Vancomycin prolonged release via PLGA system loaded with drug-containing chitosan nanoparticles as a novel in situ forming drug delivery system

Bone infection (Osteomyelitis) is an inflammation of the bone that usually results in infection. Nowadays, in situ forming systems are investigated for the osteomyelitis treatment. These systems are in the form of viscous liquid, but they become solid or semi-solid and the drug is released slowly after injection into the infection site. The aim of present study was the long-term release of vancomycin using a PLGA system loaded with drug-containing chitosan nanoparticles. The in situ formulations formed in this study were composed of three main components: polymer, water-miscible solvent, and active pharmaceutical ingredient. PLGA 504H polymer and PEG 250DME solvent with a polymer to solvent ratio of 3:1 was used to prepare the in situ forming system. Chitosan nanoparticles were designed using gelation ionic method by designing the experiment of chitosan nanoparticles with encapsulation efficiency of 51% and drug loading of 25%. Then, by adding different ratios of released drug to loaded drug through nanoparticles in the system, their release profile was examined. The results revealed that adding chitosan nanoparticles reduced burst release by 44% and increased the release time. In this system, the drug can be added to the polymer solution in different proportions of the free form and the drug-containing nanoparticle. Furthermore, in this system, it is possible to use the combination of different drugs in free form or loaded in nanoparticles to improve the treatment process in the system. The use of biodegradable polymers eliminates the need for surgery in the use of this medicinal system. Moreover, this system is biocompatible and non-toxic due to the non-use of organic solvent in the preparation of the system and the use of PEG 250 DME solvent. KEYWORDS Chitosan; vancomycin; poly lactic-co-glycolic acid (PLGA); in situ forming; bone infection; drug delivery system.