Table 2.
Overview of the proposed uptake mechanisms of different polymeric micelles.
| Material 1,2 | Uptake Mechanism(s) 1 | Cell type 3 | Drug 1 | Comments | Ref. |
|---|---|---|---|---|---|
| Mixed micelles: TPGS2K, HS15, F127 |
Energy dependent CME CvME |
Caco-2 | Curcumin DOX |
Only analyzed uptake of drug | [93] |
| OCC | CME CvME |
Caco-2 | Silybin Rhodamine-123 |
Only analyzed uptake of drug | [94,95] |
| OGC SH-OGC |
CME CvME |
Caco-2 | Paclitaxel Rhodamine-123 |
Only analyzed uptake of drug | [96,97] |
| P(PEGMEMA)75u-b-PMMA80u | Clathrin and caveolae independent CME CvME |
WiDr | DOX NileRed |
80% of the uptake was via a different, undefined uptake mechanism | [106] |
| PEG2000-b-PLGA5000 | Energy dependent CME |
Calu-3 NCI-H441 |
NileRed Curcumin acetate |
Only analyzed uptake of drug | [98,99] |
| PEG3000/2000/5000-PLA40000 PEG2000/5000-PLGA40000 |
Energy dependent Lipid raft mediated |
Caco-2 | Curcumin Coumarin 6 |
Only analyzed uptake of drug | [100] |
| PEG5000-b-PLA5000 | Direct drug transfer to cell membrane Energy dependent Caveolae/lipid raft-mediated endocytosis |
A2780 | Paclitaxel NileRed FRET, DAF/NileRed |
[5,107] | |
| PEG-b-PLGA | CvME | MCF-7 | DTX, 3-MA, CQ Coumarin 6 |
Only analyzed uptake of drug | [6] |
| PEO2000/5000/13000-b-PCL5000 PEO5000-b-PCL13000/24000 |
CME | MCF-7 | DiIC | PEO5000-b-PCL13000 showed fastest uptake, only analyzed drug uptake | [101] |
| PEO2000-b-PCL2600/2800 PEO5000-b-PCL4000 |
Direct drug transfer to cell membrane | HCT-116 | Pheo Conjugated Fluorescein |
[108] | |
| PEO45u-b-PCL23u | Energy dependent CME |
P19 | Conjugated Rhodamine | [3,109] | |
| PEO44u-b-PCL20u | Temperature, pH and energy dependent | PC12 | DiIC | Only analyzed uptake of drug | [110] |
| PEO5000-b-PCL2000 PEO5000-b-PDLLA5000 |
Direct drug transfer to cell membrane | KB | DiIC/DiOC Conjugated Fluorescein |
[49] | |
| PEO5000-b-PCL4000 | Direct drug transfer to cell membrane | MCF-7 | Pheo DiIC/DiOC |
Micelle uptake is slow (>4 hr), while release of drug is fast | [111] |
| PEOz6000-b-PLA1100/2200/3900/8500/10000/13700 PEOz2600/3300/4500/5600/6700/8900-b-PLA4000 | Energy dependent Cholesterol dependent Caveolae/lipid raft-mediated endocytosis |
MCF-7 | Paclitaxel Conjugated DEC |
PEOz/PLA ratio of 1.7-2.0 for optimal uptake | [17] |
| Val-TPGS Phe-TPGS |
Energy dependent CvME CME Macropinocytosis |
Caco-2 | Curcumin Coumarin 6 |
Enhanced transport across intestinal epithelial barrier, Only analyzed uptake of drug | [47] |
1 Abbreviations: N-octyl-O, N-carboxymethyl chitosan (OCC), N-mercapto acetyl-N′-octyl-O, N″-glycol chitosan (OGC), poly(poly(ethylene glycol) methyl ether methacrylate)(P(PEGMEMA)), poly(methyl methacrylate) (PMMA), Poly(ethylene glycol)/poly(ethylene oxide) (PEG/PEO), poly(lactide-co-glycolide) (PLGA), poly(lactide) (PLA), poly(ε-caprolactone) (PCL), poly((D,L-lactide) (PDLLA), poly(2-ethyl-2-oxazoline) (PEOz), D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), Clathrin-mediated endocytosis (CME), Caveolae-mediated endocytosis (CvME), Doxorubicin (DOX), 5-dodecanoylaminofluorescein (DAF), Docetaxel (DTX), 3-methyladenine (3-MA), Chloroquine (CQ), 1,1′-Dioctadecyl-3,3,3′,3′-Tetramethylindocarbocyanine Perchlorate (DiIC), Pheophorbide-a (Pheo), 3,3′-Dihexyloxacarbocyanine Iodide (DiOC), 7-N,N-diethylamino-coumarin-3 (DEC). 2 When available, the average molecular weight of the polymer block is listed (Dalton). If the number of monomeric units was provided, it is denoted by a number followed by ‘u.’ If different sizes of the same polymer were used, they are listed separated by ‘/.’ 3 Information on the various cell lines: human colon cancer cell lines (Caco-2 and WiDr, HCT-116), human lung cancer cell lines (Calu-3 and NCI-H441), human ovarian cancer cell line (A2780), human breast cancer cell line (MCF-7), mouse pluripotent embryonic carcinoma cell line (P19), pheochromocytoma rat cell line (PC12), HeLa contaminant human tumor cell line (KB).