Table 3.
Delivery of alkaloids derived from traditional Chinese medicine by sustained-release delivery systems.
| Carrier types | Alkaloids | Carrier composition | Preparation | Method of model | Method of dosing | Effects | References |
|---|---|---|---|---|---|---|---|
| Polymeric nanoparticles | Ligustrazine | PLGA | Hot-melting extrusion | NZW rabbits | Iv. | Relatively stable drug concentration for about 21 days, ideal zero-order in-vitro drug release; obvious inhibition to PVR for at least 5 weeks with only a 12.5% occurrence | (Xu et al., 2010) |
| Aconitine | PLGA | O/W single-emulsion/solvent-evaporation technique | – | – | Stability of aconitine ↑ ; slow-release behavior for 12 h | (Zhang et al., 2015b) | |
| Vincristine | PEG-PLGA or PLGA-PEG-folate | W/O/W emulsion solvent evaporation method | SD rats | Iv. | The NPs: AUC0–16 h ↑ 2.39-fold, MRT ↑ 4.32-fold, the CL↓69.7%; cytotoxicity to MCF-7 cells ↑ , IC50 ↑ 2.91-fold | (Chen et al., 2011a,b) | |
| Berberine | PCL | Nanoprecipitation method | SD rats | Ip. | T50% of the NPs ↑ 46-fold; stable at 25 °C storage | (Vuddanda et al., 2015) | |
| Chitosan | Ionic cross-linking method | The NPs: AUC0–96 h) ↑ 0.15-fold, MRT0–96 h ↑ 2.41-fold, Tmax ↑ 5- fold, Cmax↓70%, t1/2α ↑ 4.08-fold, t1/2β ↑ 3.42-fold; anti-apoptosis activity to chondrocyte ↑ | (Zhou et al., 2015) | ||||
| Tetrandrine | PVP-b-PCL | Nanoprecipitation method | – | – | Apoptosis to A549 cells ↑ , Bcl-2 protein↓, Bcl-xL protein↓, A549 cells migration and invasion↓, MMP-2 and MMP-9↓, MMP-3 ↑ | (Xu et al., 2014) | |
| Sustained-release gel system | Vincristine | Dextran, chitosan, β-glycerophosphate | Emulsion polymerization method and cold method | Swiss albino male mice | Sc. | The gels: AUC0–∞ ↑ 10.3-fold, MRT ↑ 9.9-fold , t1/2 ↑ 0.6-fold, CL↓91.1%, Vd↓85.7% , IC50↓ | (Thakur et al., 2016) |
| PLGA, PEG, PNIPAAm | W/O/W emulsion technique | SD rats | Medium survival period ↑ in brain tumor site | (Ozeki et al., 2012) | |||
| Sinomenine | Carbopol 940, HPMC (1:4) | – | White New Zealand rabbits | Eye drop | The gels: AUC0–8 h ↑ 1.7-fold, t1/2 ↑ 0.24-fold, MRT0–8 h ↑ 0.23-fold | (Song et al., 2013) | |
| Tetrandrine | Calcium alginate gel bead | – | Healthy dogs | Orally | The gels: Tmax ↑ 1.27-fold, t1/2 ↑ 0.58-fold, Cmax↓24.4% , 12 h of sustained release in vitro | (Ma et al., 2009) | |
| Emulsion | Ligustrazine | Soybean oil, oleic acid, lecithin, poloxamer 188, glycerol (240:12:20:12:45) | – | SD rats | Iv. | The emulsions: AUC0–10 h ↑ 0.61-fold, MRT ↑ 0.77-fold, t1/2 ↑ 0.76-fold, CL ↓ 40%; AUC0–3 h of the liver ↑ 10%, AUC0–3 h of the kidney ↑ 18%, AUC0–3 h of the brain ↑ 29% | (Wei et al., 2012) |
| Vincristine | Soybean lecithin, Solutol HS15, soybean oil (1:1:8) | Classical high-pressure homogenization | Wistar rats | Iv. | The emulsions: AUC0–∞ ↑ 0.46-fold, MRT0–∞ ↑ 0.22-fold, t1/2 ↑ 0.43-fold, Cmax ↑ 1.16-fold; cytotoxicity to MCF-7 cells ↑ | (Zhang et al., 2013) | |
| Others | Tetrandrine | Phospholipids, Solutol HS15, NaCl, and distilled water | Phase inversion method | SD rats | Oral gavage | The nanocapsules: AUC0–24 h ↑ 1.08-fold, MRT0–24 h ↑ 0.1-fold, Tmax ↑ 1.56-fold | (Zhao et al., 2013) |
| Sinomenine | Chitosan, gelatin, and alginate | Layer-by-layer technique | – | – | Light stability ↑ ; release rate↓ as the increase of chitosan/alginate bilayer number | (Shi et al., 2010a) | |
| Vincristine | Silk fibroin fibers | – | Female NCr nude mice | Iv. | Tumor growth↓ | (Harris et al., 2016) |
PLGA: dl-lactide-co-glycolide; Iv.: intravenously; NZW: New Zealand white; PVR: proliferative vitreoretinopathy; O/W: oil in water; PEG: poly (ethylene glycol); Folate: folic acid; W/O/W: water–oil–water; SD rats: male Sprague–Dawley rats; NPs: nanoparticles; AUC: area under the concentration-time curve; MRT: mean residence time; CL: clearance; MCF-7 cells: Michigan Cancer Foundation-7 human breast cancer cells; IC50: concentration of drug required to kill 50% of the cells; PCL: poly(ε-caprolactone); Ip.: intraperitoneally; T50%: the time required for 50% drug release; Cmax: maximum plasma concentration; Tmax: time to reach Cmax; t1/2α: distribution half-life; t1/2β: elimination half-life; PVP-b-PCL: poly (N-vinylpyrrolidone)-block-PCL; A549 cells: the non-small cell lung cancer cell; Bcl-2 and Bcl-xL: anti-apoptotic proteins; MMP-2 and MMP-9: matrix metalloproteinases; MMP-3: tissue inhibitor; Sc.: subcutaneous route of administration; Vd: apparent distribution volume; PNIPAAm: poly-N-isopropylacrylamide; HPMC: hydroxy propyl methyl cellulose; T1/2: elimination half-life; NaCl: sodium chloride.