The new approach is aimed at osteomyelitis, a serious infection of bone and bone marrow that is among the hardest infectious diseases to treat.
It is usually caused by bacteria such as Staphylococcus aureus or Pseudomonas aeruginosa, and can affect anyone, though it is especially common in children under 13, people recovering from injuries, and patients after surgery.
In severe cases, the disease can lead to bone tissue death, limb amputation, or, in children, growth problems and lasting deformities.
Treatment usually requires weeks of powerful antibiotics such as ciprofloxacin or vancomycin.
That can be difficult because the bacteria may be located in areas of bone poorly supplied with blood, where drugs reach lower concentrations, or inside biofilms, protective layers that make them harder to destroy.
Strong antibiotics can also cause serious side effects, including damage to the kidneys and liver, as well as blood disorders.
To address that problem, Kamila Sadowska, a professor at the Polish Academy of Sciences' Nałecz Institute of Biocybernetics and Biomedical Engineering, worked with researchers from the Faculty of Chemistry of the University of Warsaw, Gdańsk University of Technology, and the Medical University of Lublin to design a carrier that can deliver the drug directly to the site of infection.
Sadowska said the structures have an unusual flower-like form. They are made from two components, one organic and one inorganic. The organic part is a protein, in this case bovine serum albumin, while the inorganic part is usually a metal phosphate.
That combination matters because bone tissue itself has a hybrid structure, with both protein and mineral components. The researchers say that makes the carrier better suited to bind with bone.
Sadowska said the team currently uses bovine serum albumin in the laboratory, but the eventual target is to use human serum proteins or collagen, which occur naturally in mammals.
The choice of the inorganic component is also crucial. Earlier nanoflowers were made with copper ions, but copper can be toxic to the body at higher concentrations, limiting its medical use.
Sadowska’s team had previously worked with calcium phosphate in the form of hydroxyapatite, a natural building block of bone.
In their newest study, they focused on zinc phosphate, which she said forms nanoflower complexes with proteins more readily and improves the efficiency of production, an important factor for real-world use.
The structures form when a water-based metal salt solution is added to a protein solution in phosphate buffer.
Interactions between the metal ions and protein molecules cause the material to organize spontaneously, first into tiny crystallization centers and then into larger flower-like arrangements built from many small “petals.”
The researchers then loaded the nanoflowers with ciprofloxacin, an antibiotic used to treat bacterial infections.
Laboratory analysis showed that the drug was successfully built into the carrier structure.
Tests carried out in vitro, meaning outside a living organism, and in animal models showed that the nanoflowers were able to suppress the growth of harmful bacteria while maintaining low toxicity and good cell tolerance.
Sadowska said the advantage of the method is that when an antibiotic is given systemically, by mouth or intravenously, it spreads through the whole body and affects healthy tissues as well.
In osteomyelitis, reaching a therapeutic concentration at the infection site often requires high doses over a long period, increasing the risk of side effects.
By contrast, the new nanoflower system makes it possible to concentrate the antibiotic directly at the infected site. That could reduce the need for high systemic doses and improve results in cases where bone infections are extensive.
Sadowska added that infections can sometimes affect as much as one-third of a bone’s volume and require surgery to remove infected marrow, leaving behind a tissue defect.
Delivering the antibiotic early at the site of infection could help destroy bacteria more effectively, while the organic-mineral structure of the nanoflowers may also support bone regeneration and speed healing.
(rt/gs)
Source: naukawpolsce.pl