TY - JOUR
T1 - Mixed micelles of lipoic acid-chitosan-poly(ethylene glycol) and distearoylphosphatidylethanolamine-poly(ethylene glycol) for tumor delivery
AU - Elsaid, Zeeneh
AU - Taylor, Kevin M G
AU - Puri, Sanyogitta
AU - Eberlein, Cath A.
AU - Al-Jamal, Khuloud
AU - Bai, Jie
AU - Klippstein, Rebecca
AU - Wang, Julie Tzu Wen
AU - Forbes, Ben
AU - Chana, Jasminder
AU - Somavarapu, Satyanarayana
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Many chemotherapeutics suffer from poor aqueous solubility and tissue selectivity. Distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG) micelles are a promising formulation strategy for the delivery of hydrophobic anticancer drugs. However, storage and in vivo instability restrict their use. The aim of this study was to prepare mixed micelles, containing a novel polymer, lipoic acid-chitosan-poly(ethylene glycol) (LACPEG), and DSPE-PEG, to overcome these limitations and potentially increase cancer cell internalisation. Drug-loaded micelles were prepared with a model tyrosine kinase inhibitor and characterized for size, surface charge, stability, morphology, drug entrapment efficiency, cell viability (A549 and PC-9 cell lines), in vivo biodistribution, ex vivo tumor accumulation and cellular internalisation. Micelles of size 30–130 nm with entrapment efficiencies of 46–81% were prepared. LACPEG/DSPE-PEG mixed micelles showed greater interaction with the drug (condensing to half their size following entrapment), greater stability, and a safer profile in vitro compared to DSPE-PEG micelles. LACPEG/DSPE-PEG and DSPE-PEG micelles had similar entrapment efficiencies and in vivo tumor accumulation levels, but LACPEG/DSPE-PEG micelles showed higher tumor cell internalisation. Collectively, these findings suggest that LACPEG/DSPE-PEG mixed micelles provide a promising platform for tumor delivery of hydrophobic drugs.
AB - Many chemotherapeutics suffer from poor aqueous solubility and tissue selectivity. Distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG) micelles are a promising formulation strategy for the delivery of hydrophobic anticancer drugs. However, storage and in vivo instability restrict their use. The aim of this study was to prepare mixed micelles, containing a novel polymer, lipoic acid-chitosan-poly(ethylene glycol) (LACPEG), and DSPE-PEG, to overcome these limitations and potentially increase cancer cell internalisation. Drug-loaded micelles were prepared with a model tyrosine kinase inhibitor and characterized for size, surface charge, stability, morphology, drug entrapment efficiency, cell viability (A549 and PC-9 cell lines), in vivo biodistribution, ex vivo tumor accumulation and cellular internalisation. Micelles of size 30–130 nm with entrapment efficiencies of 46–81% were prepared. LACPEG/DSPE-PEG mixed micelles showed greater interaction with the drug (condensing to half their size following entrapment), greater stability, and a safer profile in vitro compared to DSPE-PEG micelles. LACPEG/DSPE-PEG and DSPE-PEG micelles had similar entrapment efficiencies and in vivo tumor accumulation levels, but LACPEG/DSPE-PEG micelles showed higher tumor cell internalisation. Collectively, these findings suggest that LACPEG/DSPE-PEG mixed micelles provide a promising platform for tumor delivery of hydrophobic drugs.
KW - Biodistribution
KW - Cancer
KW - Chitosan
KW - DSPE-PEG
KW - Hydrophobic drug
KW - Mixed micelles
KW - Uptake
UR - http://www.scopus.com/inward/record.url?scp=85014004341&partnerID=8YFLogxK
U2 - 10.1016/j.ejps.2017.02.001
DO - 10.1016/j.ejps.2017.02.001
M3 - Article
AN - SCOPUS:85014004341
SN - 0928-0987
VL - 101
SP - 228
EP - 242
JO - EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
JF - EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
ER -