Enhanced sucrose-mediated cryoprotection of siRNA-loaded poly (lactic-co-glycolic acid) nanoparticles.

Autor: Youm I; Hough Ear Institute, Oklahoma City, OK, USA., West MB; Hough Ear Institute, Oklahoma City, OK, USA., Huang X; Hough Ear Institute, Oklahoma City, OK, USA., Li W; Hough Ear Institute, Oklahoma City, OK, USA., Kopke RD; Hough Ear Institute, Oklahoma City, OK, USA; Departments of Physiology and Otolaryngology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA. Electronic address: rkopke@houghear.org.
Jazyk: angličtina
Zdroj: Colloids and surfaces. B, Biointerfaces [Colloids Surf B Biointerfaces] 2022 Dec; Vol. 220, pp. 112880. Date of Electronic Publication: 2022 Sep 28.
DOI: 10.1016/j.colsurfb.2022.112880
Abstrakt: The present study aimed to determine the effects of sucrose on the physical stability, cellular entry pathways and functional efficacy of poly(lactic-co-glycolic acid) nanoparticles (PLGA-NPs). PLGA-NPs were synthesized in the absence or presence of 10 % sucrose, using HEI-101, an unmodified small interfering RNA (siRNA), as a drug model. The newly synthesized HEI-101-loaded PLGA-NPs (HEI-101-NPs) were exposed to repeated freeze-thaw cycles and iteratively tested over a six-month evaluation period. The effect of sucrose stabilization on HEI-101-NPs was independently tested in vitro for biocompatibility and cellular uptake in IMO-2B1 cells. Data analyses suggest that, without sucrose, freeze-thaw cycles of HEI-101-NPs resulted in increased particle diameter, increased polydispersity index, and reduced zeta potential. In contrast, a substantial improvement in the physical stability of HEI-101-NPs was observed in the presence of 10 % sucrose. The data revealed that the release of HEI-101 from the PLGA-NPs was governed by polymer erosion and drug diffusion. Data from cellular uptake study in IMO-2B1 cells demonstrated that, 10 % sucrose significantly reduced the inhibitory effect of nocodazole on the microtubule-dependent uptake of PLGA-NPs. In addition, the presence of 10 % sucrose seemed to lessen the inhibitory effect of sodium azide on the energy-dependent uptake of PLGA-NPs. Overall, the current data suggest that the cellular internalization of PLGA-NPs occurred through the polymerization of actin filaments under the control of the microtubules. Our findings reveal cryoprotective effect of 10 % sucrose on HEI-101-NPs that confers marked improvements in the stability, cellular uptake and efficiency for the delivery of biomolecules to inner ear cells.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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