Table 7.
Long-circulating liposomes with active components of CHMs overcome their disadvantages in physicochemical properties and their application
| Entrapped components | Disadvantages | Drug loading | Cancer model | Main results | Reference |
|---|---|---|---|---|---|
| β-Elemene | Phlebitis, fever, pain and induced bleeding are caused by solubilizing agents after intravenous injection | Ethanol injection method |
In vivo Kunming mice |
In vivo The size of PEGylated liposomes was 221.4 nm and the EE% was 92.7%. The AUC and half-life of PEGylated liposomes were both enhanced, being 1.5- and 6.0-fold larger than those of conventional β-elemene liposomes and free β-elemene, respectively. |
[389] |
| Brucine | The therapeutic amount of brucine is close to the toxic amount | Ethanol injection and ammonium sulphate gradient methods | \ | Different molecular weights of PEG were screened for their modification on the liposomes surface. The size of PEGylated liposomes was 120 nm with the EE% at 93.7%. The liposomes had a better sustained-released effect than free brucine and good stability in 4 °C. | [390] |
| Berberine | Hypotension and vasodilation, and a quick and wide distribution to major organs after solution injection | pH gradient-film dispersion method |
In vivo Balb/c nude mice xenografted gastric tumor (SGC-7901 cells) |
In vivo PEG-modified berberine liposomes significantly increased circulation retention compared to berberine solution and proved effective and safe in suppressing the 45.8 % tumor growth in nude mice. |
[377,391,392] |
| Oxymatrine | Short half-life (133 min) in human body after intramuscular injection | Thin-film dispersion, reversed-phase evaporation, pH gradient and ammonium-sulfate gradient methods | \ | Oxymatrine liposomes could be produced with EE% at 57.2% by ammonium-sulfate gradient method. The ammonium sulfate concentration, incubation time, and drug-to-lipid ratio greatly influenced the EE%, while the incubation temperature had almost no effect on EE%. | [393] |
| Oridonin | Low water solubility | Ethanol injection method followed by freeze-drying |
In vivo SD rats |
In vivo The levels of stealth liposomal oridonin in the blood were increased, with MRT about 2- and 6-fold longer than that of conventional liposomes and free oridonin solution, respectively. |
[394] |
| Artemisinin | Low water solubility | Ethanol injection method |
In vitro MCF-7 cells |
In vitro The cytotoxicity effect of pegylated liposomal artemisinin was greater (IC50=1.58 μg/mL) than that of liposomal artemisinin. |
[395] |
| Glycyrrhetinic acid (GA) | Low water solubility | Film-dispersion method |
In vivo SD rats |
GA-loaded PEGylated liposomes had a 2.75-fold larger AUC, a 1.7-fold longer MRT, and a 0.4-fold lower CL, compared to GA solution. | [396] |
| Oleanolic acid (OA) and Doxorubicin (DOX) | Low aqueous solubility and low permeability across the intestinal mucosa | Ethanol injection method |
In vivo Balb/c nude mice xenografted liver tumor (HepG2 cells) In vitro) HepG2 cells |
In vivo OA-loaded liposomes formulation inhibited tumor growth and OA had a protective effect to attenuate DOX toxicity.) In vivo) The IC50 value for codelivery of OA and DOX in liposomes is significantly lower than OA-loaded liposomes alone. |
[397] |
| Honokiol | Poor stability and water solubility | Ethanol injection method followed by freeze-drying |
In vivo BALB/c nude mice xenografted NSCLC tumor (HCC827 and H1975 cells) |
In vivo Liposomal honokiol showed antitumor activities in four xenografted models, including inoculating HCC827 (gefitinib-sensitive) and H1975 (gefitinib-resistant) cells. |
[398] |
| Plumbagin (PLB) | Severe side effects caused by solubilizing agents in injection | Film hydration method |
In vivo C57BL/6J mice bearing melanoma (B16F1) |
In vivo The long circulating liposomes exhibited a 36.4-fold increased plasma and significantly less CL in comparison to free PLB. The PEGylated liposomes significantly delayed tumor growth with median survival value at 27 days. |
[399] |
| Quercetin (Que) and Adriamycin (ADM) | Low aqueous solubility, low bioavailability, and instability during processing and storage | Film-ultrasound technique with ammonium sulfate gradient method |
In vivo BALB/c nude mice xenografted breast cancer (MCF-7/ADR) In vitro ADM-resistant cell strains (HL-6/ADR and MCF-7/ADR) |
In vivo Liposomes enveloping QUE and ADM extended the half-life and increased the blood concentration of ADM, with the highest inhibition rate of tumor growth. In vitro The combination of ADM and QUE can enhance cell toxicity to ADM-resistant cells, achieving 4.81- and 3.21-fold higher in HL-6/ADR and MCF-7/ADR, respectively. |
[400] |
| Crocin | Water solubility, and instability during processing and storage | Film-ultrasound technique with extrusion |
In vivo BALB/c mice xenografted colorectal cancer (CT26 cells) In vitro CT26 cells |
In vivo Liposomal crocin (50 and 100 mg/kg) significantly prolonged survival time compared with crocin and free doxorubicin, in a dose-dependent manner. In vitro PEGylated liposomes with higher cholesterol retained crocin more effectively and thus showed higher IC50 values in C26 cells compared to crocin alone. |
[401] |
| Silibinin and Glycyrrhizic acid | Poor solubility in water and oil and low bioavailability | Film hydration method with HEPES buffer and sonication |
In vitro HepG2 and fibroblast cell lines |
In vitro The IC50 for pegylated liposomal silibinin and glycyrrhizic acid was 10-times and 2.3-times lower than that of free silibinin and glycyrrhizic acid, in the HepG2 and fibroblast cells, respectively. |
[402] |
| Resveratrol (Res) and DOX | Low water solubility | Film hydration method |
In vitro NT8e cells |
In vitro The formulation exhibited a superior effect on the apoptosis proteins and cell cycle but had a higher IC50 value than that of free DOX. |
[403] |
| Celastrol | Highly hydrophobic nature | Film hydration method and extrusion |
In vitro Vertebral-cancer of the prostate (VCaP) cells |
In vitro The lipid composition influenced the EE%, serum stability and drug release of celastrol from PEGylated liposomes. |
[404] |
| Ursolic acid | Low water solubility | Film hydration method and homogenization |
In vivo Nude mice xenografted breast tumor (MCF-7 cells) |
In vivo Magnetic resonance parameters of tumor-bearing animals showed a possible antiangiogenic effect induced by ursolic acid-loaded liposomes |
[405] |
| Caffeic acid, Carvacrol, pterostilbene, Caffeic acid phenethyl ester (CAPE), Carvacrol, N-(3-oxo-dodecanoyl)-l-homoserine lactone (3-oxo-C12-HSL), Thymol, and Resveratrol | Poor water solubility or instability | Film hydration method |
In vivo Balb/c nude mice xenografted head and neck squamous-cell carcinoma (14C-tumor cells) |
In vivo These compounds were entrapped in liposomes with better stability. Liposomal 3-oxo-C12-HSL and resveratrol inhibited tumor growth significantly as compared to control group. |
[406] |
| Betulinic acid (BA) | Poor water solubility | Ethanol injection technique |
In vivo Kunming mice xenografted cervical cancer (U14 cells) In vitro HepG2 cells and HeLa cells |
In vivo The PEGylated BA-loaded liposomes with sustained release profile can effectively accumulate in tumor tissues. The tumor inhibitory rate of PEGylated BA was 1.2-fold stronger than that of BA liposomes. |
[407] |
Abbreviations: AUC, the area under the plasma concentration-time curve; MRT, mean residence time; NSCLC, non-small cell lung cancer; CL, clearance; IC50, half inhibit concentration