TABLE 2.
The summary of literature reviews for UA-loaded nanoparticles.
| No | Code | Carrier type | Formula-tion | Type of research | Information research | Administra-tion route | Reference |
|---|---|---|---|---|---|---|---|
| 1 | Lipo A | Liposomes | Not Available | Phase I Clinical Trials | Safety Evaluation of Double Dose and Antitumor Activity of Ursolic Acid (UAL) Liposomes in Subjects with Advanced Solid Tumors including: Non-Hodgkin Lymphoma (24%), Hodgkin Lymphoma (24%), Renal Carcinoma (5%), Hepatocellular Carcinoma (5%), Breast Cancer (9%), Lung Cancer (9%), Other Cancers (19%) | Intravenous 4 h infusion at doses equivalent to 54, 74, and 96 mg UA/m2 for 14 consecutive days | Qian et al. (2015) |
| 2 | Lipo B | Liposomes | Not Available | Phase I Clinical Trials | Toxicity evaluation of a single dose of intravenous ursolic acid liposomes (UAL) in healthy adult volunteers and patients with advanced solid tumors including Non-Hodgkin Lymphoma, Hodgkin Lymphoma, Renal Carcinoma, and Hepatocellular Carcinoma | Intravenous (IV) route at doses equivalent to 11, 22, 37, 56, 74, and 96, and 130 mg UA/m2 administered as a 4 h infusion | Wang et al. (2013) |
| 3 | Lipo C | Liposomes | Not Available | Phase I Clinical Trials | Toxicity evaluation of Ursolic Acid Nanoliposome (UANL) in healthy volunteers and patients with advanced solid tumors including: Non-Hodgkin Lymphoma (50%), Hodgkin Lymphoma (12.5%), Gut Cancer (12.5%), Hepatocellular Carcinoma (25%) | Intravenous (IV) route at doses equivalent to 74 mg/m2 as a single dose, 98 mg/m2, and 74 mg/m2 as double doses daily for 14 days via a 4 h infusion | Zhu et al. (2013) |
| 4 | Lipo D | Liposomes | Hydrophobic components (PC, Chl, and UA) at a weight ratio of 2:1:0.5; ethanol injection method | Preclinical or in vivo study | Tumor inhibition activity and toxicity studies of UA-PLL-HA in SCC-7 tumor-induced mice | Intravenous (IV) at a dose of equivalent to 20 mg UA/Kg mouse for 5 times every 4 days | Poudel et al. (2020) |
| 5 | Lipo E | Liposomes | PEGylated UA Liposomes composed of SPC, CHOL, and UA at a weight ratio of 50:8:5, respectively; ethanol injection method | Preclinical or in vivo study | Tumor growth inhibition study and cytotoxicity of UA PEGylated liposomes in mice with U14 cervical carcinoma cells | Intragastric route at a dose of equivalent to 80 mg UA/kg mouse twice a day for a total of 14 days | Wang et al. (2016) |
| 6 | Lipo F | Liposomes | Liposomes composed of hydrophobic components (SPC, CHOL and UA) at a weight ratio of 0:6:5; ethanol injection method | Preclinical or in vivo study | Tumor growth inhibition and toxicity studies of CS-UA-L in mice with U14 cervical carcinoma cells | Intragastric route at a dose of equivalent to 80 mg UA/Kg mouse once a day for 14 days | Wang et al. (2017) |
| 7 | Lipo G | Liposomes | Lipids-UA (HSPC/Kolesterol/DSPE-PEG2000/UA = 90/0/5/5 and 90/0/5/10, (molar ratio); thin film hydration method | Preclinical or in vivo study | Tumor and growth inhibition study of UA-L in mice with 4T1 tumors (breast cancer) | Intravenous (IV) route at a dose of equivalent to 10 mg UA/kg mouse for 5 times every other day | Zhang et al. (2020) |
| 8 | Lipo H | Liposomes | Lipid components of FA-UA-L: DOTAP/CHOL/MPEG-DSPE2000/FA-PEG-CHEMS at a molar ratio of 40:55:4, 5:0, 5 (equal to weight ratio of 28; 21,3; 12,6, dan 2, 1 mg). The ratio of UA to lipid is 1:20 (w/w); thin film hydration method | Preclinical or in vivo study | Tumor growth inhibition and toxicity studies of FA-UA/siRNA-L in mice with human kB cells tumor | Intravenous (IV) injection with the dose of 4.5 mg/kg for UA and 170 μg/kg for siRNA for 5 times every other day | Li et al. (2019) |
| 9 | Lipo I | Liposomes | Lipid composition: HSPC/CHOL/mPEG-DSPE2000/FA-PEG-CHEMS at molar ratio 63:32:4.5:0.5 (equal to weights amount of 48, 12, 13.4, and 5 mg), respectively. The ratio of UA to lipids is 1:20 (w/w); thin film hydration method | Preclinical or in vivo study | Efficacy study of FTL-UA for tumor inhbition in mice with human KB tumor cells | Intravenous (IV) at a dose of equivalent to 4.5 mg UA/kg mouse for 5 times every other day, which is similar to 23 mg/kg or 98 mg/m2 drug administration | Yang et al. (2014) |
| 10 | Nano A | Nanospheres | Not available | Preclinical or in vivo study | Tumor growth inhibition and toxicity studies of HCPT @F-Pt-PU NPs in mice with H22 subcutaneous tumors (liver cancer) | Intravenous (IV) injection at a dose of equivalent to 10 mg UA/kg mouse for 5 times every 2 days | Liu et al. (2021) |
| 11 | Nano B | Nanospheres | NP composed of 32 mg chitosan, 10 mg UA, 30 mg EDC, and 8 mg NHS. The ratio of UA to lipids is 1:10 (w/w); overnight magnetic stirring method | Preclinical or in vivo study | Tumor inhibition study of CH-UA-NPs in mice with H22 subcutaneous tumors (liver cancer) | Oral administration at a dose of equivalent to 11 mg UA/Kg mouse once every 2 days for a total of 8 times | Jin et al. (2016a) |
| 12 | Nano C | Nanospheres | NP composed of 32 mg chitosan, 10 mg UA, 30 mg EDC, and 8 mg NHS. The ratio of UA to lipids is 1:10 (w/w); overnight magnetic stirring method | Preclinical or in vivo study | FA-CS-UA-NPs tumor inhibiting activity study in MCF-7 xenograft bearing models (breast cancer) | Intraperitoneal (IP) injection at a dose of equivalent to 12.5 mg UA/kg mouse once a day for 9 times | Jin et al. (2016b) |
| 13 | Nano D | Nanospheres | Not available | Preclinical or in vivo study | Tumor growth inhibition efficacy and toxicity studies of UA-LA-ICG NPs in tumor bearing mice by murine H22-hepatocarcinoma cells induced tumor xenograft models | Intravenous (IV) injection at a dose of 10 mg/kg of UA and 2.5 mg/kg of ICG with 5 min irradiation at 24 h post injection | Zhao et al. (2018) |
| 14 | Nano E | Nanospheres | Prepared by making 3 mg UA solution in ethanol (1 ml, 6,569 mM) in 10 ml of water. The ratio of UA and NPs was 1:10, respectively; solvent exchange preparation method | Preclinical or in vivo study | Tumor inhibition efficacy and toxicity studies of UA NPs in mice bearing A549 xenograft models (lung cancer) | Intravenous (IV) injection at a dose of 8 mg/kg of UA for 21 days | Fan et al. (2018) |
| 15 | Nano F | Nanospheres | Not available | Preclinical or in vivo study | Tumor inhibiting activity and toxicity studies of UA NPs in H22-induced mice (Hepatocellular carcinoma) | Intraperitoneal (IP) injection at a daily dose of 50 mg/kg of UA for 10 days | Zhang et al. (2015) |
| 16 | Nano G | Nanospheres | Self-assembly method of polymer deposition | Preclinical or in vivo study | Antitumor activity and toxicity studies of Pec-8PUH NPs in mice with 4T1 tumors (breast cancer) | Intravenous (IV) injection at a dose of 10 mg/kg of UA once every 2 days for 5 times | Liu et al. (2018) |
| 17 | Poli A | Polymeric Micelles | PM composed of UA (4 mg) and mPEG2000-PLA2000 (40 mg) at a weight ratio of 1:10; thin film dispersion method | Preclinical or in vivo study | Antitumor activity and toxicity studies of UA-PMs in H22-induced mice (Hepatocellular carcinoma) | Intraperitoneal (IP) injection at a dose of 50 mg/kg of UA every 2 days for 6 times | Zhou et al. (2019) |
| 18 | Poli B | Polymeric Micelles | Solvent evaporation method | Preclinical or in vivo study | Antitumor activity and toxicity studies of U-SS-M in tumor bearing MG-63/Osteosarcoma (OS) | Intravenous (IV) injection at a dose of 11 mg/kg of UA every 3 days for 5 times | Fu et al. (2021) |
Notes: UAL, Ursolic Acid Liposome; UANL, Ursolic Acid Nanoliposome; UA-PLL-HA, Ursolic Acid-Poly-L-Lysine-Hyaluronic Acid; UA-PEGylated, Ursolic Acid-Polietilenglikolisasi; CH-UA-NPs, Chitosan-Ursolic Acid-Nanoparticles; CS-UA-L, Chitosan- Ursolic Acid-Liposome; CHOL/Chl, Cholesterol; DSPE-PEG2000, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N [methoxy (poly- ethylene glycol) -2000]; DOTAP, 1, 2-dioleoyl-3-trimethylammonium-propane; EDC, Ethyl-(3-3-dimethylaminopropyl) carbondiimide hydrochloride; FA-CS-UA-NPs, Folate- Chitosan-Ursolic Acid-Nanoparticles; FA-PEG-CHEMS, Folate Polyethylene Glycol Cholesteryl hemisuccinate; FA-UA/siRNA-L, Folate- Ursolic Acid/Small Interfering RNA-Liposome; F-Pt-PU, Folic Acid-Pectin-Eight-Arm PEG-UA conjugate; FTL-UA, Folate Receptor Targeted Liposome-Ursolic Acid; HCPT @F-Pt-PU NPs, Hydroxycamptothecin @folic acid-pectin-eight-arm PEG-UA nanoparticle; HSPC, Hydrogenated Soybean Phosphatidyl Choline; mPEG2000-PLA2000, Monomethoxy Polyethylene Glycol 2000 Poly Lactic Acid 2000; MPEG-DSPE2000, Monomethoxy Polyethylene Glycol 2000-Distearoyl Phosphatidylethanolamine; NHS, N-Hydroxy-Succinimide; PC, Phosphatidylcholine; Pec-8PUH NPs, pectin-eight-arm polyethylene glycol-ursolic acid/hydrooxycampothecin nanoparticle; SPC, Soybean Phosphatidyl Choline; UA-NPs, Ursolic Acid- Nanoparticles; UA-LA-ICG NPs, Ursolic Acid- Lactobionic Acid -Indocyanine Green; UA-PMs, Ursolic Acid-Polymer Micelles; U-SS-M, Micelles assembled by PEG-SS-UA (polyethylene glycol using a disulfide bond)