Improved delivery of PLGA microparticles and microparticle-cell scaffolds in clinical needle gauges using modified viscosity formulations

Qutachi, Omar; Wright, Emma J.; Bray, Gemma; Hamid, Omar A.; Rose, Felicity R.A.J.; Shakesheff, Kevin; Delcassian, Derfogail

Abstract

Polymer microparticles are widely used as acellular drug delivery platforms in regenerative medicine, and have emerging potential as cellular scaffolds for therapeutic cell delivery. In the clinic, PLGA microparticles are typically administered intramuscularly or subcutaneously, with the clinician and clinical application site determining the precice needle gauge used for delivery. Here, we explored the role of needle diameter in microparticle delivery yield, and develop a modified viscosity formulation to improve microparticle delivery across a range of clinically relevent needle diameters. We have identified an optimal biocompatible formulation containing 0.25% pluronic F127 and 0.25% carboxymethyl cellulose, which can increase delivery payload to 520% across needle gauges 21-30G, and note that needle diameter impacts delivery efficacy. We use this formulation to increase the delivery yield of PLGA microparticles, and seperately, PLGA-cell scaffolds supporting viable mesenchymal stem cells (MSCs), demonstrating the first in vitro delivery of this cell scaffold system. Together, these results highlight an optimal formulation for the delivery of microparticle and microparticle-cell scaffolds, and illustrate how careful choice of delivery formulation and needle size can dramatically impact delivery payload.

Citation

Qutachi, O., Wright, E. J., Bray, G., Hamid, O. A., Rose, F. R., Shakesheff, K., & Delcassian, D. (2018). Improved delivery of PLGA microparticles and microparticle-cell scaffolds in clinical needle gauges using modified viscosity formulations. International Journal of Pharmaceutics, 546(1-2), 272-278. https://doi.org/10.1016/j.ijpharm.2018.05.025

• Journal Article Type: Article
• Acceptance Date: May 9, 2018
• Online Publication Date: May 10, 2018
• Publication Date: Jul 30, 2018
• Deposit Date: May 18, 2018
• Publicly Available Date: May 11, 2019
• Journal: International Journal of Pharmaceutics
• Print ISSN: 0378-5173
• Electronic ISSN: 1873-3476
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 546
• Issue: 1-2
• Pages: 272-278
• DOI: https://doi.org/10.1016/j.ijpharm.2018.05.025
• Keywords: High viscosity formulation; Microparticle delivery; Cell particle scaffolds; Needle gauge
• Public URL: https://nottingham-repository.worktribe.com/output/931631
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0378517318303235
• Contract Date: May 18, 2018