Time-Release Microcapsules Deliver Anti-Inflammatory Hormone to Repair Cartilage Damaged by Osteoarthritis

Microcapsules loaded with C-type natriuretic peptide (CNP) have been shown to reduce the type of inflammation characteristic of osteoarthritis (OA) in a model system based on the culture of animal cartilage tissue.

CNP is processed proteolytically to form a secreted hormone of the natriuretic peptide family. The hormone regulates the growth and differentiation of cartilaginous growth plate chondrocytes and may also be vasoactive (causing constriction or dilation of blood vessels) and natriuretic (inhibiting reabsorption of cations, particularly sodium, from urine). Chondrocytes have the potential to repair cartilage damage observed in (OA), but developing treatments for OA based on CPN has been challenging due to poor targeting and difficulty in delivery of the hormone, which readily breaks down in vivo.

To overcome the problems of targeting and delivery, investigators at Queen Mary University of London (United Kingdom) prepared polyelectrolyte microcapsules loaded with CNP and examined whether a layer-by-layer (LbL) approach could have protective effects in cartilage explants treated with the pro-inflammatory cytokine, interleukin-1beta (IL-1beta). The two-micrometer in diameter microcapsules comprised individual CNP-containing layers that released the hormone slowly over time.

Results published in the January 4, 2015, online edition of the journal Biomacromolecules revealed that images obtained by SEM (scanning electron microscopy) showed uniform, spherical microcapsules two to three micrometers in diameter with morphological characteristic similar to templates loaded with or without CNP. The protein was localized around the external surface of the microcapsules with encapsulation efficiencies more than 82.9%. CNP release profiles were broadly similar following nine days of culture. The presence of CNP microcapsules did not significantly affect cell viability (80%) with DNA values that remained stable throughout the culture conditions. Treatment of cartilage explants with CNP microcapsules led to concentration-dependent inhibition of nitric oxide (NO) release in response to IL-1beta and restoration of matrix synthesis.

The results demonstrated the potential for controlled delivery of CNP to dampen pro-inflammatory effects induced by IL-1beta in cartilage explants and to promote cartilage repair in vivo.

Senior author Dr. Tina Chowdhury, associate professor of bioengineering at Queen Mary University of London, said, "If this method can be transferred to patients it could drastically slow the progression of osteoarthritis and even begin to repair damaged tissue. CNP is currently available to treat other conditions such as skeletal diseases and cardiovascular repair. If we could design simple injections using the microcapsules, this means the technology has the potential to be an effective and relatively cheap treatment that could be delivered in the clinic or at home."

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Queen Mary University of London