TY - JOUR

T1 - Cisplatin Encapsulation Generates Morphologically Different Multicompartments in the Internal Nanostructures of Nonlamellar Liquid-Crystalline Self-Assemblies

AU - Azmi, Intan Diana Mat

AU - Østergaard, Jesper

AU - Stürup, Stefan

AU - Gammelgaard, Bente

AU - Urtti, Arto

AU - Moghimi, Seyed Moein

AU - Yaghmur, Anan

PY - 2018/6/5

Y1 - 2018/6/5

N2 - Cisplatin ( cis-diamminedichloroplatinum(II)) is among the most potent cytotoxic agents used in cancer chemotherapy. The encapsulation of cisplatin in lipid-based drug carriers has been challenging owing to its low solubility in both aqueous and lipid phases. Here, we investigated cisplatin encapsulation in nonlamellar liquid-crystalline (LC) nanodispersions formed from a ternary mixture of phytantriol (PHYT), vitamin E (Vit E), and an anionic phospholipid [either phosphatidylglycerol (DSPG) or phosphatidylserine (DPPS)]. We show an increase in cisplatin encapsulation efficiency (EE) in nanodispersions containing 1.5-4 wt % phospholipid. The EE was highest in DPPS-containing nanodispersions (53-98%) compared to DSPG-containing counterparts (25-40%) under similar experimental conditions. Through structural and morphological characterizations involving synchrotron small-angle X-ray scattering and cryogenic transmission electron microscopy, we further show that varying the phospholipid content of cisplatin-free nanodispersions triggers an internal phase transition from a neat hexagonal (H2) phase to a biphasic phase (internal H2 phase coexisting with the lamellar (Lα) phase). However, cisplatin encapsulation in both DPPS- and DSPG-containing nanodispersions generates the coexistence of morphologically different multicompartments in the internal nanostructures comprising vesicles as a core, enveloped by an inverted-type surface bicontinuous cubic Im3 m (primitive, QIIP) phase or H2 phase. We discuss the biophysical basis of these drug-induced morphological alterations and provide insights into the potential development of inverted-type LC nanodispersions for cisplatin delivery.

AB - Cisplatin ( cis-diamminedichloroplatinum(II)) is among the most potent cytotoxic agents used in cancer chemotherapy. The encapsulation of cisplatin in lipid-based drug carriers has been challenging owing to its low solubility in both aqueous and lipid phases. Here, we investigated cisplatin encapsulation in nonlamellar liquid-crystalline (LC) nanodispersions formed from a ternary mixture of phytantriol (PHYT), vitamin E (Vit E), and an anionic phospholipid [either phosphatidylglycerol (DSPG) or phosphatidylserine (DPPS)]. We show an increase in cisplatin encapsulation efficiency (EE) in nanodispersions containing 1.5-4 wt % phospholipid. The EE was highest in DPPS-containing nanodispersions (53-98%) compared to DSPG-containing counterparts (25-40%) under similar experimental conditions. Through structural and morphological characterizations involving synchrotron small-angle X-ray scattering and cryogenic transmission electron microscopy, we further show that varying the phospholipid content of cisplatin-free nanodispersions triggers an internal phase transition from a neat hexagonal (H2) phase to a biphasic phase (internal H2 phase coexisting with the lamellar (Lα) phase). However, cisplatin encapsulation in both DPPS- and DSPG-containing nanodispersions generates the coexistence of morphologically different multicompartments in the internal nanostructures comprising vesicles as a core, enveloped by an inverted-type surface bicontinuous cubic Im3 m (primitive, QIIP) phase or H2 phase. We discuss the biophysical basis of these drug-induced morphological alterations and provide insights into the potential development of inverted-type LC nanodispersions for cisplatin delivery.

U2 - 10.1021/acs.langmuir.8b01149

DO - 10.1021/acs.langmuir.8b01149

M3 - Journal article

C2 - 29768016

VL - 34

SP - 6570

EP - 6581

JO - Langmuir

JF - Langmuir

SN - 0743-7463

IS - 22

ER -