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The composite, in situ forming hydrogel of chitosan was prepared using two different gelling agents namely glycerophosphate (GP) and sodium bicarbonate (NaHCO<jats:sub>3<\/jats:sub>) 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 <jats:sc>dl<\/jats:sc>-lactide and\/or <jats:sc>dl<\/jats:sc>-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\u00a0\u00b0C. The optimum formulae sustained the release of linezolid for 7\u201310\u00a0days, which reveals its ability to reduce the frequency of injection during the course of treatment of bones infections and increase the patients\u2019 compliance. They succeeded to alleviate the bone infections and the associated clinical, biochemical, radiological, and histopathological changes within 2\u20134\u00a0weeks 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.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s13346-023-01384-x","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T16:16:12Z","timestamp":1691165772000},"page":"80-102","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Injectable systems of chitosan in situ forming composite gel incorporating linezolid-loaded biodegradable nanoparticles for long-term treatment of bone infections"],"prefix":"10.1007","volume":"14","author":[{"given":"Reem Khaled","family":"Wassif","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3558-1557","authenticated-orcid":false,"given":"Seham A.","family":"Elkheshen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehab Nabil","family":"Shamma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed S.","family":"Amer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehab","family":"Elhelw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"El-kayal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"issue":"1","key":"1384_CR1","doi-asserted-by":"publisher","first-page":"2392","DOI":"10.1080\/10717544.2021.1998246","volume":"28","author":"RK Wassif","year":"2021","unstructured":"Wassif RK, et al. 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