Thermoresponsive and mucoadhesive nanogels for intramammary administration of antimicrobial compounds to be employed in bovine mastitis treatment
Bovine mastitis (BM) is the most prevalent disease that affects dairy cows in many countries and it is the most important cause of economic losses in the dairy industry worldwide. The dairy activity is very important for the European economy, producing nearly a quarter of the world’s available milk. Currently, BM control consists mainly of antibiotic therapies. However, they usually cannot eradicate the infection due to acquired drug resistance and survival strategies of bacteria. The mechanisms developed by pathogens are intracellular and biofilm lifestyles that allow them to persist in the mammary gland protected from antibiotic therapies and host immune response. So new therapeutic approaches are needed. The present research project proposes the employment of smart nanogels (NGs) for antimicrobial delivery into mammary gland for BM treatment. The synthesized NGs will present: (i) nanometer size; (ii)thermoresponsive behavior: thermally triggered drug release; (iii) disulfides in their structure: mucoadhesive trigger upon the mucosal environment; (iv) modulated positive charge which will improve their penetration into bacteria biofilms. Several polymers and crosslinker agents will be evaluated to obtain a series of NGs. Defensin 5 and ceftiofur will be studied as antimicrobial agents to entrap into NGs. The virulence mechanisms developed by bacteria are the main responsible for the failure of antimicrobial treatments. Therefore, NGs will be studied and characterized to find suitable nanocarriers with the ability to penetrate bacterial biofilms and internalize host cells, blocking the virulence mechanisms developed by pathogens. Also, the smart drug release lets ensure that the exposition of the host to antimicrobial will be minimum and necessary to kill bacteria. This fact contributes to reducing bacterial resistance development. Nanotechnology in BM treatment is poorly explored which highlight the novelty of the research project proposed.