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Download fileDimeric Artesunate–Phosphatidylcholine-Based Liposomes for Irinotecan Delivery as a Combination Therapy Approach
journal contribution
posted on 2021-09-02, 02:03 authored by Wei He, Yawei Du, Tao Wang, Ji Wang, Lei Cheng, Xinsong LiIn this work, dimeric artesunate–phosphatidylcholine
conjugate
(dARTPC)-based liposomes encapsulated with irinotecan (Ir) were developed
for anticancer combination therapy. First, dARTPC featured with unique
amphipathic properties formed liposomes by classical thin-film methods.
After that, Ir was encapsulated into dARTPC-based liposomes (Ir/dARTPC-LP)
by the triethylammonium sucrose octasulfate gradient method. Physicochemical
characterization indicated that Ir/dARTPC-LP had a mean size of around
140 nm and a negative ζ potential of approximately −30
mV. Most noticeably, liposomes displayed an encapsulation efficiency
of greater than 98% with a controllable drug loading of 4–22%.
The in vitro release of dihydroartemisinin (DHA) and Ir from Ir/dARTPC-LP
was investigated by dialysis in different media. It was found that
effective release of both DHA (65.42%) and Ir (77.28%) in a weakly
acidic medium (pH 5.0) after 48 h was achieved in comparison to very
slow release under a neutral environment (DHA 9.90% and Ir 8.72%),
indicating the controllable release of both drugs. Confocal laser
scanning microscopy confirmed the improved cellular internalization
of Ir/dARTPC-LP. The cytotoxicity of Ir/dARTPC-LP was evaluated in
the MCF-7, A549, and HepG2 cell lines. The results showed that Ir/dARTPC-LP
had significant synergistic efficacy in the loss of cell growth. In
vivo anticancer evaluation was performed using a 4T1 xenograft tumor
model. Ir/dARTPC-LP had a high tumor inhibition rate of 62.7% without
significant toxicity in comparison with the injection of Ir solution.
Taken together, dARTPC encapsulated with Ir has great potential for
anticancer combination therapy.
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without significant toxicityweakly acidic mediumvivo anticancer evaluationsignificant synergistic efficacyphysicochemical characterization indicatedimproved cellular internalizationcombination therapy approacharound 140 nmanticancer combination therapy72 %), indicatingnegative ζ potentialhepg2 cell linescontrollable drug loadinggreat potentialcontrollable releasecell growthvitro releasetaken togetherslow releaseresults showedph 5performed usingneutral environmentmean sizeliposomes displayedfilm methodsencapsulation efficiencyeffective releasedifferent mediaclassical thinbased liposomes48 h42 %)28 %)