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Table 2 Summary of different liposomal formulations

From: Lipid based nanoparticles as a novel treatment modality for hepatocellular carcinoma: a comprehensive review on targeting and recent advances

Drug

Materials used

In vitro

In vivo

Summary

References

Cisplatin

Curcumin

DMPC

1,2-dioleoyl-sn-glycerol-3-phosphate (DOPA)

Cholesterol

DSPE-PEG2000

HepG2

H22 tumor bearing mice

HepG2 tumor bearing mice

High cytotoxic effect on hepG2 cells

Elevated ROS levels

Improved plasma retention time and antitumor effects with lower signs of toxicity in vivo

[313]

Synthetic phosphoethanolamine (amino-ethyl phosphoric ester (lipid precursor) synthesized by the research group)

Dioctadecyldimethyl-ammonium Chloride (DODAC)

Hepa1c1c7

–

Treatment was significantly more effective to promote cell death by apoptosis

Elevated expression of DR4 receptor, caspases-3 and 8, cytochrome c, p53, p21, p27 and Bax

Decreased expression of Bcl-2, cyclin D1, CD90 and CD44 proteins

[314]

Cantharidin

Soy phosphatidylcholine

DSPE-PEG2000

HepG2

HepG2 tumor bearing mice

Enhanced cytotoxicity, apoptosis, and antiproliferative effects

Improved antitumor effects in vivo

[315]

9-Nitrocamptothecin

Egg yolk phosphatidylcholine

Cholesterol

HepG2

Bel-7402

Hep3B

L02

HepG2 tumor bearing mice

High sensitivity of both free and drug loaded liposomes toward HepG2 cells, followed by Bel-7402, while being resistant toward Hep3B

Elevated expression of p53, p21, p27, Bax, caspase-3, caspase-8, caspase-9, and mitochondrion-associated 1

Decreased expression of Bcl-2, cyclin E, cyclin A, Cdk2 and cyclin D1

Augmented antitumor effects with higher safety profile in vivo

[316]

DOX

Salinomycin

HSPC

Cholesterol

DSPE-PEG2000

HepG2

HepG2 tumor bearing mice

High cytotoxic effect in vitro

Better pharmacokinetic parameters including larger AUC, and longer t1/2

Enhanced tumor growth inhibition in vivo

[317]

Galactomannan

Soy phosphatidylcholine

Cholesterol

–

DEN and CCL4 HCC model in rats

Reduced liver enzymes, PI3K/Akt, PTEN, STAT 5A gene expression, and antioxidant biomarker MDA

Elevated glutathione and glutathione S-transferase levels

Significant restoration of the normal hepatic architecture

[318]

Oleanolic acid

Soybean lecithin

Cholesterol

Triolein

Stearic acid

Tween 80

Polyvinyl alcohol

HepG2

H22

Pharmacokinetic and toxicity study in healthy rats

H22 tumor bearing mice

High cytotoxic effect in vitro

Improved pharmacokinetic parameters including longer circulation time

Enhanced tumor suppression and longer survival time in vivo

[319]

Artesunate

Lecithin

Cholesterol

HepG2

LO2

HepG2 tumor bearing mice

Reduced IC50 in vitro with almost no toxicity on normal liver cells

Higher reduction in tumor growth rate and tumor weight in vivo

[320]

–

DSPC

DOPE

DSPE-mPEG2000

C8 PEG750 Ceramide

C8 Ceramide

HepG2

SMMC-7721

Huh7

HL7702

HepG2 tumor bearing mice

High cytotoxic effect on HCC cells while showing minimal effect on normal hepatocytes

Caspase dependent apoptosis, ASK1, and JNK activation while inhibiting AKT-mTOR

Improved antitumor effects in vivo

[321]

di-n-butyl-di-(4-chlorobenzohydroxamato)-tin(IV) (DBDCT)

Soy phosphatidylcholine

Cholesterol

–

Pharmacokinetic and tissue distribution in healthy rats

H22 tumor bearing mice

Augmented pharmacokinetic parameters including larger AUC, and longer t1/2

Enhanced antitumor effects in vivo with higher drug concentration in RES organs and lower concentration in the adrenal glands

[322]

SOR

Gadolinium

Lipoid® E80

Cholesterol

HepG2

H22

H22 tumor bearing mice

Dual acting liposomes as a therapeutic and a visualizing agent

Sustained drug release leading to lower cytotoxicity than free drug

Improved antitumor effects and Magnetic resonance imaging (MRI) visualization with high safety profile in vivo

[323]

–

DMPC

polyoxyethylene(23) dodecyl ether

HepG2

Huh7

HC

–

High cytotoxic effect against HCC cells (high membrane fluidity) with no effect on normal hepatocytes cells (low membrane fluidity)

Caspase-3 mediated apoptosis

[324]

Brucea javanica oil

Lecithin

Cholesterol

HepG2

HepG2 tumor bearing mice

High cytotoxic effect in vitro

Dose dependent reduction in intra-hepatic metastasis with improved survival rates in vivo

[325]

Cordycepin

Soy phosphatidylcholine

Cholesterol

Tween 80

Vitamin E

BEL7402

H22

H22 tumor bearing mice

Sustained drug release leading to lower cytotoxicity than free drug

Dose dependent reduction in tumor growth, and tumor weight in vivo

[326]

2,6-di-isopropylphenol-linolenic acid

Egg phosphatidylcholine

HepG2

DEN HCC model in mice

The prepared drug conjugate exhibited significant cytotoxicity in vitro

The prepared nanoparticles activated macrophages to engulf and suppress tumor cells

Reduction in COX-2, bcl-2 expression

Upregulation in Bax expression

Enhanced antitumor effects with high safety profile in vivo

[327]