Smart Drug Delivery Systems Based on Cyclodextrins and Chitosan for Cancer Therapy
Abstract
:1. Introduction
2. Characteristics of Biopolymers as Versatile Materials for Drug Delivery
2.1. Cyclodextrins (CDs)
2.2. Chitosan (CS)
3. Stimuli-Responsive Polymers Based on Cyclodextrins (CDs)
3.1. Folate-Responsive CD-Based Delivery Systems
3.2. Glutathione (Redox-Responsive) CD-Based Delivery Systems
3.3. pH-Modulated Drug Release from CD-Based Delivery Systems
4. Stimuli-Responsive Polymers Based on Chitosan (CS)
4.1. Folate-Responsive CS-Based Delivery Systems
4.2. Glutathione (Redox-Responsive) CS-Based Delivery Systems
4.3. pH-Modulated Drug Release from CS-Based Delivery Systems
5. Summative Discussion
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
5-FU | 5-fluorouracil |
APTES | 3-triethoxysilylpropylamine |
C-FA-PNPs | folic acid–chitosan-modified PLGA nanoparticles |
CDDP | Cis-dichlorodiammine-platinum |
CDs | cyclodextrins |
CS | chitosan |
DHA | dihydroartemisinin |
DOX | doxorubicin |
EE% | encapsulation efficiency |
EPI | epichlorohydrin |
EPI-β-CD | epichlorohydrin-βCD |
EPR | enhanced permeability and retention |
FA | folic acid |
FCCNPs | folate-conjugated chitosan nanoparticles |
FR | folate receptor |
GSH | glutathione |
HP-β-CD | 2-hydroxypropyl-β-cyclodextrin |
IL-2 | interleukin-2 |
IRI | irinotecan |
LDH | lactate dehydrogenase |
MDR | multidrug resistance |
MDSCs | myeloid suppressor cells |
MSNs | mesoporous silica nanoparticles |
MTX | methotrexate |
NO | nitric oxide |
NPs | nanoparticles |
NS | nanosponge |
ODA | octadecylamine |
OMT | oxymatrine |
PCL | poly(ε-caprolactone) |
PD-L1 | programmed death-ligand 1 |
PEG | poly(ethylene glycol) |
PTX | paclitaxel |
QTN | quercetin |
R848 | resiquimod |
GPNP | GSH and pH dual-responsive nanoplatform |
RB | Rose Bengal |
ROS | reactive oxygen species |
SBE-β-CD | sulfobutylether-β-cyclodextrin |
SFN | sorafenib |
SFRP1 | secreted frizzled-related protein 1 |
SNAP | S-nitroso-N-acetylpenicillamine |
TME | tumor microenvironment |
TPP | tripolyphosphate |
α-CD | alpha-cyclodextrin |
β-CD | beta-cyclodextrin |
γ-CD | gamma-cyclodextrin |
ε-CL | ε-caprolactone |
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Drug Delivery System | Carried Agent(s) | Type of Cancer | Targeting Receptor/ Stimuli | Main Observations | Ref. |
---|---|---|---|---|---|
Folate-conjugated β-CD-polycaprolactone | curcumin | cervical cancer | pH temperature folate receptor |
| [78] |
PEG-coated β-CD-based NPs (CD-PEG-FA.Rg3.QTN) | ginsenoside (Rg3) quercetin (QTN) | colorectal cancer | folate receptor |
| [79] |
Polymeric micelle, β-CD-g-PCL-SS-PEG-FA | doxorubicin (DOX) | cervical cancer/MDR1 hepatocellular carcinoma/MDR1 | GSH folate receptor |
| [83] |
β-CD-based nanosponge (NS) | doxorubicin (DOX) 6-coumarin | hepatocellular carcinoma | GSH pH |
| [85,87] |
ROS-generating NPs (TA-β-CD@DHA NPs) | dihydroartemisinin (DHA) | colon carcinoma | pH GSH |
| [91] |
Pt(IV)-SSNPs | cisplatin as Pt(IV)-ADA2 prodrug | colon carcinoma | GSH |
| [93] |
5-FU/IL-2/CD nanoplexes | 5-fluorouracil (5-FU) interleukin-2 (IL-2) | colorectal cancer | pH |
| [98] |
Epichlorohydrin (EPI)- β-CD hydrogel | 5-fluorouracil (5-FU) methotrexate (MTX) | breast cancer | pH |
| [110] |
Sulfobutyl ether-β-cyclodextrin complex (MF-SEBCD) | 5-fluorouracil (5-FU) methotrexate (MTX) | colorectal cancer | pH |
| [119] |
pCyD/SFN and oCyD/SFN | sorafenib (SFN) | breast cancer hepatocellular carcinoma gastric cancer melanoma colon carcinoma | pH |
| [120] |
β-cyclodextrin or hydroxypropyl-β-cyclodextrin thermosensitive gel | 5-fluorouracil (5-FU) | HPV-induced cervical cancers | pH temperature |
| [122] |
Drug Delivery System | Carried Agent(s) | Type of Cancer | Targeting Receptor/Stimuli | Main Observations | Ref. |
---|---|---|---|---|---|
Chitosan (CS)-poly lactic-co-glycolic acid (PLGA)-folic acid (FA) nanocarrier (CPSF) | sorafenib (SFN) | lung cancer | pH folate receptor |
| [70] |
Poly(lactic-co-glycolic acid), chitosan, polyethylene glycol, and folic acid microbubbles | methotrexate (MTX) | breast cancer | folate receptor |
| [129] |
Folate-conjugated chitosan nanoparticles (FCCNPs) | cytarabine | breast cancer | folate receptor |
| [131] |
FA-CS-modified PLGA nanoparticles (C-FA-PNPs) | irinotecan (IRI) and quercetin (QTN) | colon cancer | folate receptor |
| [133] |
Carboxymethyl-CS-nanosystem | Rose Bengal (RB) and oxymatrine (OMT) | oral cancer | GSH |
| [140] |
CS-based GPNPs (GSH and pH dual-responsive nanoplatform) | doxorubicin (DOX) and resiquimod (R848) | breast cancer, treatment-resistant | pH GSH |
| [142] |
CS polymeric micelles (TSCO–SS–ODA/DOX) | doxorubicin (DOX) | breast cancer | GSH |
| [143] |
CS Microspheres | 5-fluorouracil (5-FU), paclitaxel (PTX), and Cis-dichlorodiammine-platinum (CDDP) | osteosarcoma | pH |
| [149] |
CS-based magnetic nanoparticles (MNPs) conjugated with FA and functionalized with succinic anhydride (CS-FA/CS-SA@MNPs) | doxorubicin (DOX) | osteosarcoma | pH folate receptor |
| [150] |
CS-modified mesoporous silica NPs (MSNs) modified with 3-triethoxysilylpropylamine (APTES) | methotrexate (MTX) | breast cancer | pH |
| [151] |
Fluorinated Carboxymethyl chitosan-based nano-prodrugs (F-NGs) | prodrug (Pt(IV)-1)-containing cisplatin (DDP) and demethylcantharidin (DMC) at a molar ratio of 1:2 | hepatocellular carcinoma lung cancer breast cancer | pH GSH |
| [152] |
FA-CSNPs | thymoquinone | ovarian cancer | folate receptor |
| [153] |
CS-FA-Hesperetin (CFH) NPs | doublecortin like kinase 1 antibody (DCLK1) and hesperetin | colon cancer | folate receptor |
| [154] |
Lipid CS hybrid NPs | cisplatin | breast cancer ovarian cancer | folate receptor |
| [155] |
CS/stearic acid NPs (CSSA NPs) | doxorubicin (DOX) curcumin | colorectal cancer | GSH |
| [156] |
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Păduraru, L.; Panainte, A.-D.; Peptu, C.-A.; Apostu, M.; Vieriu, M.; Bibire, T.; Sava, A.; Bibire, N. Smart Drug Delivery Systems Based on Cyclodextrins and Chitosan for Cancer Therapy. Pharmaceuticals 2025, 18, 564. https://doi.org/10.3390/ph18040564
Păduraru L, Panainte A-D, Peptu C-A, Apostu M, Vieriu M, Bibire T, Sava A, Bibire N. Smart Drug Delivery Systems Based on Cyclodextrins and Chitosan for Cancer Therapy. Pharmaceuticals. 2025; 18(4):564. https://doi.org/10.3390/ph18040564
Chicago/Turabian StylePăduraru, Larisa, Alina-Diana Panainte, Cătălina-Anișoara Peptu, Mihai Apostu, Mădălina Vieriu, Tudor Bibire, Alexandru Sava, and Nela Bibire. 2025. "Smart Drug Delivery Systems Based on Cyclodextrins and Chitosan for Cancer Therapy" Pharmaceuticals 18, no. 4: 564. https://doi.org/10.3390/ph18040564
APA StylePăduraru, L., Panainte, A.-D., Peptu, C.-A., Apostu, M., Vieriu, M., Bibire, T., Sava, A., & Bibire, N. (2025). Smart Drug Delivery Systems Based on Cyclodextrins and Chitosan for Cancer Therapy. Pharmaceuticals, 18(4), 564. https://doi.org/10.3390/ph18040564