Smart injectable nanoparticle-loaded hydrogel for synergic and targeted treatment of osteomyelitis (SinGel)
Aim
Description
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
Progress reports
During the second quarter of the project, work continued on preparing a manuscript regarding the antibacterial activity of phenolic acids and the relationship between this activity and the substances' physicochemical properties. The manuscript has been submitted to the Q1 journal Microbiology Spectrum. Work has commenced on creating conjugates between phenolic acids and selected antibiotics. Preliminary experiments for the synthesis of PLGA nanoparticles were conducted, involving the optimization of the synthesis process and the parameters of the resulting particles—such as size, polydispersity index, and encapsulation efficiency. Two abstracts presenting the project's initial results were submitted to international conferences in the field. Ethical approvals were obtained for the collection of bacterial cultures at TOS. Consequently, the acquisition and testing of clinical isolates began, involving the identification of the pathogens causing the infections. A master's thesis on the project topic was successfully defended. During the RSU Open Day, the project and its objectives were presented, and practical experiments were demonstrated to visitors and prospective students.
During the first quarter of the project, the project team was successfully assembled, and a kick-off meeting was held to discuss key tasks, deadlines, and expected outcomes. Students involved in the project received training on operational procedures and safety protocols for both chemistry and microbiology laboratories. Students and researchers were trained to operate the equipment required to carry out the project tasks. A data management plan was successfully developed. Applications for ethical approval to obtain bacterial cultures from TOS within the scope of the project were submitted. Experiments were conducted to determine the antibacterial and antibiofilm activity of phenolic acids against 10 reference bacterial strains. Work on the first scientific manuscript has started. Project student Daniela Paula Prudņikova participated in the RSU ISC 2026 conference, where she won 3rd place for her oral presentation in the Biochemistry / Pharmacology / Pharmacy / Physiology section.
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)
