Smart injectable nanoparticle-loaded hydrogel for synergic and targeted treatment of osteomyelitis (SinGel)

Osteomyelitis requires long-term antibacterial treatment, but poor vascularization around bone tissues hinders optimal drug delivery. The rapid development of antibacterial resistance, formation of biofilms, intracellular infections, and the need for two operations are urgent unanswered problems associated with osteomyelitis. We propose to provide a three-fold solution. Firstly, we aim to enhance the antibacterial and bone-affinity properties of four antibiotics (AB) - gentamicin, vancomycin, meropenem, ciprofloxacin - by synthesizing AB bisphosphonate conjugates and testing synergy between AB and a panel of phenolic acids (PA) on both reference strains and clinical isolates. Besides their antibacterial and resistance-reversing properties, PA are known antioxidants and, therefore, could reduce the side effects associated with the treatment. Secondly, PLGA and PLGA-alendronate nanocarriers with co-encapsulated synergic combinations of AB and PA will be prepared to achieve sustained release of active agents. Thirdly, the nanocarrier system and free AB will be encapsulated in a thermo sensitive, biodegradable, osteogenic hydrogel matrix. We hypothesize that a three-fold approach would lower the minimal effective concentration of the AB, enhance efficacy against biofilms and intracellular infections, and possibly minimize the development of antibacterial resistance. Lastly, the biodegradable drug delivery system would allow to switch from a two-stage to a single-stage treatment.

Planned results

• Original research articles published in the Q1 or Q2 publications listed in the Web of Science or SCOPUS databases – 2
• Original research articles published in other journals included in the Web of Science or SCOPUS databases, in the social sciences, humanities and arts, including journals included in the ERIH PLUS database – 1
• Scientific databases and datasets prepared according to the FAIR principles – 1
• Project proposal submitted in an international call for research and development projects (competition abroad or submitted by an international consortium) – 1
• Project proposal submitted in a Latvian call for research and development projects – 1

Scientific Team

• Dace Bandere – lead researcher, principal investigator
• Agnese Brangule – lead researcher
• Ingus Skadiņš – lead researcher
• Ance Bārzdiņa – implementer (student)
• Daniela Paula Prudņikova – implementer (student)