Self-Assembled Hydrogel Nanoparticles for Drug Delivery Applications
Abstract
:1. Introduction
2. Materials, Properties, Methods
2.1. Materials
2.2. Properties
2.3. Methods
3. Drug Loading, Targeting and Release
3.1. Drug loading
3.2. Targeting
3.3. Drug release
4. Applications
4.1. Small molecular weight drug delivery
Polymer | Ligand | Target | Cell line | Drug binding | Stimuli | Ref |
---|---|---|---|---|---|---|
azo-dextran | aspirin | -- | COS-1 | simple mixing and irradiation with UV light | UV–vis light | [46] |
carboxymethyl chitosan-linoleic acid | adryamycin (anti-cancer) | -- | HeLa | direct dissolution | -- | [47] |
pullulan acetate | adriamycin (anti-cancer) | vitamin H (biotin) | HepG2 | dialysis method | -- | [48] |
pullulan acetate/sulfonamide | adriamycin (anti-cancer) | -- | MCF-7 | dialysis method | pH | [49] |
poly[(maleilated dextran)-graft-(N-isopropylacrylamide)] | camptothecin (anti-cancer) | -- | L929 | dialysis method | pH, temperature | [50] |
poly(N-isopropylacrylamide)/chitosan | camptothecin (anti-cancer) | -- | SW480 | direct dissolution | pH | [51] |
poly[2-(N,N-diethylamino)ethyl methacrylate]-block-PEG | cisplatin (anti-cancer) | -- | SKOV-3 In vivo | solvent displacement method | pH | [52] |
poly (lactide-co-glycolide)-PEG | curcumin (anti-cancer) | -- | KBM-5, Jurkat, DU145, MDA-MB-231, HCT116,SEG-1 In vivo | nanoprecipitation | -- | [53] |
polylactide-co-glycolide–PEG–folate | docetaxel (anti-cancer) | folate | SKOV3 | emulsification/solvent diffusion method | -- | [54] |
poly(D,L-lactic-co-glycolic acid)-block-PEG | docetaxel (anti-cancer) | PSMA aptamer | LNCaP | nanoprecipitation | -- | [55] |
glycol chitosan-5β-cholanic acid | docetaxel (anti-cancer) | -- | A549 In vivo | dialysis method | -- | [56] |
poly(l-histidine)-b-PEG-folate (75 wt.%) and poly(L-lactide)-b-PEG-folate (25 wt.%) | doxorubicin (anti-cancer) | folate | MCF-7 | . dialysis method | pH | [57] |
chitosan-poly(acrylic acid) | doxorubicin (anti-cancer) | -- | HepG2 In vivo | direct dissolution | -- | [58] |
poly(ε-caprolactone)-PEG-poly(ε-caprolactone) | honokiol (anti-inflammation) | -- | A549 | direct dissolution | -- | [59] |
ethylcellulose methylcellulose | nimesulide (nonsteroid anti-inflammation) | -- | fresh human blood | desolvation method | -- | [60] |
poly(ethylene oxide)-modified poly(ε-caprolactone) | tamoxifen | -- | MDA-MB-231 In vivo | solvent displacement | -- | [61] |
PEG-polycyanoacrylate | paclitaxel (anti-cancer) | transferrin | In vivo | solvent evaporation | -- | [62] |
poly (lactide-co-glycolide fumarate)/poly(lactide-co-ethylene oxide fumarate) poly (lactide-fumarate)/ poly(lactide-co-ethylene oxide fumarate) | paclitaxel (anti-cancer) | -- | HCT116 In vivo | dialysis method | -- | [63] |
PEG750-block-poly(ε-caprolactone-co-trimethylenecarbonate) | paclitaxel (anti-cancer) | -- | HeLa In vivo | solvent evaporation | -- | [64] |
poly (lactide-co-glycolide)/ poly(ε-caprolactone)-PEG | paclitaxel (anti-cancer) | -- | HeLa | simple emulsion or nanoprecipitation method | -- | [65] |
linoleic acid/poly(β-malic acid) Chitosan | paclitaxel (anti-cancer) | -- | In vivo | sonication and dialysis method | -- | [66] |
poly(β-amino ester)-graft-PEG | paclitaxel camptothecin (anti-cancer) | -- | SKOV-3 | solvent displacement or dialysis method | pH | [42] |
glycol chitosan-5β-cholanic acid | protophorphyrin IX (photosensitizer, photodynamic therapy) | -- | SCC7 In vivo Ex vivo | dialysis method | -- | [67] |
poly(β-benzyl-l-aspartate)-block-poly(vinylpyrrolidone) | prednisone (anti-inflammation) | -- | SW-1990 | dialysis method | pH | [68] |
poly (10-undecenoic acid-b-N-isopropylacrylamide) | prednisone (anti-inflammation) | -- | ECV304 | dialysis method | pH, temperature | [69] |
cellulose-g- poly(l-lactide) | prednisone (anti-inflammation) | -- | 3T3 | dialysis method | -- | [70] |
galactosylated polycaprolactone-g-dextran | prednisone (anti-inflammation) | galactose | HepG2, 3T3 In vivo | dialysis method | -- | [71] |
poly(ethylene oxide)-modified poly(ε-caprolactone) | saquinavir (HIV-protease inhibitor) | -- | THP-1 | solvent displacement | -- | [72] |
water soluble chitosan | thymol (anti-microbial) | -- | Staphylococcus aureus Bacillus subtilis Escherichia coli Aspergillus niger | sonication method | -- | [73] |
4.2. Protein, peptide and oligosaccharide delivery
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4.3. Vaccine delivery
Polymer | Antigen | Remarks | route | Ref |
---|---|---|---|---|
poly-l-lysine coated polystyrene particles | sOVA-C1 plasmid | Particles of different sizes may target different APCs. | intradermal | [113] |
poly-(ε-caprolactone) -poly(lactide-co-glycolide) | diphtheria toxoid | Correlations between polymer characteristic (e.g., hydrophobicity ) and route of administration, indicate that such characteristics can have interesting implications in immune responses. | intranasal intramuscular | [114] |
methoxyPEG–poly(lactide-co-glycolide) | recombinant hepatitis B surface antigen (HBsAg) | Delivery of HBsAg encapsulated within a nanoparticle is a superior way for generating faster immune responses, as compared to the non-encapsulated counterpart. | intraperitoneal | [115] |
poly lactic acid-PEG | recombinant hepatitis B surface antigen (HBsAg) | Different compositions of PLA and PEG polymers were synthesized to stabilize the antigen. A comparison of their efficacy in the generation of an effective immune responses is shown. | nasal | [5] |
poly(γ-glutamic acid)-graft-L-phenylalanine | japanese encephalitis (JE) vaccine | A single dose of JE vaccine with nanoparticles enhanced the neutralizing antibody titer. | intraperitoneal | [116] |
poly(γ-glutamic acid)-graft-l-phenylalanine | influenza hemagglutinin (HÁ) vaccine | Subcutaneous immunization with a mixture of HA vaccine and nanoparticles induced higher mononuclear cell proliferation and production of IFN-γ, IL-4, and IL-6 upon HA restimulation. | subcutaneous | [117] |
poly (d,l-lactide-co-glycolide)–polyethyleneimine | DNA encoding Mycobacterium tuberculosis latency antigen Rv1733c | The polyplexes were able to mature human dendritic cells and stimulated the secretion of cytokines, comparable to levels observed after lipopolysaccharide stimulation. | intramuscularly endotracheal | [118] |
hydrophobically modified poly(γ-glutamic acid) | gp120 (human immunodeficiency virus -1) | The protein-encapsulated nanoparticles induced cytotoxic T lymphocyte. Efficient uptake by immature dendritic cells (DC) and induction of DC maturation was observed. | intranasal | [25] |
chitosan | DNA vaccine encoding mite dust allergen Der p 2 (Der p 2-pDNA) | Chitosan-DNA nanoparticles can generate a higher level expression of gene in vivo, therefore can preferentially activate specific Th1 immune responses thus preventing subsequent sensitization of Th2 cell-regulated specific IgE responses. | oral | [119] |
chitosan | plasmid DNA encoding surface protein of Hepatitis B virus (pRc/CMV-HBs(S)) | Administration of nanoparticles resulted in serum anti-HBsAg titer and induced sIgA titre in mucosal secretions. Chitosan nanoparticles were able to induce humoral mucosal and cellular immune responses. | nasal | [120] |
chitosan | DNA plasmids expressing different M. tuberculosis epitopes | Chitosan nanoparticles protect DNA from degradation by nucleases, induce dendritic cells maturation and increased IFN-γ secretion from T cells. | pulmonary | [121] |
chitosan | pcDNA3-VP1, encoding VP1, major structural protein of coxsackievirus (CVB3) | Nasal administrated chitosan–DNA produced higher levels of serum IgG and mucosal secretory IgA. Strong cytotoxic T lymphocyte activities helped to effectively eliminate CVB3 viruses. | intranasal | [122] |
low molecular weight chitosan (LMWC) | plasmid DNA encoding human cholesteryl ester transfer protein C-terminal fragment (CEPT) | LMWC had lower binding affinity to DNA, but mediated higher transfection efficiency. Polyplexes could elicit significant systemic immune responses, modulate the plasma lipoprotein profile and attenuate the progression of atherosclerosis. | intranasal | [123] |
mono-N-carboxymethyl chitosan (MCC) N-trimethyl chitosan (TMC) | tetanus toxoid | Surface charge and particle size exert an important influence in the production of an enhanced immune response. | intranasal | [112] |
4.4. Gene delivery
Polymer | Therapeutic agent | Ligand | Remarks | Ref |
---|---|---|---|---|
chitosan | sense or antisense oligodeoxynucleotides (ODNs) against malarial topoisomerase II gene | -- | Antisense-nanoparticles demonstrate a significant higher inhibition of human malaria parasite, as comparison with sense-nanoparticles and free ODNs. More easily dissociated complexes mediate a faster onset of action. | [146] |
folate-N-trimethyl chitosan | pDNA | folate | Folate conjugation increased intracellular uptake , transfection efficiency and induce endosomal escape. | [147] |
folic acid-chitosan | pDNA (pVR1412) | folate | Nanoparticle with positive zeta potentials interact with the cell membrane allowing their endocytosis. | [148] |
galactosylated 6-amino-6-deoxychitosan | pDNA (pCMV-Luc) | galactose | The increase of transfection efficiency of Gal-6ACT was therefore likely due to improvements in intracellular trafficking and not due to the increase of cellular uptake., | [149] |
chitosan/hyaluronic acid | pDNA(pEGFP-C1, pβ-gal) | hyaluronan | Polyplexes were able to provide high transfection without affecting cell viability, entering the corneal epithelial cells by CD44 receptor–mediated endocytic uptake. | [150] |
mannosylated chitosan | pDNA (pGL3-Luc) | mannose | Cellular uptake mediated by mannose recognition. Reduced toxicity and high transfection efficiency. | [151] |
chitosan –IL-1Ra folate- IL-1Ra- Chitosan | IL-1Ra plasmid DNA | folate | Folate-chitosan-DNA nanoparticles containing the IL-1 Ra gene prevent bone damage and inflammation in rat adjuvant-induced arthritis model that overexpress folate receptors. | [152] |
PEG-Chitosan | pDNA (pRE-luciferase; pREP4;pCMV-luciferase) | transferrin KNOB protein | The transfection efficiency was much impressive with KNOB (130-fold improvement), in HeLa cells. Chitosan exhibited limited buffering capacity. The clearance of the PEGylated nanoparticles was slightly slower than that of the unmodified nanoparticles. | [153] |
chitosan | plasmid pGL3-Luc | -- | Polyplexes are endocytosed and possibly released from endosomes due to swelling of both lysosomes and polyplexes, causing the endosome rupture. | [154] |
chitosan | pDNA (pAAV-tetO-CMV-mEpo and pCMVβ) | -- | Oral gene therapy was efficient in delivering genes to enterocytes. | [155] |
thiolated chitosan | pDNA (pEGFP-N2) | -- | Improved gene delivery in vitro as well as in vivo. The extended pDNA release and subsequent gene expression were achieved by oxidation of introduced thiol groups to crosslink the thiolated chitosan. | [156] |
quaternized (trimethylated) chitosan oligomer | pDNA (pEGFcp1-GFP) | -- | Transfection efficiency decreases increasing the degree of quaternization. The polymer effectively transfers the GFP gene into cells both in vitro and in vivo. | [157] |
6-N,N,N-trimethyltriazole chitosan | pDNA (EGFP-N1 | -- | The presence of the trimethyltriazole group led to significantly increased cellular uptake, which resulted in higher transfection efficiency in HEK 293 and MDA-MB-468 cells. | [158] |
methoxy PEG–PEI–chitosan | pDNA (pVRfat-1) | -- | The mPEG increased the slow-releasing ability and water solubility, while PEI improved the transfection efficiency. | [159] |
chitosan/ poly(γ-glutamic acid) | pDNAs (pEGFP-N2, pGL4.13 and pEGFP-N2) | -- | The incorporation of γ-PGA in the chitosan nanoparticles facilitates the dissociation of chitosan and DNA, increasing transfection efficiency. Trypsin-cleavable proteins in cellular membrane affect internalization of polyplexes. | [160] |
methylated collagen | pDNA (pRELuc) | -- | Methylated collagen improved DNA binding ability and the stability of the complexes at physiological conditions, as compared with unmodified native collagen. | [161] |
cationized gelatin | plasmid DNA of transforming growth factor-βR (TGF-βR) siRNA expression vector | -- | The injection of polyplexes significantly decreased the level of TGF-βR and α-smooth muscle actin over-expression, the collagen content of mice kidney, and the fibrotic area of renal cortex, in contrast to free plasmid DNA injection. | [162] |
PEG–modified thiolated gelatin | pDNA (EGFP-N1) | -- | Nanoparticles released encapsulated plasmid DNA in response to varying concentrations of glutathione. | [163] |
Polymer | Therapeutic agent | Ligand | Remarks | Ref |
---|---|---|---|---|
PEG-PEI (NanoGelTM) | antisense oligonucleotide (ODN) targeting the mdr1 gene | transferrin insulin | Transport efficacy across the blood-brain barrier is increased by modification with transferrin or insulin. Improvement of ODN accumulation in the brain (15 fold). | [9] |
lactoferrin-PEI | pDNA | lactoferrin | Selectivity for bronchial epithelial cells. Lower cellular toxicity of polyplexes and higher transfection efficiency (5-fold higher), as compared with PEI/pDNA complexes. | [170] |
RGD-PEG-PEI | siRNA inhibiting vascular endothelial growth factor receptor-2 | RGD | Selective tumor uptake, siRNA sequence-specific inhibition of protein expression within the tumor and inhibition of both tumor angiogenesis and growth rate. | [44] |
PEI-g-PEG-RGD | pDNA (pCMV-sFlt-1) | RGD | Efficient inhibition on proliferation of endothelial cells that expressed sFlt-1 predominantly bound to exogenous VEGF and blocked the binding of VEGF to the full-length Flt-1 receptor. | [171] |
siRNA-PEG-LHRH/PEI | siRNA (VEGF-vascular endothelial growth factor) | luteinizing hormone- releasing hormone (LHRH) | Enhancement of cellular uptake, as compared to those without LHRH, resulting in increased VEGF gene silencing efficiency via receptor-mediated endocytosis. | [172] |
EGF-PEG-PEI | pDNA (pCMVLuc) | epidermal growth factor (EGF) peptides | EGF-containing polyplexes were 10- to 100-fold more efficient than polyplexes without EGF. | [173] |
PEI | pDNA | Peptide (NL4-10K) | Polyplexes displayed no toxicity in neuronal cells. Enhancement of gene expression (up to 1000-fold) and transfection efficiency (59-fold higher), in dorsal root ganglia, compared to nontargeting polyplexes. | [174] |
PEI-g-Clenbuterol | pDNA (pCMVLuc) | β2-adrenoceptor (clenbuterol) | Specific cellular uptake into alveolar (transfection efficiency 14-fold higher than for unmodified PEI) but not bronchial epithelial cells. | [175] |
folate–PEG–PEI | pDNA (pCMV-Luc or pcDNA/rev-caspase-3) | folate | Higher transfection efficiency than other commercially available transfection agents. | [176] |
PEI-PEG-Fab’ | pDNA (pCMVLuc) | anti- glutamic acid decarboxylase (GAD) | Selectivity toward the islet cells. High transfection efficiency in GAD-expressing mouse insulinoma cells. | [177] |
HerPEI | pDNA(pcDNA3-CMV-Luc) | anti-HER2 | The HerPEI polyplexes showed significantly greater transfection activity (up to 20-folds) than nonderivatized PEI-based polyplexes in the HER2 overexpressing breast cancer cells. | [178] |
mannose-PEI | pDNA | mannose | Dendritic cells transfected with polyplexes containing adenovirus particles are effective in activating T cells of T cell receptor transgenic mice in an antigen-specific fashion. | [179] |
methoxypolyethyleneglycol-PEI-cholesterol | pDNA (pmIL-12) | -- | Inhibition of tumor growth enhanced when combined with specific chemotherapeutic agents. | [180] |
dextran-PEI | pDNA | -- | Stability of the complex in the presence of BSA. The transfection efficiency depended on the molecular weight of dextran and the grafting degree. | [181] |
acid-labile PEI | pDNA (pCMV-Luc) | -- | The acid-labile PEI was much less toxic and showed comparable transfection efficiency to that of PEI25K. Polyplexes may be rapidly degraded in acidic endosome. | [182] |
disulfide-crosslinked low molecular weight linear PEI- sodium hyaluronate | pDNA (pBR322, pEGFP-C1) | -- | Polyplexes achieved significantly higher transfection efficiency than other polymer systems, especially in the presence of serum. | [183] |
galactosylated PLL | pDNA (pCAT) | galactose | Hepatoma cell line revealed high gene expression. After intravenous injection, polyplexes were rapidly eliminated from the circulation and preferentially taken up by the liver’s parenchymal cells. | [184] |
Lactosylated PEG-siRNA/PLL | RNAi | lactose | pH-responsive and targetable polyplexes exhibited significant gene silencing human hepatoma cells. | [185] |
AWBP-PEG-PLL | pDNA (pMNK) | Artery wall binding peptide (AWBP) | High transfection efficiency in bovine aorta endothelial cells and smooth muscle cells. | [186] |
Antibody-PLL | pDNA(pSV-b-galactosidase) | Anti JL1 | Polyplexes internalization into Molt 4 cells and human leukemia T cells. Higher in vitro transfection efficiency than polyplexes without targeting ligand. | [187] |
RGD-PEG-block-PLL | pDNA | RGD | Synergistic effect of cyclic RGD peptide and disulfide cross-links to exert the smooth release of pDNA in the intracellular environment via reductive cleavage. Enhanced transfection efficiency against HeLa cells, due to a change in their intracellular trafficking route. | [188] |
Polymer | Therapeutic agent | Remarks | Ref |
---|---|---|---|
poly(imidazole/ 2-dimethylaminoethylamino)phosphazene | pDNA | Imidazole effect on cytotoxicity and transfection efficiency. Evaluation of half-lives under neutral and acidic conditions. | [144] |
poly[α-(4-aminobutyl)-L-glycolic acid] (PAGA) | pDNA( pCAGGS-Il10, pCAGGS-Il4) | Combined administration of mouse Il4 and Il10 plasmids prevents the development of autoimmune diabetes in non-obese diabetic mice. | [191] |
poly(4-hydroxy-L-proline ester) | pDNA(CMV-βGal) | The minimum viability of cells incubated with poly(4-hydroxy-L-proline ester) was 85%, which is excellent when compared to the cases of polylysine (20%) and polyethylenimine (2%). | [192] |
poly(amido amine)s containing multiple disulfide linkages | pDNA | Buffer capacity of poly(amido amine)s in the pH range 7.4-5.1. High transfection efficiency and gene expression, in the presence of serum. | [193] |
cationic amphoteric polyamidoamine | pDNA (pEGFP) | Evaluation of toxicity and hemolytic activity in the pH range 4.0-7.4. Circulation time and organ accumulation assessment. Study of complex stability and transfection efficiency | [194] |
three blocks of amino acids Ac-(AF)6-H5-K15-NH2 (FA32) | Doxorubicin, pCMV-luciferase, pCMV-p53 | Co-delivery of drug and gene using nanoparticles was demonstrated via confocal imaging, luciferase expression in the presence of doxorubicin, and synergy in cytotoxic effect towards HepG2 cells. | [166] |
N,N-diethylethylenediamine-polyurethane | pDNA (pCMV-βgal) | Cytotoxicity was substantially lower and transfection efficiency comparable to the well-known gene carrier poly(2-dimethylaminoethyl methacrylate | [195] |
5. Conclusion
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Gonçalves, C.; Pereira, P.; Gama, M. Self-Assembled Hydrogel Nanoparticles for Drug Delivery Applications. Materials 2010, 3, 1420-1460. https://doi.org/10.3390/ma3021420
Gonçalves C, Pereira P, Gama M. Self-Assembled Hydrogel Nanoparticles for Drug Delivery Applications. Materials. 2010; 3(2):1420-1460. https://doi.org/10.3390/ma3021420
Chicago/Turabian StyleGonçalves, Catarina, Paula Pereira, and Miguel Gama. 2010. "Self-Assembled Hydrogel Nanoparticles for Drug Delivery Applications" Materials 3, no. 2: 1420-1460. https://doi.org/10.3390/ma3021420
APA StyleGonçalves, C., Pereira, P., & Gama, M. (2010). Self-Assembled Hydrogel Nanoparticles for Drug Delivery Applications. Materials, 3(2), 1420-1460. https://doi.org/10.3390/ma3021420