Table 1 A representative summary of the applications of IDDSs in gene delivery
From: Ionizable drug delivery systems for efficient and selective gene therapy
IDDSs | Vehicle | Composition | Payload | Advantage | Disadvantage | References |
|---|---|---|---|---|---|---|
Ionizable polymeric nanosystems | Chitosan-based polymeric nanoparticle complexes | Chitosan/DNA | pDNA | Low cytotoxicity, biodegradability, low immunogenicity, low cost and high positive charge density | Transfection efficiency depends on a range of formulation parameters | [35] |
Chitosan/PLGA | OMR | [36] | ||||
Chitosan/pGL3 | pGL3 | [37] | ||||
Chitosan/DNA | pDNA | [38] | ||||
Heparin/poly(amino acid)-based polymeric nanoparticle complexes | PDMAEMA/heparin | pDNA | They protect cationic polymers from interference by serum | Heparin itself cannot be used as a gene carrier | [39] | |
Poly-l-lysine/heparin | siRNA and pDNA | [40] | ||||
Polypeptide-based micelles/nanoparticles | Lipid/dendrimers | siRNA | Good biocompatibility and biodegradability. Amino acid residues can be infinitely combined and modified. Peptides have naturally encoded functions | The properties of peptide-based nanocarriers depend not only on peptides but also on lipids, polymers or inorganic components | [41] | |
(HR)3gT peptide | ssDNA and dsDNA | [42] | ||||
CR8GPLGVH5-Pal peptide | pDNA | [43] | ||||
Bis(h9)-K-K4 and bis(h5)-K-K4 peptide | pDNA | [44] | ||||
cRGD-hK peptide | pDNA | [45] | ||||
RALA peptide | siRNA | [46] | ||||
KHV-LHRH peptide | pDNA | [47] | ||||
Ionizable lipid-mediated drug delivery systems | Ionizable lipid nanoparticles | DODMA/eggPC/Ceramide-PEG | siRNA | Good biocompatibility, good biodegradability, low toxicity, low immunogenicity and structural flexibility. They are easy to manufacture on a large scale | They show some degree of instability in the blood | [33] |
Lipids with aminoglycoside tobramycin | mRNA, DNA and siRNA | [30] | ||||
KALA peptide and ssPalmE-LNP | mRNA | [32] | ||||
Ionizable lipid, Chol, DSPC and PEG-lipid | siRNA and mRNA | |||||
Ionizable liposomes | KC2, DSPC, Chol, and PEG-lipid | siRNA | They can increase the stability of the encapsulated drug. They enable transmembrane transport | They are prone to agglomeration, are unstable in storage, and have low drug loading | [50] | |
Ionizable lipidoid, CH, DOPE, and PEG-lipid | mRNA | [51] | ||||
DODAP, DOPE, DSPC, PEG-PE and Chol | siRNA | [52] | ||||
MDH, DSPE-PEG and Chol | siRNA | [53] | ||||
Ionizable polymer-lipid nanosystems | PEI-lipid NPs | C15 epoxide-terminated lipids and PEI | siRNA | They enable non-immunogenic gene transfer and are easy to manufacture and store. They acquire various modifiable functions | Their endosomal release and targeting capabilities require further optimization | [54] |
PBAE-lipid NPs | PBAE and mPEG-PE | mRNA | [55] | |||
APE-lipid NPs | APE, Chol, and mPEG-PE | mRNA | [56] | |||
PSS-lipid NPs | PSS, amine-containing lipidoid | siRNA and mRNA | [57] |