. 2022 Aug 8;10:963004. doi: 10.3389/fchem.2022.963004

TABLE 1.

Liposomal natural products and their derivatives.

Drug	Source	Lipid composition	Size/nm	Bioactivity	Ref
Artemisinin	Artemisia annua L	Free	N.A.	C _max: 0.25 ± 0.08 μM; AUG_0–24h: 0.132; t _1/2β: 0.38 h; CL: 63.11 ml/h	Isacchi et al. (2011a)
		P90G, CHOL	136.2 ± 42.27	C _max: 1.11 ± 5.60 μM; AUG_0–24h: 0.836; t _1/2β: 0.67 h; CL: 9.97 ml/h
		PEG2000, P90G, CHOL	132.6 ± 8.78	C _max: 1.04 ± 0.01 μM; AUG_0–24 h: 0.899; t _1/2β: 2.02 h; CL: 9.20 ml/h
		L-α-phosphatidylcholine, CHOL	79 ± 5	IC₅₀: 6.0 ± 1.4 μg/ml for intracellular Leishmania donovani amastigotes; IC₅₀: 5.1 ± 0.9 μg/ml for infected macrophages	Y. Want et al. (2017)
ADP109	Artemisinin	Free	N.A.	IC₅₀: 0.07 ± 0.01 μM to BT474 cells; IC₅₀: 10 ± 3 μM to MDA-MB231 cells	Zhang et al. (2013a)
ADP109	Artemisinin	EPC	70 ± 20	IC₅₀: 0.08 ± 0.01 μM to BT474 cells; IC₅₀: 7 ± 2 μM to MDA-MB231 cells	Zhang et al. (2013a)
AMPm109	Artemisinin	Free	N.A.	IC₅₀: 1.3 ± 0.8 μM to BT474 cells; IC₅₀: >> 100 μM to MDA-MB231 cells	Zhang et al. (2013a)
AMPm109	Artemisinin	EPC	50 ± 20	IC₅₀: 1.3 ± 0.4 μM to BT474 cells; IC₅₀: >> 20 μM to MDA-MB231 cells	Zhang et al. (2013a)
Baicalin	Scutellaria Scutellaria baicalensis Georgi	HSPC, CHOL, F-PEG-CHEMS	68.4 ± 3.6	IC₅₀: 58.3 ± 3.3 μg/ml to HeLa Cells	Chen et al. (2016)
		HSPC, CHOL, PEG-CHEMS	70.9 ± 1.4	IC₅₀: 76.1 ± 4.6 μg/ml to HeLa Cells
		HSPC, CHOL	87.6 ± 1.6	IC₅₀: 78.8 ± 4.2 μg/ml to HeLa Cells
		Free	N.A.	IC₅₀: 64.6 ± 3.8 μg/ml to HeLa Cells
BDMC	Turmeric	D-α-tocopherol polyethylene glycol 1000 succinate (TPGS or vitamin E TPGS), CHOL, mixlecithin	75.98 ± 5.46	Effective analgesic activity due to prolonged latency time, and the significantly decreased level of uric acid	Wang et al. (2021)
Betulinic acid	White birch	Egg phosphatidylcholine, egg phosphatidylglycerol	1000–1500	Efficiently inhibited human colon and lung tumors in nude mice	Mullauer et al. (2011)
Borneol	Dryobalanops aromatica Gaertn f., Blumea balsamifera DC	Phospholipid, CHOL	167.1	BO upregulates drug effect and synergistically help the BA to promote the recovery of the brain by inhibiting neuronal cell damage and apoptosis	Zhang et al. (2020)
Breviscapine	Erigeron breviscapus	HSPC: CHOL, Pluronic P85	118.8 ± 4.9	Significantly increased absorption in Caco-2 cells and oral bioavailability in rats	Zhou et al. (2014)
		PC, PG, CHOL, triolein or tricaprylin	17,900	bre-MVL significantly prolonged the retention both in vitro and in vivo compared with those of bre-TL.	Zhong et al. (2005)
		PC, CHOL	540		Zhong et al. (2005)
BP	Angelica sinensis	LPPC	200–280	Liposomal BP showed higher cytotoxicity to B16/F10 melanoma cells than free BP by arresting cell cycle at G0/G1 phase	Gao et al. (2018)
Camptothecin (CPT)	Oriental tree, amptotheca acuminata	Single/two/three components of EPC, DOTAP, DPPG, DLPC, DMPG, DOPC, DOPE, DMPE-DTPA, DPPC, DMPC, CHOL	30–35	Liposomal CPT improved the circulated time in mouse, compared with free CPT.	Flaten et al. (2013)
Chlorophyll	Chimonanthus salicifolius	Soybean lecithin, CHOL	21.7 ± 6.0	Significantly improved the water solubility of lipophilic chlorophyll and its NIR fluorescence	Chu et al. (2012)
Curcumin	Turmeric	Free	N.A.	EC₅₀: 1.9 and 1.5 μM to colon and lung cancer cells, respectively	Feng et al. (2017)
		EggPC, CHOL, DSPE-PEG	∼420	EC₅₀: 0.96 and 0.90 μM to colon and lung cancer cells, respectively
		EggPC, CHOL, DSPE-PEG (βCD-C)	∼420	EC₅₀: 3.25 and 2.9 μM to colon and lung cancer cells, respectively
Curcumol	Rhizoma zedoariae	Yolk lecithin, CHOL	<200 nm	Gal-s modified liposome enhanced the targeted delivery and treatment to liver cancer cells	Li et al. (2018a)
Daunorubicin	Streptomyces peucetius	DSPC, CHOL	45	Improved plasma half life and uptake by tumor	O'Byrne et al. (2002)
Docetaxel	Glycyrrhiza glabra L. (licorice)	Soybean phospholipids, CHOL	∼90 nm	GA-modified liposomes enhanced hepatocytes-target cellular uptake by receptor-mediated endocytosis	Li et al. (2012a)
Doxorubicin	Streptomyces peucetius	HSPC, CHOL, MPEG-DSPE	<100	AIDS-related Kaposi’s sarcoma; ovarian cancer resistant to paclitaxel and platinum	Waterhouse et al. (2001)
EPS	Epimedium	Soybean phospholipid, CHOL, tocopherol	200	The liposomal EPS significantly improved the immune response to Newcastle disease vaccine	Gao et al. (2012)
Ganoderic acid	Lucid ganoderma	P90G	150–180	Liposomal ganoderic acid has shown better antitumor effects by inhibiting various signaling pathways	Rahman et al. (2019)
Ginsenoside	ginseng	EYPC, CHOL	60.54 ± 1.78	The three ginsenoside-modifications enhanced the cellular uptake mediated by GLUT carriers	Hong et al. (2019)
			52.02 ± 1.42
			99.02 ± 2.55
Hirudin	Hirudo spp	DSPC, BC	191.49 ± 3.67	Inhibited the expression of VEGF and TGF-β1 in the rat kidneys	Wang et al. (2019)
Honokiol	Magnolia species	PC, cholesterol, PEG4000	130 ± 20	Liposomal honokiol significantly suppressed Lewis lung carcinoma overexpressing VEGF-D by inhibiting the tumor-associated lymphangiogenesis and metastasis	Wen et al. (2009)
Idarubicin	—	DSPC, DSPE-PEG2000	100 ± 30	Enhanced the circulation longevity of idarubicin to improve antitumor activity	Dos Santos et al. (2005)
Juglone	Juglans mandshurica	DPPC, CHOL	187 ± 12	The temperature-sensitive liposomes significantly inhibited HepG2 cell growth and proliferation upon exposed to hyperthermia	Zhao et al. (2016)
Juglone	Juglans mandshurica	DPPC, CHOL	220 ± 32		Zhao et al. (2016)
LBP	L. barbarum	Soybean phospholipids, CHOL	121.5 ± 0.2	The LBPL-OVA vaccine formulation enhanced immune responses	Bo et al. (2017)
LBP	L. barbarum	Soybean phospholipids, CHOL	121.13 ± 0.37	The LBPL-OVA vaccine formulation enhanced immune responses	Bo et al. (2017)
Matrine	Sophora flavescens	HSPC, CHOL, DSPE-mPEG2000, DSPE-PEG-MAL, cRGD-SH	97.59 ± 1.93	RGD-M-LCL significantly improved the tumor-specificity and suppressed the proliferation of Bcap-37, HT-29 and A375 cells, compared with matrine alone	Liu et al. (2010)
Morphine	Papaver somniferum	HSPC, mPEG-DSPE, CHOL	120.45 ± 10.53	Prolong analgesic effect and reduce drug addiction	Gómez-Murcia et al. (2019)
OP	Ophiopogonis japonicus	Soybean phospholipid, CHOL	245.3	Liposomes significantly improved the immune-enhancing activity of OP on Kupffer cells	Fan et al. (2014)
		Soybean phospholipid, CHOL	245.3	Liposomes significantly improved the immune-enhancing activity of OP against Newcastle disease virus on chicken	Fan et al. (2015)
		Soybean phospholipid, CHOL	245.3	Liposomal OP significantly activated mouse peritoneal macrophages	Sun et al. (2016)
		Soybean phospholipid, CHOL	245.3	Liposomal OP significantly enhanced the antioxidative and immunoregulatory activities of OP in ICR mice	Fan et al. (2016)
Paclitaxel	Taxus chinensis	Free	N.A.	IC₅₀: 42.38 ± 2.4 and 14.71 ± 1.37 nmol/L to SKOV-3 cells and HUVECs, respectively	Fu et al. (2019a)
		DPPC, DSPG, MPPC, DSPE-PEG	80.2 ± 3.9	IC₅₀: 31.19 ± 2.02 and 11.51 ± 1.13 nmol/L to SKOV-3 cells and HUVECs, respectively
		DPPC, DSPG, MPPC, DSPE-PEG, DSPE-PEG-K237	88.3 ± 4.7	IC₅₀: 13.61 ± 1.81 and 5.54 ± 0.95 nmol/L to SKOV-3 cells and HUVECs, respectively
		DSPE-PEG2000-Tn, DPPC	74 ± 0.36	IC₅₀: 1.93 nM to HepG-2 cells	Li et al. (2021a)
Parthenolide	Tanacetum parthenium	SPC	118.6 ± 0.2	PTL-Lips enhanced the antitumor efficacy	Gao et al. (2020a)
PPa	Terrestrial and marine plants, insect fluid	DPPC, CHOL, DSPE-mPEG_5k	100	Significantly improved the water solubility, prolong blood circulation and the bio-distribution in mice	Zhou et al. (2019)
PpIX	Living cells	PC	124 ± 0.85	IC₅₀: 0.53 ± 0.19 µM to Hela cells	Przybylo et al. (2016)
RGP	R. glutinosa	Soybean phospholipid, CHOL, Tween-80	170.83 ± 2.08	The positive modulation effects on dendritic cells	Huang et al. (2016)
RGP	R. glutinosa	Soybean phospholipid, CHOL, Tween-80	193.57 ± 1.89	The positive modulation effects on dendritic cells	Huang et al. (2016)
Resveratrol	Polygonum cuspidatum decoction pieces	Soybean lecithin, CHOL	146–585	Liposomal resveratrol showed neuroprotective effects on mitochondria in substantia nigra cells of Parkinsonized rats	Chen et al. (2021)
Sal B	Salvia miltiorrhiza Bge	PEG2000(18:0/18:0), P90G, CHOL	140.0 ± 6.5	The PEGylated liposome improved the antihyperalgesic effect by prolonged time	Isacchi et al. (2011b)
Topotecan	Synthetic analog of camptothecin	Sphingomyelin, CHOL	100 ± 20	The formulation enhanced the half-life in plasma	Chernov et al. (2017)
Triptolide	Tripterygium wilfordii	TRX-20, HSPC, PEG5000-PE	117.9 ± 1.4	Significantly improved the anti-inflammatory effects in membranous nephropathic model	Yuan et al. (2017)
Vincristine	Catha-ranthus roseus	DSPC, CHOL	100	Prolonged retention time dramatically improved the therapeutic effects on mice bearing P388 murine leukemia	Boman et al. (1994)
Wogonin	Scutellaria baicalensis Georgi	Free	NA	IC₅₀: 16.248 mg ml⁻¹ to HepG2 cells	Tian et al. (2014)
		Soybean phospholipids, CHOL	87.4 ± 4.8	IC₅₀: 3.344 mg ml⁻¹ to HepG2 cells
		Soybean phospholipids, CHOL, 18-GA-Suc	90.5 ± 2.2	IC₅₀: 2.292 mg ml⁻¹ to HepG2 cells