Table 2.
Delivery of alkaloids derived from traditional Chinese medicine by various liposomes.
| Liposome types | Alkaloids | Liposome composition | Preparation | Method of model | Method of dosing | Effects | References |
|---|---|---|---|---|---|---|---|
| Conventional liposomes | 10-HCPT | Lecithin: Chol; or EPC: Chol | Modified thin-film hydration method | Healthy rabbits | Iv. | The lactone: CL ↓ 52.6%, AUC0–∞ ↑ over one folds, Vd ↓ 50.5%; scar adhesion ↓ | (Shi et al., 2010b; Yang et al., 2011) |
| SN-38 | SPC:Chol (1:6) | Carrier-deposition method | New Zealand white adult rabbits | Iv. drip | AUC0–6 h of the liver ↑ 3.95-fold; AUC0–6 h of the spleen ↑ 6.7-fold; AUC0–6 h of the lung ↑ 4.7-fold; AUC0–6 h of the kidney ↓ 85.6%; AUC0–6 h of the heart ↓ 30.8% | (Li & Wang, 2016) | |
| DB-67 | DMPC: DMPG (7:3) or DSPC:m-PE G: DSPE (95:5) | – | SCID mice | Iv. | AUClactone of the spleen ↑ 1.07-fold; AUClactone of the lung ↑ 0.95-fold; t1/2 in PBS ↑ 5.66-fold | (Joguparthi et al., 2008; Zamboni et al., 2008) | |
| Vincristine | Sohingomyelin: Chol or HSPC: Chol: PEG5000-DSPE | The pH gradient method | Adults | Iv. | Therapeutic index ↑ ; target tumor ↑ ; individual dose ↑ over 2-fold; CL ↓ 40.4%; Cmax ↑ 52.3%, AUC ↑ 73.1%, MRT ↑ 56.6%, t1/2 ↑ 55.6% | (Thomas et al., 2009; Yan et al., 2012; O'Brien et al., 2013) | |
| Long-circulating liposomes | Ligustrazine | – | – | – | – | MRT ↑ , AUC ↑ , t1/2 ↑ , CL ↓ ; uptake of the drug by the phagocyte cells ↓ | (Yang et al., 2016) |
| Berberine | DPPC, DSPE-PEG2000, Chol (1: 0.08: 0.28); or HSPC: DSPC: DSPE-PEG2000 | Ethanol injection method or thin film hydration reverse phase evaporation method | Mice | Iv. | LVEF, FS ↓ ; EDV, ESV, HR ↓ ; t1/2 ↑ 5.13-fold, AST ↑ , ALT ↑ ; tumor weight ↓ 46.5% than the PBS; IC50 towards HepG2 cells ↓ 60.5% | (Lin et al., 2013; Allijn et al., 2017) | |
| Brucine | DSPE-PEG2000, Chol SPC/DPPC/HSPC/DSPC or SPC:HSPC:Chol:DSPE-mPEG | Ammonium sulfate gradient loading method | SD rats or Kun-Ming mice | Iv. | AUC0–∞ of the HSPC ↑ 4.7-fold than the SPC, CL/F of the HSPC ↓ 88.9% than the SPC; LD50 of the HSPC ↑ 37.2% than the SPC; The retention time of the mixture of HSPC and SPC ↑ 2.22-fold compared to the SPC; AUC of the mixture of HSPC and SPC in tumor ↑ 29.3% compared to the SPC | (Chen et al., 2012; Li et al., 2013) | |
| Vincristine | PEG-DSPE:HSPC:Chol (1:22:10) | The pH gradient method | SD rats | Iv. | t1/2 of PEG-DSPE formulation ↑ 0.4-fold compared to the market; 12 h of retardation in the clearance from blood | (Zhang et al., 2016) | |
| Targeted-release liposomes | Oxymatrine | Lecithin:Chol:RGD | – | SD rats | Iv. | MMP-2, TIMP-1 ↓ , type 1 procollagen ↓ , ALP ↓ | (Chai et al., 2012) |
| Berberine | EPC:Chol DQA-PEG2000-DSPE (57/38/4.35) | Film dispersion method | Female BALB/c nude mice | Iv. | Drug in MCF-7 cancer stem cells ↑ 0.73-fold; Caspase 3, 9 activity ↑ , Bax ↑ , Bcl-2 ↓ | (Ma et al., 2013) | |
| Matrine | HSPC:Chol:DSPE-mPEG2000:DSPE-PEG-MAL (2:1:0.1:0.01) | The pH-gradient method | – | – | Bcap-37, HT-29, A375 cells growth ↓ , apoptosis and anti-proliferation to cancer cells ↑ | (Liu et al., 2010) | |
| Vincristine | EPC:Chol:DSPE-PEG2000:TF:DSPE-PEG2000-NHS | Film dispersion method | SD rats | Iv. | t1/2α ↑ 0.93-fold , Vd ↓ 89.6% | (Song et al., 2017) | |
| Triggered-release liposomes | Berberine | Spc/P(NIPAM-co-MAA-co-ODA) | Lipid film hydration method | – | – | Thermo sensitivity | (Zhou et al., 2012) |
| Vincristine | EYPC:DSPE-PEG2000 (90:10 or DPPC:DSPE-PEG2000:MSPC (75:17:8) | Lipid film hydration method | Nude mice | Iv. | Anti-proliferation and apoptosis to Hela cells ↑ , tumor volume ↓ , temperature sensitivity | (Liu et al., 2015; Li et al., 2016) | |
| Others | Oxymatrine | SPC:PS:Chol:TO:TMC | Double emulsification method | Wistar rats | Orally | AUC ↑ 2.26-fold, Cmax ↑ 1.29- fold , Tmax ↑ 1.32-fold | (Cao et al., 2009) |
| Harmine | SPC:Chol:TMC (20:5:4) | Thin-film hydration method | SD rats | Ig. | AUC ↑ 1.26-fold than the free drug, AUC ↑ 0.53 fold than the normal liposome, bioavailability ↑ 0..52-fold than the normal liposome; degradation to cancer cells ↓ | (Chen et al., 2016) |
10-HCPT: 10-hydroxycamptothecin; Chol: cholesterol; EPC: egg phosphatidyl choline; Iv.: intravenously; CL: clearance; AUC: area under the concentration-time curve; Vd: the apparent volume of distribution; SN-38: 7-ethyl-10-hydroxy-camptothecin; SPC: phosphatidylcholine; DB-67: 7-silyl-modified camptothecin; DMPC: 1,2-dimyristoylsn-glycero-3-phosphocholine; DMPG: 1,2-dimyristoylsn-glycerol-3-phospho-sn-1-glyercol; DSPC: 1,2-distearoyl-3-sn-phosphatidylcholine; PEG: polyethylene glycol; DSPE: distearoylphosphatidylethanolamine; SCID mice: severe combined immunodeficient mice; t1/2: half-life; PBS: phosphate buffer saline; HSPC: hydrogenated soybean lecithin; Cmax: maximum plasma concentration; MRT: mean residence time; DPPC: dipalmitoyl phosphatidylcholine; LVEF: left ventricular ejection fraction; FS: fraction shortening; EDV: end diastolic volume; ESV: end systolic volume; HR: indicates heart rate; AST: glutamic oxaloacetic transaminase; ALT: glutamic pyruvic transaminase; IC50: the half maximal inhibitory concentration; HepG2 cells: human hepatoma cell lines; SD rats: male Sprague-Dawley rats; CL/F: apparent plasma clearance; LD50: the median lethal dose; RGD: Arg-Gly-Asp peptide; MMP-2: matrix metallopeptidase; TIMP-1: tissue inhibitor of metalloproteinase; ALP: alkaline phosphatase; DQA: dequlinium; MCF-7: Michigan Cancer Foundation-7 human breast cancer; Bax: pro-apoptotic protein; Bcl-2: anti-apoptotic protein; MAL: maleimide; A375: melanoma cell lines; Bcap-37: the breast cancer cell lines; HT-29: colon cancer cell lines; TF: transferrin; NHS: N-hydroxysuccinimidyl; P (NIPAM-co-MAA-co-ODA): Poly (Nisopropylacrylamide-co-methacrylic acid-co-octadecyl acrylate); EYPC: egg yolk lecithin; MSPC: 1-stearoyl-2-hydroxy-sn-glycero-3- phosphatidylcholine; PS: Phosphatidylserine; TO: Glycerol trioleate; TMC: N-trimethyl chitosan; Ig: intragastrically.