Mixed micelles of lipoic acid-chitosan-poly(ethylene glycol) and distearoylphosphatidylethanolamine-poly(ethylene glycol) for tumor delivery.
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 30-130nm 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.
UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom. Electronic address: elsaid_a@hotmail.com.
Zeeneh
Z
Elsaid
UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
Kevin M G
KM
Taylor
AstraZeneca, Macclesfield, Cheshire East SK10 2NA, United Kingdom.
Sanyogitta
S
Puri
AstraZeneca, Macclesfield, Cheshire East SK10 2NA, United Kingdom.
Cath A
CA
Eberlein
Kings College London, Franklin-Wilkins Building, Stamford Street, London SE1 8WA, United Kingdom.
Khuloud
K
Al-Jamal
Kings College London, Franklin-Wilkins Building, Stamford Street, London SE1 8WA, United Kingdom.
Jie
J
Bai
Kings College London, Franklin-Wilkins Building, Stamford Street, London SE1 8WA, United Kingdom.
Rebecca
R
Klippstein
Kings College London, Franklin-Wilkins Building, Stamford Street, London SE1 8WA, United Kingdom.
Julie Tzu-Wen
JT
Wang
Kings College London, Franklin-Wilkins Building, Stamford Street, London SE1 8WA, United Kingdom.
Ben
B
Forbes
Kings College London, Franklin-Wilkins Building, Stamford Street, London SE1 8WA, United Kingdom.
Jasminder
J
Chana
UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom. Electronic address: s.somavarapu@ucl.ac.uk.
Satyanarayana
S
Somavarapu
D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D006801:Humans; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008823:Micelles; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D014018:Tissue Distribution / Q000187:drug effects
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D010714:Phosphatidylethanolamines; D011108:Polymers; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D048271:Chitosan
Biodistribution; Cancer; Chitosan; DSPE-PEG; Hydrophobic drug; Mixed micelles; Uptake