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Currently available medications for treating osteoporosis are associated with various adverse effects and resistance issues. Oligonucleotide drugs show great potential. Effective delivery systems are essential to enhance the stability, bioavailability, and targeting of sRNA drugs. Lipid nanoparticles (LNPs) show promise as alternative osteoporosis therapeutics. This study explores the potential of LNPs as an effective delivery system to treat osteoporosis. Methods: LNPs were prepared using microfluidic techniques with varying lipid compositions, and characterized in terms of size, zeta potential, and entrapment efficiency (EE%). Dynamic light scattering (DLS) was employed to determine the size of the LNPs. The zeta potential was measured using electrophoretic light scattering. The pharmacodynamic effects and safety were then evaluated in a mouse model through intravenous administration. Results: Several lipid nanoparticle (LNP) formulations with different nitrogen\/phosphorus ratios and different DMG-PEG2000 ratios were examined, and a lead candidate that supports delivery of sRNA in animal models of osteoporosis was identified. In OVX mice, LNP-sRNA significantly improved bone mineral density (BMD), trabecular microstructure, and biomechanical strength. Safety assessments revealed no systemic toxicity. It is shown that the optimized LNPs can serve as a promising delivery system to mediate sRNA delivery to bone tissue. Conclusions: After comparison of in vitro and in vivo properties, the optimized LNPs demonstrated good comprehensive performance as a delivery system for osteoporosis treatment. These results highlight the potential of the optimized LNPs as an ideal delivery system for osteoporosis, offering improved therapeutic efficacy and reduced systemic side effects.<\/jats:p>","DOI":"10.3390\/pharmaceutics17060789","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T10:45:26Z","timestamp":1750157126000},"page":"789","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Intravenous Administration of sRNA Nanoparticles for Treatment of Osteoporosis in Mice"],"prefix":"10.3390","volume":"17","author":[{"given":"Xuemeng","family":"Mu","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, 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J. Pharm."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s11657-013-0137-0","article-title":"Osteoporosis in the European Union: A compendium of country-specific reports","volume":"8","author":"Svedbom","year":"2013","journal-title":"Arch. Osteoporos."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/S2213-8587(17)30188-2","article-title":"Osteoporosis treatment: Recent developments and ongoing challenges","volume":"5","author":"Khosla","year":"2017","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa1607948","article-title":"Romosozumab treatment in postmenopausal women with osteoporosis","volume":"375","author":"Cosman","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e076898","DOI":"10.1136\/bmj-2023-076898","article-title":"Bisphosphonates","volume":"386","author":"Billington","year":"2024","journal-title":"BMJ"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"707","DOI":"10.20945\/2359-3997000000566","article-title":"Anabolic therapy for osteoporosis: Update on efficacy and safety","volume":"66","author":"Bandeira","year":"2022","journal-title":"Arch. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1111\/bph.15024","article-title":"Overview of treatment approaches to osteoporosis","volume":"178","author":"Langdahl","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/s41587-023-02105-y","article-title":"Rna interference in the era of nucleic acid therapeutics","volume":"42","author":"Jadhav","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41392-020-0207-x","article-title":"Therapeutic sirna: State of the art","volume":"5","author":"Hu","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa1716153","article-title":"Patisiran, an rnai therapeutic, for hereditary transthyretin amyloidosis","volume":"379","author":"Adams","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1208\/s12248-010-9210-4","article-title":"Delivery of sirna therapeutics: Barriers and carriers","volume":"12","author":"Wang","year":"2010","journal-title":"AAPS J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"264","DOI":"10.7555\/JBR.30.20150110","article-title":"Bone site-specific delivery of sirna","volume":"30","author":"Liu","year":"2016","journal-title":"J. Biomed. Res."},{"key":"ref_14","first-page":"207","article-title":"A bone-targeted engineered exosome platform delivering sirna to treat osteoporosis","volume":"10","author":"Cui","year":"2022","journal-title":"Bioact. Mater."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"eade7379","DOI":"10.1126\/sciadv.ade7379","article-title":"Rational polyelectrolyte nanoparticles endow preosteoclast-targeted sirna transfection for anabolic therapy of osteoporosis","volume":"9","author":"Zhang","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1007\/s11427-024-2802-2","article-title":"Potential oligonucleotide drugs in bencao srna atlas (Ii)","volume":"68","author":"Jiang","year":"2025","journal-title":"Sci. China Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1007\/s11427-023-2414-y","article-title":"Potential oligonucleotide drugs in Bencao srna Atlas","volume":"66","author":"Huang","year":"2023","journal-title":"Sci. China Life Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1007\/s11427-022-2181-6","article-title":"Comprehensive analysis of the Bencao (herbal) small Rna Atlas reveals novel Rna therapeutics for treating human diseases","volume":"66","author":"Cao","year":"2023","journal-title":"Sci. China Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s11427-019-9513-y","article-title":"From herbal small Rnas to one medicine","volume":"62","author":"Ji","year":"2019","journal-title":"Sci. China Life Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1002\/iub.2857","article-title":"Bencaosome [16:0 Lyso Pa+Xlgb28-Srna] improves osteoporosis by simultaneously promoting osteogenesis and inhibiting osteoclastogenesis in mice","volume":"76","author":"Du","year":"2024","journal-title":"IUBMB Life"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41573-020-0090-8","article-title":"Engineering precision nanoparticles for drug delivery","volume":"20","author":"Mitchell","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1089\/nat.2018.0721","article-title":"Lipid nanoparticles enabling gene therapies: From concepts to clinical utility","volume":"28","author":"Kulkarni","year":"2018","journal-title":"Nucleic Acid. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"114416","DOI":"10.1016\/j.addr.2022.114416","article-title":"The role of lipid components in lipid nanoparticles for vaccines and gene therapy","volume":"188","author":"Kulkarni","year":"2022","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"34011","DOI":"10.1021\/acsami.0c05489","article-title":"Development of a microfluidic-based post-treatment process for size-controlled lipid nanoparticles and application to sirna delivery","volume":"12","author":"Kimura","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Roces, C.B., Lou, G., Jain, N., Abraham, S., Thomas, A., Halbert, G.W., and Perrie, Y. (2020). Manufacturing considerations for the development of lipid nanoparticles using microfluidics. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12111095"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.2147\/IJN.S44393","article-title":"Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration","volume":"8","author":"Gu","year":"2013","journal-title":"Int. J. Nanomedicine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nm.2617","article-title":"A delivery system targeting bone formation surfaces to facilitate Rnai-based anabolic therapy","volume":"18","author":"Zhang","year":"2012","journal-title":"Nat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"113669","DOI":"10.1016\/j.jconrel.2025.113669","article-title":"Bone marrow vessels are hyperpermeable to macromolecules and nanoscale medicine in a size-dependent manner","volume":"382","author":"Martin","year":"2025","journal-title":"J. Control. Release"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2400505","DOI":"10.1002\/adtp.202400505","article-title":"Hydroxyapatite binding peptide lipid nanoparticles for biomimetic mrna delivery to bone","volume":"8","author":"Choe","year":"2025","journal-title":"Adv. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1016\/j.ymthe.2018.03.010","article-title":"A novel amino lipid series for mrna delivery: Improved endosomal escape and sustained pharmacology and safety in non-human primates","volume":"26","author":"Sabnis","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.addr.2020.11.003","article-title":"Advanced drug delivery 2020\u2014Parts 1,2 and 3","volume":"156","author":"Ghandehari","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6948","DOI":"10.1021\/ja301621z","article-title":"Rapid discovery of potent sirna-containing lipid nanoparticles enabled by controlled microfluidic formulation","volume":"134","author":"Chen","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1038\/mt.2010.85","article-title":"Targeted delivery of rnai therapeutics with endogenous and exogenous ligand-based mechanisms","volume":"18","author":"Akinc","year":"2010","journal-title":"Mol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8529","DOI":"10.1002\/anie.201203263","article-title":"Maximizing the potency of sirna lipid nanoparticles for hepatic gene slencing in vivo","volume":"51","author":"Jayaraman","year":"2012","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1016\/S0140-6736(21)02646-5","article-title":"Drug therapy for osteoporosis in older adults","volume":"399","author":"Reid","year":"2022","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/nnano.2015.330","article-title":"Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers","volume":"11","author":"Becker","year":"2016","journal-title":"Nat. Nanotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1210\/me.2003-0498","article-title":"The Wnt Antagonist Secreted Frizzled-Related Protein-1 Is a Negative Regulator of Trabecular Bone Formation in Adult Mice","volume":"18","author":"Bodine","year":"2004","journal-title":"Mol. Endocrinol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nm.3074","article-title":"Wnt signaling in bone homeostasis and disease: From human mutations to treatments","volume":"19","author":"Baron","year":"2013","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1172\/JCI28551","article-title":"Regulation of bone mass by wnt signaling","volume":"116","author":"Krishnan","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1056\/NEJMoa1708322","article-title":"Romosozumab or alendronate for fracture prevention in women with osteoporosis","volume":"377","author":"Saag","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/s41419-022-05075-2","article-title":"Rna-based therapeutics: An overview and prospectus","volume":"13","author":"Zhu","year":"2022","journal-title":"Cell Death Dis."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/6\/789\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:53:34Z","timestamp":1760032414000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/6\/789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,17]]},"references-count":41,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["pharmaceutics17060789"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17060789","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,17]]}}}