ABSTRACT
The objective of the current study was to create an efficient, minimally invasive combined system comprising in situ forming hydrogel loaded with both spray-dried polymeric nanoparticles encapsulating linezolid and nanohydroxyapatite for local injection to bones or their close vicinity. The developed system was designed for a dual function namely releasing the drug in a sustained manner for long-term treatment of bone infections and supporting bone proliferation and new tissues generation. To achieve these objectives, two release sustainment systems for linezolid were optimized namely a composite in situ forming chitosan hydrogel and spray-dried PLGA/PLA solid nanoparticles. The composite, in situ forming hydrogel of chitosan was prepared using two different gelling agents namely glycerophosphate (GP) and sodium bicarbonate (NaHCO3) at 3 different concentrations each. The spray-dried linezolid-loaded PLGA/PLA nanoparticles were developed using a water-soluble carrier (PVP K30) and a lipid soluble one (cetyl alcohol) along with 3 types of DL-lactide and/or DL-lactide-co-glycolide copolymer using nano-spray-drying technique. Finally, the optimized spray-dried linezolid nanoparticles were incorporated into the optimized composite hydrogel containing nanohydroxy apatite (nHA). The combined hydrogel/nanoparticle systems displayed reasonable injectability with excellent gelation time at 37 °C. The optimum formulae sustained the release of linezolid for 7-10 days, which reveals its ability to reduce the frequency of injection during the course of treatment of bones infections and increase the patients' compliance. They succeeded to alleviate the bone infections and the associated clinical, biochemical, radiological, and histopathological changes within 2-4 weeks of injection. As to the state of art in this study and to the best of our knowledge, no such complete and systematic study on this type of combined in situ forming hydrogel loaded with spray-dried nanoparticles of linezolid is available yet in literatures.
Subject(s)
Chitosan , Nanoparticles , Humans , Linezolid , Hydrogels , PolyestersABSTRACT
Chronic osteomyelitis is a challenging disease due to its serious rates of mortality and morbidity while the currently available treatment strategies are suboptimal. In contrast to the adopted systemic treatment approaches after surgical debridement in chronic osteomyelitis, local drug delivery systems are receiving great attention in the recent decades. Local drug delivery systems using special carriers have the pros of enhancing the feasibility of penetration of antimicrobial agents to bone tissues, providing sustained release and localized concentrations of the antimicrobial agents in the infected area while avoiding the systemic side effects and toxicity. Most important, the incorporation of osteoinductive and osteoconductive materials in these systems assists bones proliferation and differentiation, hence the generation of new bone materials is enhanced. Some of these systems can also provide mechanical support for the long bones during the healing process. Most important, if the local systems are designed to be injectable to the affected site and biodegradable, they will reduce the level of invasion required for implantation and can win the patients' compliance and reduce the healing period. They will also allow multiple injections during the course of therapy to guard against the side effect of the long-term systemic therapy. The current review presents different available approaches for delivering antimicrobial agents for the treatment of osteomyelitis focusing on the recent advances in researches for local delivery of antibiotics.HIGHLIGHTSChronic osteomyelitis is a challenging disease due to its serious mortality and morbidity rates and limited effective treatment options.Local drug delivery systems are receiving great attention in the recent decades.Osteoinductive and osteoconductive materials in the local systems assists bones proliferation and differentiationLocal systems can be designed to provide mechanical support for the long bones during the healing process.Designing the local system to be injectable to the affected site and biodegradable will reduces the level of invasion and win the patients' compliance.
