Abstract
Liposomes have been widely researched as drug delivery systems; however, the solid state form of drug inside the liposome, whether it is in solution or in a solid state, is often not studied. The solid state properties of the drug inside the liposomes are important, as they dictate the drug release behavior when the liposomes come into contact with physiological fluid. Recently, a new approach of making liposomal ciprofloxacin nanocrystals was proposed by the use of an additional freeze-thawing step in the liposomal preparation method. This paper aims to determine the solid state properties of ciprofloxacin inside the liposomes after this additional freeze-thawing cycle using cryo-TEM, small-angle X-ray scattering (SAXS), and cross-polarized light microscopy (CPLM). Ciprofloxacin precipitated in the ciprofloxacin hydrate crystal form with a unit cell dimension of 16.7 Å. The nanocrystals also showed a phase transition at 93 °C, which represents dehydration of the hydrate crystals to the anhydrate form of ciprofloxacin, verified by temperature-dependent SAXS measurements. Furthermore, the dependence of the solid state form of the nanocrystals on pH was investigated in situ, and it was shown that the liposomal ciprofloxacin nanocrystals retained their crystalline form at pH 6-10. Understanding the solid state attributes of nanocrystals inside liposomes provides improved understanding of drug dissolution and release as well as opening avenues to new applications where the nanosized crystals can provide a dissolution benefit.
| Original language | English |
|---|---|
| Pages (from-to) | 184-194 |
| Number of pages | 11 |
| Journal | Molecular Pharmaceutics |
| Volume | 16 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 7 Jan 2019 |
Keywords
- ciprofloxacin
- cryo-TEM
- liposomes
- nanocrystals
- small-angle X-ray scattering
- solid state
Cite this
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Solid State Characterization of Ciprofloxacin Liposome Nanocrystals. / Li, Tang; Mudie, Stephen; Cipolla, David; Rades, Thomas; Boyd, Ben J.
In: Molecular Pharmaceutics, Vol. 16, No. 1, 07.01.2019, p. 184-194.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Solid State Characterization of Ciprofloxacin Liposome Nanocrystals
AU - Li, Tang
AU - Mudie, Stephen
AU - Cipolla, David
AU - Rades, Thomas
AU - Boyd, Ben J.
PY - 2019/1/7
Y1 - 2019/1/7
N2 - Liposomes have been widely researched as drug delivery systems; however, the solid state form of drug inside the liposome, whether it is in solution or in a solid state, is often not studied. The solid state properties of the drug inside the liposomes are important, as they dictate the drug release behavior when the liposomes come into contact with physiological fluid. Recently, a new approach of making liposomal ciprofloxacin nanocrystals was proposed by the use of an additional freeze-thawing step in the liposomal preparation method. This paper aims to determine the solid state properties of ciprofloxacin inside the liposomes after this additional freeze-thawing cycle using cryo-TEM, small-angle X-ray scattering (SAXS), and cross-polarized light microscopy (CPLM). Ciprofloxacin precipitated in the ciprofloxacin hydrate crystal form with a unit cell dimension of 16.7 Å. The nanocrystals also showed a phase transition at 93 °C, which represents dehydration of the hydrate crystals to the anhydrate form of ciprofloxacin, verified by temperature-dependent SAXS measurements. Furthermore, the dependence of the solid state form of the nanocrystals on pH was investigated in situ, and it was shown that the liposomal ciprofloxacin nanocrystals retained their crystalline form at pH 6-10. Understanding the solid state attributes of nanocrystals inside liposomes provides improved understanding of drug dissolution and release as well as opening avenues to new applications where the nanosized crystals can provide a dissolution benefit.
AB - Liposomes have been widely researched as drug delivery systems; however, the solid state form of drug inside the liposome, whether it is in solution or in a solid state, is often not studied. The solid state properties of the drug inside the liposomes are important, as they dictate the drug release behavior when the liposomes come into contact with physiological fluid. Recently, a new approach of making liposomal ciprofloxacin nanocrystals was proposed by the use of an additional freeze-thawing step in the liposomal preparation method. This paper aims to determine the solid state properties of ciprofloxacin inside the liposomes after this additional freeze-thawing cycle using cryo-TEM, small-angle X-ray scattering (SAXS), and cross-polarized light microscopy (CPLM). Ciprofloxacin precipitated in the ciprofloxacin hydrate crystal form with a unit cell dimension of 16.7 Å. The nanocrystals also showed a phase transition at 93 °C, which represents dehydration of the hydrate crystals to the anhydrate form of ciprofloxacin, verified by temperature-dependent SAXS measurements. Furthermore, the dependence of the solid state form of the nanocrystals on pH was investigated in situ, and it was shown that the liposomal ciprofloxacin nanocrystals retained their crystalline form at pH 6-10. Understanding the solid state attributes of nanocrystals inside liposomes provides improved understanding of drug dissolution and release as well as opening avenues to new applications where the nanosized crystals can provide a dissolution benefit.
KW - ciprofloxacin
KW - cryo-TEM
KW - liposomes
KW - nanocrystals
KW - small-angle X-ray scattering
KW - solid state
UR - http://www.scopus.com/inward/record.url?scp=85058163691&partnerID=8YFLogxK
U2 - 10.1021/acs.molpharmaceut.8b00940
DO - 10.1021/acs.molpharmaceut.8b00940
M3 - Article
VL - 16
SP - 184
EP - 194
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
SN - 1543-8384
IS - 1
ER -