Home Nano Research Article
Article Link
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript
Show Outline
Outline
Graphical Abstract
Abstract
Keywords
References
Show full outline
Hide outline
Research Article

LiF@SiO2 nanocapsules for controlled lithium release and osteoarthritis treatment

Trever Todd1,§, Zhenhui Lu2,§, Jinmin Zhao2,§, Benjamin Cline1, Weizhong Zhang1, Hongmin Chen1,3, Anil Kumar1, Wen Jiang1, Franklin West4, Samuel Franklin5, Li Zheng2(), Jin Xie1()
Department of ChemistryUniversity of GeorgiaAthensGeorgia30602USA
Guangxi Engineering Center in Biomedical Material for Tissue and Organ RegenerationGuangxi Collaborative Innovation Center for BiomedicineGuangxi Key Laboratory of Regenerative MedicineThe First Affiliated Hospital of Guangxi Medical UniversityNanning530021China
Center for Molecular Imaging and Translational MedicineState Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsSchool of Public HealthXiamen UniversityXiamen361102China
Animal Dairy ScienceUniversity of GeorgiaAthensGeorgia30602USA
Department of Small Animal Medicine and SurgeryCollege of Veterinary MedicineUniversity of GeorgiaAthensGeorgia30602USA

§ Trever Todd, Zhenhui Lu, and Jinmin Zhao contributed equally to this work.

Show Author Information

Graphical Abstract

View original image Download original image

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.

Keywords

osteoarthritiscontrolled releasehyaluronic acidlithiumanti-inflammation

References

1

Cho, K.; Wang, X.; Nie, S. M.; Chen, Z. G.; Shin, D. M. Therapeutic nanoparticles for drug delivery in cancer. Clin. Cancer Res. 2008, 14, 1310–1316.

Crossref Google Scholar
2

Farokhzad, O. C.; Langer, R. Impact of nanotechnology on drug delivery. ACS Nano 2009, 3, 16–20.

Crossref Google Scholar
3

Phiel, C. J.; Klein, P. S. Molecular targets of lithium action. Annu. Rev. Pharmacol. Toxicol. 2001, 41, 789–813.

Crossref Google Scholar
4

Corbella, B.; Vieta, E. Molecular targets of lithium action. Acta Neuropsychiatr. 2003, 15, 316–340.

Crossref Google Scholar
5

Ryves, W. J.; Harwood, A. J. Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. Biochem. Biophys. Res. Commun. 2001, 280, 720–725.

Crossref Google Scholar
6

Geddes, J. R.; Burgess, S.; Hawton, K.; Jamison, K.; Goodwin, G. M. Long-term lithium therapy for bipolar disorder: Systematic review and meta-analysis of randomized controlled trials. Am. J. Psychiat. 2004, 161, 217–222.

Crossref Google Scholar
7

Geller, B.; Luby, J. Child and adolescent bipolar disorder: A review of the past 10 years. J. Am. Acad. Child Adolesc. Psychiatry 1997, 36, 1168–1176.

Crossref Google Scholar
8

Hui, W.; Litherland, G. J.; Jefferson, M.; Barter, M. J.; Elias, M. S.; Cawston, T. E.; Rowan, A. D.; Young, D. A. Lithium protects cartilage from cytokine-mediated degradation by reducing collagen-degrading MMP production via inhibition of the P38 mitogen-activated protein kinase pathway. Rheumatology 2010, 49, 2043–2053.

Crossref Google Scholar
9

Minashima, T.; Zhang, Y.; Lee, Y.; Kirsch, T. Lithium protects against cartilage degradation in osteoarthritis. Arthritis Rheumatol. 2014, 66, 1228–1236.

Crossref Google Scholar
10

Thompson, C. L.; Wiles, A.; Poole, C. A.; Knight, M. M. Lithium chloride modulates chondrocyte primary cilia and inhibits hedgehog signaling. Faseb J. 2016, 30, 716–726.

Crossref Google Scholar
11

Lawrence, R. C.; Felson, D. T.; Helmick, C. G.; Arnold, L. M.; Choi, H.; Deyo, R. A.; Gabriel, S.; Hirsch, R.; Hochberg, M. C.; Hunder, G. G. et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the united states. Arthritis Rheum. 2008, 58, 26–35.

Crossref Google Scholar
12

Hunter, D. J.; Neogi, T.; Hochberg, M. C. Quality of osteoarthritis management and the need for reform in the US. Arthrit. Care Res. 2011, 63, 31–38.

Crossref Google Scholar
13

Thompson, C. L.; Yasmin, H.; Varone, A.; Wiles, A.; Poole, C. A.; Knight, M. M. Lithium chloride prevents interleukin-1β induced cartilage degradation and loss of mechanical properties. J. Orthop. Res. 2015, 33, 1552–1559.

Crossref Google Scholar
14

Oruch, R.; Elderbi, M. A.; Khattab, H. A.; Pryme, I. F.; Lund, A. Lithium: A review of pharmacology, clinical uses, and toxicity. Eur. J. Pharmacol. 2014, 740, 464–473.

Crossref Google Scholar
15

Finley, P. R.; Warner, M. D.; Peabody, C. A. Clinical relevance of drug interactions with lithium. Clin. Pharmacokinet. 1995, 29, 172–191.

Crossref Google Scholar
16

Timmer, R. T.; Sands, J. M. Lithium intoxication. J. Am. Soc. Nephrol. 1999, 10, 666–674.

Crossref Google Scholar
17

Evans, C. H.; Kraus, V. B.; Setton, L. A. Progress in intra-articular therapy. Nat. Rev. Rheumatol. 2014, 10, 11–22.

Crossref Google Scholar
18

Gerwin, N.; Hops, C.; Lucke, A. Intra-articular drug delivery in osteoarthritis. Adv. Drug Deliv. Rev. 2006, 58, 226–242.

Crossref Google Scholar
19

Zhang, W.; Ouyang, H. W.; Dass, C. R.; Xu, J. K. Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res. 2016, 4, 15040.

Crossref Google Scholar
20

Brown, T. J.; Laurent, U. B.; Fraser, J. R. Turnover of hyaluronan in synovial joints: Elimination of labelled hyaluronan from the knee joint of the rabbit. Exp. Physiol. 1991, 76, 125–134.

Crossref Google Scholar
21

Schaafsma, G. Calcium in extracellular fluid: Homeostasis. In Calcium in Human Biology. Nordin, B. E. C., Eds. ; Springer: London, 1988; pp 241–259.

Crossref Google Scholar
22

Cox, S. W.; Eley, B. M.; Kiili, M.; Asikainen, A.; Tervahartiala, T.; Sorsa, T. Collagen degradation by interleukin-1β-stimulated gingival fibroblasts is accompanied by release and activation of multiple matrix metalloproteinases and cysteine proteinases. Oral Dis. 2006, 12, 34–40.

Crossref Google Scholar
23

Ning, B.; Wang, P.; Pei X. H.; Kang, Y. Q.; Song, J.; Wang, D. H.; Zhang, W. L.; Ma, R. X. Dual function of β-catenin in articular cartilage growthand degeneration at different stages of postnatal cartilage development. Int. Orthop. 2012, 36, 655–664.

Crossref Google Scholar
24

Marshall, K. W.; Chan, A. D. M. Arthroscopic anterior cruciate ligament transection induces canine osteoarthritis. J. Rheumatol. 1996, 23, 338–343.

Google Scholar
25

Altman, R. D.; Manjoo, A.; Fierlinger, A.; Niazi, F.; Nicholls, M. The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: A systematic review. BMC Musculoskel. Dis. 2015, 16, 321.

Crossref Google Scholar
26

Young, W. Review of lithium effects on brain and blood. Cell Transplant. 2009, 18, 951–975.

Crossref Google Scholar
Nano Research
Volume 11 Issue 10,
October 2018
Pages 5751-5760
DOI: 10.1007/s12274-018-2061-5
Cite this article:
Todd T, Lu Z, Zhao J, et al. LiF@SiO2 nanocapsules for controlled lithium release and osteoarthritis treatment. Nano Research, 2018, 11(10): 5751-5760. https://doi.org/10.1007/s12274-018-2061-5
Part of a topical collection:
NR45 Awards in NanoBiotech, 2018
Metrics & Citations  
Article History
Copyright
Return