Challenges of Current Anticancer Treatment Approaches with Focus on Liposomal Drug Delivery Systems
Abstract
:1. Introduction
Cancer Statistics: Need for Better Therapeutics
2. Limitations and Challenges Associated with Traditional Anticancer Therapies
2.1. Cancer Surgery
2.2. Chemotherapy
2.3. Radiotherapy
3. Targeted Drug Delivery Systems and Their Limitations
3.1. Active Tumor Targeting Approach
3.1.1. Antibody and Antibody Fragments
3.1.2. Immunotoxins and Immunoconjugates
3.1.3. Immunoliposomes
3.1.4. Manufacturing and Clinical Challenges of Active Targeting
3.2. Passive Tumor Targeting Approach
3.2.1. Traditional Liposomes
3.2.2. Stealth Liposome
3.2.3. Requirements of Stimuli Induced Drug Release
Ultrasound Induced Triggered Release
Light Induced Triggered Release
Hyperthermia Induced Triggered Release
Triggered Release by Magnetic Field from Magnetic Liposomes
3.3. Manufacturing and Clinical Challenges Common to Both Active and Passive Targeting
4. Need for Better Pre-Clinical and Clinical Strategies
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Active Ingredient/s | Trade/Brand Name | Liposome Composition | Active/Passive Targeting | Route of Administration | Indication | Ref. |
---|---|---|---|---|---|---|
Hwtp53 DNA | SGT-53 | DOTAP/DOPE | Active (Anti-Transferrin scFv) | IV, in vivo, clinical | Solid tumors | [13,14,15] |
Docetaxel prodrug | MM-310 | Egg derived sphingomyelin/ CH | Active (Anti-Ephrin receptor A2) | IV, in vivo, clinical | Solid tumors | [16,17,18,19] |
DOX | C225-ILs-dox | DSPC/CH/mPEG-DSPE | Active (Anti-EGFR Fab fragment from mAb C225 (cetuximab)) | IV, in vivo, clinical | Glioblastoma | [15,19,20,21] |
DOX | MM-302 | HSPC/CH/DSPE-PEG | Active (Anti-HER2 antibody) | IV, in vivo, clinical | Breast cancer | [22,23] |
Melanoma antigens + interferon-gamma | Lipovaxin-MM | POPC/Ni-3NTA-DTDA | Active (Single domain antibody (dAb) fragment (VH)) | IV, in vivo, clinical | Malignant melanoma | [15,24] |
RB94 plasmid DNA | SGT-94 | DOTAP/DOPE | Active (Anti-Transferrin Antibody fragment (scFv)) | IV, in vivo, clinical | Solid tumor | [15,25,26,27] |
DOX | 2B3-101 | HSPC/CH/DSPE-PEG | Active (Glutathione ligand) | IV, in vivo, clinical | Active brain metastasis, meningeal carcinomatosis | [18,28,29] |
Tetrandrine + vincristine | - | EPC/CH/DSPE-PEG 2000 | Active (Transferrin ligand) | IV, in vivo in mice | Brain glioma | [19,30] |
Bleomycin | - | DOPE/CH | Active (Folic acid ligand) | In vitro | Cervical and breast cancer cell lines | [19,31] |
DOX | - | DOPE/DOPC/Lecithin | Active (Glycoprotein ligand) | IV, in vivo in mice | Mouse melanoma cells | [32] |
ATRA | - | DPPC/CH/DSPE-mPEG2000 | Passive | In vitro | Human thyroid carcinoma cell lines | [33] |
ATRA | - | DOTAP/CH | Passive | In vivo in mice, IV | Lung cancer | [34] |
Daunorubicin + Cytarabine | VYXEOS | DSPG/DSPC/CH | Passive | IV, in vivo, FDA approved | Secondary acute myeloid leukemia (sAML) | [15,35,36,37] |
Paclitaxel | LEP-ETU | DOPC/CH/cardiolipin | Passive | IV, in vivo, FDA approved | Ovarian cancer | [38,39] |
Vincristine | - | Sphingomyelin/CH | Passive | IV, in vivo, clinical | Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) | [40,41,42] |
Verteporfin | Visudyne | DMPC/EPG | Passive | IV, in vivo, clinical | EGFR-mutated glioblastoma | [43,44,45] |
DOX | ThermoDox | DPPC/MSPC/PEG 2000-DSPE | Passive | IV, in vivo, clinical | Hepatocellular carcinoma (HCC) | [46,47] |
Paclitaxel | EndoTAG-1 | DOTAP/DOPC | Passive | IV, in vivo, clinical | Pancreatic cancer | [38,48] |
miR-34a | - | DOTAP/CH | Passive | IV, in vivo, clinical | Advanced solid tumors | [40,49,50,51] |
Irinotecan | ONIVYDE | DSPC/DSPE/CH/mPEG-2000 | Passive | IV, in vivo, FDA approved | Metastatic adenocarcinoma of the pancreas | [52,53] |
Mitomycin-C prodrug | Promitil | HSPC/CH/DSPE-PEG | Passive | IV, in vivo, clinical | Solid tumors | [54,55,56] |
TUSC2/FUS1 | REQORSA | DOTAP/CH | Passive | IV, in vivo, clinical | Non-Small cell lung cancer | [57,58] |
Eribulin mesylate | E7389-LF | HSPC/CH/PEG 2000-DSPE | Passive | IV, in vivo, clinical | Solid tumors | [15,59,60] |
Navelbine | - | DSPC/CH/PEG -DSPE | Passive | In vivo in mice | Colorectal cancer cells | [61] |
Curcumin | Lipocurc | DMPG/DMPC | Passive | IV, in vivo, clinical | Metastatic tumors | [62,63,64] |
Paclitaxel | PTX–LDE | Cholesteryl oleate/Egg-PC/Miglyol 812/CH | Passive | IV, in vivo, clinical | Ovarian carcinoma | [65,66,67] |
PKN3 siRNA | Atu027 | AtuFECT01/DPhyPE/DSPE-PEG-2000 | Passive | IV, in vivo, clinical | Pancreatic cancer | [25] |
Active and Passive Targeting Challenges | |
---|---|
1. | Scale up liposome preparation to reproducibly achieve target product profile including in vitro drug release rate, particle size distribution, lamellarity, stability, drug encapsulation efficiency, etc. |
2. | Separation of raw lipids in a mixture of lipids and ability to analyze them |
3. | Determination of complete stability and toxicity profile of novel lipids involved in formulations |
4. | Stability of liposomes in solution |
5. | Determination of biodistribution of liposomes appropriate PK/PD models to predict parameters in humans |
6. | Immunogenic reactions such as CARPA upon IV administration of liposomes have resulted in additional layer of challenge |
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Gyanani, V.; Haley, J.C.; Goswami, R. Challenges of Current Anticancer Treatment Approaches with Focus on Liposomal Drug Delivery Systems. Pharmaceuticals 2021, 14, 835. https://doi.org/10.3390/ph14090835
Gyanani V, Haley JC, Goswami R. Challenges of Current Anticancer Treatment Approaches with Focus on Liposomal Drug Delivery Systems. Pharmaceuticals. 2021; 14(9):835. https://doi.org/10.3390/ph14090835
Chicago/Turabian StyleGyanani, Vijay, Jeffrey C. Haley, and Roshan Goswami. 2021. "Challenges of Current Anticancer Treatment Approaches with Focus on Liposomal Drug Delivery Systems" Pharmaceuticals 14, no. 9: 835. https://doi.org/10.3390/ph14090835