Abstract
Advances in drug delivery have been accelerated with the addition of polymeric drug carriers. Direct delivery to a target site is a promising step in developing effective drug and gene therapies to treat disease. The efficacy of these drug carriers heavily relies on cell uptake without compromising critical cellular processes that promote cell viability. Drug release from biodegradable polymers is mediated largely by polymer degradation, and therefore the rate of polymer degradation dictates the feasibility of drug delivery applications. Traditionally, poly(caprolactone) (PCL) has only been used in long-term biomedical applications because the degradation time is much slower than other polymers. However, the biocompatibility of this polymer and the potential for longer delivery windows renders it a promising polymer candidate for drug delivery. In this work, we outline sixteen emulsion solvent evaporation preparation methods for PCL nanoparticles and microparticles to develop particles between 300 nm and 1.7 μm and with zeta potentials of -1.8 mV. We further investigated particles in a size range suitable for systemic tumor delivery and inhaled aerosol delivery to determine cell biocompatibility with the polymer in lung adenocarcinoma, endometrial adenocarcinoma, and human embryonic kidney cells. We determined these particles aren’t detrimental to cell viability below particle monolayer coverage atop cells and therefore these formulations hold promise for the next stage of development as sustained-release drug delivery carriers.
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The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
The authors acknowledge the Electron Microscopy Center at the University of Kentucky for SEM images, with particular support from Nicholas Briot, PhD.
Funding
This work was supported by the University of Kentucky Clinical and Translational Sciences funded by the NIH National Center for Advancing Translational Sciences through grant number UL1TR001998. This content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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A.S. and C.R. contributed equally to concept, experimental design, experimental methods, data analysis, manuscript preparation and editing. H.S. conducted experiments and data analysis. B.G. was responsible for conceptualization, manuscript preparation and editing.
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Manning, A.N., Rowlands, C.E., Saindon, H. et al. Tuning the Emulsion Properties Influences the Size of Poly(Caprolactone) Particles for Drug Delivery Applications. AAPS J 25, 100 (2023). https://doi.org/10.1208/s12248-023-00869-4
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DOI: https://doi.org/10.1208/s12248-023-00869-4