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Beta-Cyclodextrin Modified Mesoporous Bioactive Glass Nanoparticles/Silk Fibroin Hybrid Nanofibers as an Implantable Estradiol Delivery System for the Potential Treatment of Osteoporosis

Abstract

Osteoporosis, a systemic skeletal disease prevalent in elderly women, is associated with post-menopausal estrogen deficiency. Although systemic administration of exogenous estradiol (E2) reduced fragility fractures, the treatment has adverse effects. Localized delivery technologies of E2 could be utilized to circumvent systemic adverse effects of systemic administration. In this study, a localized E2 delivery system is developed. Mesoporous bioactive glass nanoparticles (MBGNPs) with inherent osteogenic properties are modified with β-cyclodextrin (CD-MBGNPs) to enhance its affinity for E2. To ensure mechanical stability and integrity, E2 loaded CD-MBGNPs are further electrospun with silk fibroin (SF) to produce nanofibrous mesh (E2@CD-MBGNPs/SF). The incorporation of MBGNPs in SF enhances in vitro apatite formation and sustains constant release of E2. Moreover, osteoblast proliferation and differentiation markers such as alkaline phosphatase activity, collagen 1 and osteocalcin expression of MC3T3-E1 are augmented in CD-MBGNPs/SF and E2@CD-MBGNPs/SF as compared to SF nanofibers. On the other hand, osteoclast DNA, tartrate resistant acid phosphatase activity and multinucleated cell formation are reduced in E2@CD-MBGNPs/SF as compared to CD-MBGNPs/SF and SF. Hence the presence of CD-MBGNPs in SF stimulates osteoblast function whereas E2 incorporation in CD-MBGNPs/SF reduces osteoclast activity. This is the first report to develop CD-MBGNPs/SF as a localized delivery system for hydrophobic molecule such as estradiol to treat osteoporosis.

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Publication details

The article was received on 29 Jun 2018, accepted on 29 Aug 2018 and first published on 29 Aug 2018


Article type: Paper
DOI: 10.1039/C8NR05268A
Citation: Nanoscale, 2018, Accepted Manuscript
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    Beta-Cyclodextrin Modified Mesoporous Bioactive Glass Nanoparticles/Silk Fibroin Hybrid Nanofibers as an Implantable Estradiol Delivery System for the Potential Treatment of Osteoporosis

    D. Wang, C. Steffi, Z. Wang, C. H. Kong, P. N. Lim, Z. Shi, E. S. Thian and W. Wang, Nanoscale, 2018, Accepted Manuscript , DOI: 10.1039/C8NR05268A

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