Formation of drug nanocrystals under nanoconfinement afforded by liposomes

Research output: Contribution to journalJournal articlepeer-review

Standard

Formation of drug nanocrystals under nanoconfinement afforded by liposomes. / Cipolla, D.; Wu, H.; Salentinig, Stefan; Boyd, Britta; Rades, T.; Vanhecke, D.; Petri-Fink, A.; Rothin-Rutishauser, B.; Eastman, S.; Redelmeier, T.; Gonda, I.; Chan, Hak-Kim.

In: RSC Advances, Vol. 6, No. 8, 2016, p. 6223-6233.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Cipolla, D, Wu, H, Salentinig, S, Boyd, B, Rades, T, Vanhecke, D, Petri-Fink, A, Rothin-Rutishauser, B, Eastman, S, Redelmeier, T, Gonda, I & Chan, H-K 2016, 'Formation of drug nanocrystals under nanoconfinement afforded by liposomes', RSC Advances, vol. 6, no. 8, pp. 6223-6233. https://doi.org/10.1039/c5ra25898g

APA

Cipolla, D., Wu, H., Salentinig, S., Boyd, B., Rades, T., Vanhecke, D., Petri-Fink, A., Rothin-Rutishauser, B., Eastman, S., Redelmeier, T., Gonda, I., & Chan, H-K. (2016). Formation of drug nanocrystals under nanoconfinement afforded by liposomes. RSC Advances, 6(8), 6223-6233. https://doi.org/10.1039/c5ra25898g

Vancouver

Cipolla D, Wu H, Salentinig S, Boyd B, Rades T, Vanhecke D et al. Formation of drug nanocrystals under nanoconfinement afforded by liposomes. RSC Advances. 2016;6(8):6223-6233. https://doi.org/10.1039/c5ra25898g

Author

Cipolla, D. ; Wu, H. ; Salentinig, Stefan ; Boyd, Britta ; Rades, T. ; Vanhecke, D. ; Petri-Fink, A. ; Rothin-Rutishauser, B. ; Eastman, S. ; Redelmeier, T. ; Gonda, I. ; Chan, Hak-Kim. / Formation of drug nanocrystals under nanoconfinement afforded by liposomes. In: RSC Advances. 2016 ; Vol. 6, No. 8. pp. 6223-6233.

Bibtex

@article{eb9f68a8370f443e833d59f37ec121d9,
title = "Formation of drug nanocrystals under nanoconfinement afforded by liposomes",
abstract = "Nanocrystals of drug substances have important therapeutic applications, but their preparation is often difficult due to size control in bottom up approaches, or energetic milling and surface activation in top down processing. In this study, confinement within liposome nanocompartments is demonstrated to enable drug crystallization with a high aspect ratio but limited growth resulting in nanocrystals, using a simple freeze-thaw process which is anticipated to be amenable to large scale preparation. After the freeze-thaw, cryo-transmission electron microscopy (cryoTEM) imaging and cryo-electron tomography revealed that the majority of the liposomes contained a single drug nanocrystal, observed to physically stretch but not burst the liposomes, and the composition of the freeze-thaw medium altered the aspect ratio of the drug nanocrystals. Small angle X-ray scattering and dynamic depolarized light scattering were used to confirm the asymmetric nature of particles in suspension to exclude the cryoTEM preparation process as a contributor to the particle morphology. In assessing potential use in controlled release drug delivery, the in vitro release rate of ciprofloxacin from liposomes containing the nanocrystals revealed that the rate of dissolution of the nanocrystals became the rate controlling step, in contrast to the lipid bilayer rate controlling function prior to the formation of the crystals. The ability to modulate the release rate of the active ingredient in a complex formulation using simple physical means (e.g., freeze/thaw) is an attractive possibility, especially in highly regulated industries such as pharmaceuticals where qualitative and quantitative changes of composition would require extensive safety evaluations.",
author = "D. Cipolla and H. Wu and Stefan Salentinig and Britta Boyd and T. Rades and D. Vanhecke and A. Petri-Fink and B. Rothin-Rutishauser and S. Eastman and T. Redelmeier and I. Gonda and Hak-Kim Chan",
year = "2016",
doi = "10.1039/c5ra25898g",
language = "English",
volume = "6",
pages = "6223--6233",
journal = "RSC Advances",
issn = "2046-2069",
publisher = "RSC Publishing",
number = "8",

}

RIS

TY - JOUR

T1 - Formation of drug nanocrystals under nanoconfinement afforded by liposomes

AU - Cipolla, D.

AU - Wu, H.

AU - Salentinig, Stefan

AU - Boyd, Britta

AU - Rades, T.

AU - Vanhecke, D.

AU - Petri-Fink, A.

AU - Rothin-Rutishauser, B.

AU - Eastman, S.

AU - Redelmeier, T.

AU - Gonda, I.

AU - Chan, Hak-Kim

PY - 2016

Y1 - 2016

N2 - Nanocrystals of drug substances have important therapeutic applications, but their preparation is often difficult due to size control in bottom up approaches, or energetic milling and surface activation in top down processing. In this study, confinement within liposome nanocompartments is demonstrated to enable drug crystallization with a high aspect ratio but limited growth resulting in nanocrystals, using a simple freeze-thaw process which is anticipated to be amenable to large scale preparation. After the freeze-thaw, cryo-transmission electron microscopy (cryoTEM) imaging and cryo-electron tomography revealed that the majority of the liposomes contained a single drug nanocrystal, observed to physically stretch but not burst the liposomes, and the composition of the freeze-thaw medium altered the aspect ratio of the drug nanocrystals. Small angle X-ray scattering and dynamic depolarized light scattering were used to confirm the asymmetric nature of particles in suspension to exclude the cryoTEM preparation process as a contributor to the particle morphology. In assessing potential use in controlled release drug delivery, the in vitro release rate of ciprofloxacin from liposomes containing the nanocrystals revealed that the rate of dissolution of the nanocrystals became the rate controlling step, in contrast to the lipid bilayer rate controlling function prior to the formation of the crystals. The ability to modulate the release rate of the active ingredient in a complex formulation using simple physical means (e.g., freeze/thaw) is an attractive possibility, especially in highly regulated industries such as pharmaceuticals where qualitative and quantitative changes of composition would require extensive safety evaluations.

AB - Nanocrystals of drug substances have important therapeutic applications, but their preparation is often difficult due to size control in bottom up approaches, or energetic milling and surface activation in top down processing. In this study, confinement within liposome nanocompartments is demonstrated to enable drug crystallization with a high aspect ratio but limited growth resulting in nanocrystals, using a simple freeze-thaw process which is anticipated to be amenable to large scale preparation. After the freeze-thaw, cryo-transmission electron microscopy (cryoTEM) imaging and cryo-electron tomography revealed that the majority of the liposomes contained a single drug nanocrystal, observed to physically stretch but not burst the liposomes, and the composition of the freeze-thaw medium altered the aspect ratio of the drug nanocrystals. Small angle X-ray scattering and dynamic depolarized light scattering were used to confirm the asymmetric nature of particles in suspension to exclude the cryoTEM preparation process as a contributor to the particle morphology. In assessing potential use in controlled release drug delivery, the in vitro release rate of ciprofloxacin from liposomes containing the nanocrystals revealed that the rate of dissolution of the nanocrystals became the rate controlling step, in contrast to the lipid bilayer rate controlling function prior to the formation of the crystals. The ability to modulate the release rate of the active ingredient in a complex formulation using simple physical means (e.g., freeze/thaw) is an attractive possibility, especially in highly regulated industries such as pharmaceuticals where qualitative and quantitative changes of composition would require extensive safety evaluations.

U2 - 10.1039/c5ra25898g

DO - 10.1039/c5ra25898g

M3 - Journal article

AN - SCOPUS:84955452678

VL - 6

SP - 6223

EP - 6233

JO - RSC Advances

JF - RSC Advances

SN - 2046-2069

IS - 8

ER -

ID: 179123349