Table 2.
Polyplex systems to deliver mRNA
| Polymer component a) | Molecular weight | Preparation Method | Average size [nm] |
Zeta potential [mV] |
Cation to RNA ratio | Design elements | Experimental application | Outcome b) | Refs. |
|---|---|---|---|---|---|---|---|---|---|
| PEI | 25 kDa | Mixing in HBG (20 × 10‐3 m of HEPES, 5% glucose; pH 7.4) | 78–93 | 10–18 | N/P = 12 |
Fatty acids Disulfide linker |
Intratracheal | Local expression | [23a] |
| bPEI | 2 kDa | Mixing | 234 | 47.3 ± 3.6 | N/P = 16 | Cyclodextrin | I.m. vaccine | Local expression | [23b] |
| PEI | 1.8 kDa | Mixing in RNase‐free water | 145 | 64.2 ± 0.9 | N/P = 32 | Vitamin E succinate | I.m. vaccine | Local expression | [24b] |
| PEI | 25 kDa | Mixing | 118 ± 4 | Not reported | 4:1 w/w | Stearic acid | Subcutaneous | Antigen‐specific immune response | [25] |
| PEI | 2 kDa | Mixing | 75 ± 11 | 27.5 ± 3.7 | 3:1 w/w | Deoxycholic acid | Intracerebral | Reduced Ischemic stroke | [26] |
| PEI | 2 kDa | Mixing in RNase‐free water | 80 | 26 | N/P = 16 | Cyclodextrin | I.m. vaccine | Local expression | [29] |
| PEI + PEG | 22 kDa | Mixing | 60 | 10 | N/P = 8 | Amino group | i.v. | Delivery to lungs | [28] |
| pAsp | Not reported | Mixing in 10 × 10‐3 m HEPES (pH 7.3) | ≈110 | 15–5 | N/P = 5 | Cyclohexylethyl | i.v. | Lungs, Spleen | [38] |
| PLGA + chitosan | 4–15 kDa | Emulsion‐diffusion‐evaporation | 157 ± 1 | 30.8 ± 0.115 | 25:1 w/w | Chitosan | Intratracheal | Lungs | [43] |
| PLGA + chitosan | 4–15 kDa | Not reported | 142 ± 4 | 21.9 ± 2.7 | Not reported | Chitosan | Intratracheal and i.v. | Lungs | [44] |
| PBAE+PEG lipid | 2.2 kDa | Mixing in 25 × 10‐3 m NaOAc buffer | 164 | 14.6 ± 5.6 | Not reported | Caprolactone | i.v. | Spleen | [47] |
| PBAE+PEG lipid | 4–10 kDa | Mixing in 25 × 10‐3 m magnesium acetate buffer (MgAc2, pH 5) | 100 | 42 | 30:1 w/w | Hydrophobicity and amine groups | i.v. | Lungs, Liver | [48a] |
| PBAE+PEG lipid | 2.7 kDa | Mixing in acidic buffer (pH 5.3) | 187 ± 44 | 39.3 | N/P = 57 | Amine groups and PEG lipid | i.v. | Lungs, Liver | [48b] |
| PBAE+PGA | Not reported | Mixing in NaOAc buffer | 107 | 4 ± 2 | 60:1 w/w | Ab for targeting | i.v. | T cells | [49] |
| Hyperbranched PBAE | 20 kDa | Mixing | 160 | 45 | 50:1 w/w | Amine groups | Nebulized intratracheal | Lungs | [51] |
| Polyesters+surfactant | 4.2–7 kDa | Mixing in 10 × 10‐3 m citric acid/trisodium citrate buffer (pH 4.2) | 100 | −17–1 | 30:1 w/w |
Alkyl length Amine groups |
i.v. | Lungs, Spleen | [52] |
| PACE+PACE‐PEG | PEG: 5k Da | Mixing in 25 × 10‐3 m sodium acetate buffer (pH 6) | 200 | −22–‐3.1 | 100:1 w/w | PEG density optimized | i.v. | Lungs, Spleen | [53] |
| Chitosan | Not reported | Mixing in 4% acetic acid solution | 100 | Not reported | Not reported | Protein coating | Intranasal | Local expression | [57] |
| Protamine | Not reported | Not reported | Not reported | 1:2 w/w | Protamine MW | i.d. | Local expression | [60b] | |
| PAMAM+PEG lipid | Not reported | Microfluidic preparation | 120 | 5:1 w/w | Alkyl‐modified | I.m. vaccine | Local expression | [79] | |
| pABOL | 8 kDa | Titrating saRNA solutions into polymer solutions | ≈70 | + 23 | 45:1 w/w |
Bioreducible MW optimized |
I.m. vaccine | Local expression | [80] |
| p(BAC‐TETIm/AD), p(BAC‐TET‐Im/β‐CD)), PEG‐p(BAC‐TET‐Im/AD)–PEG | 8.5–19.5 kDa | Mixing in 25 × 10‐3 m NaOAc buffer (pH 5.5) | 168‐179 | −2.5–7.9 | Not reported | Redox‐responsive; Host–guest interaction between β‐CD and AD | Intracellular | HEK 293, RAW 264.7, HCT116, and NHDF cells | [91] |
a)
The full name of polymers can be found in the main text
b)
HEK293: human embryonic kidney 293 cell line; RAW 264.7: murine macrophage cell line; HCT116: human colorectal carcinoma cell line; NHDF: human dermal fibroblast cell line.