The most common treatments are antibiotics and surgery to remove portions of bone that are infected or dead. Thus, selective targeting of antibiotics to bone seems to be profitable, and some preliminary attempts to design and obtain osteotropic systems with fluoroquinones, [113,114] vancomycin [115] and rifamycin [116] as active components have been undertaken.…”

Strong Antibacterial Polydopamine Coatings Prepared by a Shaking-assisted Method

“…Nowadays interest in implantation of medical devices has continued to accelerate. However, bacterial infection at the site of implanted medical devices has meanwhile become a serious ongoing problem 1 2 3 4 . Developing surface modification techniques to reduce the attachment of bacteria and kill the bacteria on the device surfaces is hence highly desirable 5 6 7 8 9 .…”