Cell Penetrating Peptides in the Delivery of Biopharmaceuticals
Abstract
:1. Introduction
2. Classification of Cell Penetrating Peptides
2.1. Classification based on Linkage with Therapeutic Agent
2.1.1. Covalent Bonded CPPs
2.1.2. Non-covalent Bonded CPPs
2.2. Classification based on Chemical Charge Induced by CPP
2.2.1. Cationic
2.2.2. Amphipathic
3. Cell Penetrating Peptides in Biopharmaceuticals
3.1. Gene Delivery
3.2. siRNA Delivery
3.3. Antisense Oligonucleotide Delivery
3.4. Protein Delivery
3.5. Delivery of Drug Carriers
3.6. CPP as Active Pharmaceutical Ingredients
4. Advances in Cell Penetrating Peptide Development
- a.)
- PsorBan® a cyclosporine-poly-arginine conjugate for the topical treatment of psoriasis was the first CPP mediated therapeutic agent which entered phase II trials in 2003 (CellGate, Inc.)., Delcasertib as KAI-9803 was recently tested by Kai Pharmaceutical as a TAT-protein kinase C inhibitor peptide modulator of protein kinase C for acute myocardial infarction and cerebral ischemia, and orally administrated cyclosporine A (CsA), effective against a broad range of inflammatory skin diseases including psoriasis, are examples of ongoing preclinical studies on effective delivery strategies [55]. Conjugation of a CPP, heptaarginine with CsA through a linker designed to release the active compound at the pH of the tissue has been shown to enhance its topical absorption, inhibiting cutaneous inflammation [56].
- b.)
- Avi Biopharma is working on the clinical development of CPPs for the in vivo steric block splicing correction using 6-aminohexanoic acid spaced oligoarginine [(RAhx-R)4]. It consists of a Morpholino oligo conjugated with the CPP [(RXR)4-XB-CPP]. The goal of this conjugate is to prevent eventual blockage of a transplanted vein after cardiovascular bypass surgery [57]. Several other companies including Traversa Inc., and Panomics Inc. are also evaluating CPPs in preclinical and clinical trials in addition to other molecules conjugated to CPPs which are being optimized [58].
5. Chemical Modification of CPP for Enhanced Delivery
5.1. Amino Acid Substitution
5.2. Functional Group Modification
6. Conclusions
Acknowledgement
References
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Munyendo, W.L.; Lv, H.; Benza-Ingoula, H.; Baraza, L.D.; Zhou, J. Cell Penetrating Peptides in the Delivery of Biopharmaceuticals. Biomolecules 2012, 2, 187-202. https://doi.org/10.3390/biom2020187
Munyendo WL, Lv H, Benza-Ingoula H, Baraza LD, Zhou J. Cell Penetrating Peptides in the Delivery of Biopharmaceuticals. Biomolecules. 2012; 2(2):187-202. https://doi.org/10.3390/biom2020187
Chicago/Turabian StyleMunyendo, Were LL, Huixia Lv, Habiba Benza-Ingoula, Lilechi D. Baraza, and Jianping Zhou. 2012. "Cell Penetrating Peptides in the Delivery of Biopharmaceuticals" Biomolecules 2, no. 2: 187-202. https://doi.org/10.3390/biom2020187
APA StyleMunyendo, W. L., Lv, H., Benza-Ingoula, H., Baraza, L. D., & Zhou, J. (2012). Cell Penetrating Peptides in the Delivery of Biopharmaceuticals. Biomolecules, 2(2), 187-202. https://doi.org/10.3390/biom2020187