Title |
Cisplatin Encapsulation Generates Morphologically Different Multicompartments in the Internal Nanostructures of Nonlamellar Liquid-Crystalline Self-Assemblies
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Published in |
Langmuir, May 2018
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DOI | 10.1021/acs.langmuir.8b01149 |
Pubmed ID | |
Authors |
Intan Diana Mat Azmi, Jesper Østergaard, Stefan Stürup, Bente Gammelgaard, Arto Urtti, Seyed Moein Moghimi, Anan Yaghmur |
Abstract |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 30 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 6 | 20% |
Researcher | 4 | 13% |
Other | 3 | 10% |
Student > Ph. D. Student | 3 | 10% |
Professor > Associate Professor | 2 | 7% |
Other | 2 | 7% |
Unknown | 10 | 33% |
Readers by discipline | Count | As % |
---|---|---|
Pharmacology, Toxicology and Pharmaceutical Science | 6 | 20% |
Chemistry | 4 | 13% |
Materials Science | 2 | 7% |
Nursing and Health Professions | 1 | 3% |
Biochemistry, Genetics and Molecular Biology | 1 | 3% |
Other | 1 | 3% |
Unknown | 15 | 50% |