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Biomimetic Gemcitabine–Lipid Prodrug Nanoparticles for Pancreatic Cancer
Author(s) -
Bulanadi Jerikho C.,
Xue Aiqun,
Gong Xiaojuan,
Bean Penelope A.,
Julovi Sohel M.,
Campo Liliana,
Smith Ross C.,
Moghaddam Minoo J.
Publication year - 2020
Publication title -
chempluschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.801
H-Index - 61
ISSN - 2192-6506
DOI - 10.1002/cplu.202000253
Subject(s) - prodrug , nanomedicine , pancreatic cancer , gemcitabine , toxicity , chemistry , amphiphile , liposome , mesophase , nanoparticle , micelle , materials science , cancer , nanotechnology , biochemistry , organic chemistry , copolymer , medicine , phase (matter) , aqueous solution , polymer
Gemcitabine (Gem) is a key drug for pancreatic cancer, yet limited by high systemic toxicity, low bioavailability and poor pharmacokinetic profiles. To overcome these limitations, Gem prodrug amphiphiles were synthesised with oleyl, linoleyl and phytanyl chains. Self‐assembly and lyotropic mesophase behaviour of these amphiphiles were examined using polarised optical microscopy and Synchrotron SAXS (SSAXS). Gem‐phytanyl was found to form liquid crystalline inverse cubic mesophase. This prodrug was combined with phospholipids and cholesterol to create biomimetic Gem‐lipid prodrug nanoparticles (Gem‐LPNP), verified by SSAXS and cryo‐TEM to form liposomes. In vitro testing of the Gem‐LPNP in several pancreatic cancer cell lines showed lower toxicity than Gem. However, in a cell line‐derived pancreatic cancer mouse model Gem‐LPNP displayed greater tumour growth inhibition than Gem using a fraction (<6 %) of the clinical dose and without any systemic toxicity. The easy production, improved efficacy and low toxicity of Gem‐LPNP represents a promising new nanomedicine for pancreatic cancer.