LiF@SiO2 nanocapsules for controlled lithium release and osteoarthritis treatment
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Electrolytes can be taken orally or intravenously as supplements or therapeutics. However, their therapeutic window may exceed the serum toxicity threshold, making systemic delivery a poor option. Local injection is also not adequate due to rapid diffusion of electrolytes. Here, we solved this issue with a nanocapsule technology, comprising an electrolyte nanocrystal as the drug filling and a silica sheath to regulate drug release rates. In particular, we prepared LiF@SiO2 nanocapsules and investigated their potential as a delivery system for lithium, which was shown in recent studies to be an effective therapeutic agent for osteoarthritis (OA). We demonstrated that LiF@SiO2 can extend lithium release time from minutes to more than 60 h. After intra- articular (i.a.) injection into a rat OA model, the nanocapsules reduced the Osteoarthritis Research Society International (OARSI) score by 71% in 8 weeks while inducing no systemic toxicity. Our study opens new doors for improved delivery of electrolyte therapeutics, which have rarely been studied in the past.
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LiF@SiO2 nanocapsules for controlled lithium release and osteoarthritis treatment
Abstract
Electrolytes can be taken orally or intravenously as supplements or therapeutics. However, their therapeutic window may exceed the serum toxicity threshold, making systemic delivery a poor option. Local injection is also not adequate due to rapid diffusion of electrolytes. Here, we solved this issue with a nanocapsule technology, comprising an electrolyte nanocrystal as the drug filling and a silica sheath to regulate drug release rates. In particular, we prepared LiF@SiO2 nanocapsules and investigated their potential as a delivery system for lithium, which was shown in recent studies to be an effective therapeutic agent for osteoarthritis (OA). We demonstrated that LiF@SiO2 can extend lithium release time from minutes to more than 60 h. After intra- articular (i.a.) injection into a rat OA model, the nanocapsules reduced the Osteoarthritis Research Society International (OARSI) score by 71% in 8 weeks while inducing no systemic toxicity. Our study opens new doors for improved delivery of electrolyte therapeutics, which have rarely been studied in the past.
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Acknowledgements
This work was supported by two National Institutes of Health grants (R01EB022596, J. X., and R01NS093314, F. W. and J. X.), one Congressionally Directed Medical Research Programs grant (CA140666, J. X.), one National Science Foundation grant (NSF1552617, J. X.), one University of Georgia–Georgia Regents University seed grant (J. X.), and one University of Georgia Postdoc Research Award grant (H. M. C.). We also thank the National Natural Science Fund of China (No. 81760326, L. Z.), the Distinguished Young Scholars Program of Guangxi Medical University (L. Z.), the Guangxi Science and Technology Major Project (Guike AA17204085, L. Z.), and the Guangxi Scientific Research and Technological Development Foundation (GuikeAB16450003, L. Z.).
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