Quantifying molecular partition of cell-penetrating peptide-cargo supramolecular complexes into lipid membranes: optimizing peptide-based drug delivery systems

2013 ◽  
Vol 19 (4) ◽  
pp. 182-189 ◽  
Author(s):  
João Miguel Freire ◽  
Ana Salomé Veiga ◽  
Beatriz G. de la Torre ◽  
David Andreu ◽  
Miguel A. R. B. Castanho
Drug Delivery ◽  
2011 ◽  
Vol 18 (5) ◽  
pp. 377-384 ◽  
Author(s):  
Erez Koren ◽  
Anjali Apte ◽  
Rupa R. Sawant ◽  
Jacob Grunwald ◽  
Vladimir P. Torchilin

2020 ◽  
Vol 21 (20) ◽  
pp. 7502
Author(s):  
Ona Illa ◽  
José-Antonio Olivares ◽  
Nerea Gaztelumendi ◽  
Laura Martínez-Castro ◽  
Jimena Ospina ◽  
...  

Two series of new hybrid γ/γ-peptides, γ-CC and γ-CT, formed by (1S,2R)-3-amino-2,2,dimethylcyclobutane-1-carboxylic acid joined in alternation to a Nα-functionalized cis- or trans-γ-amino-l-proline derivative, respectively, have been synthesized and evaluated as cell penetrating peptides (CPP) and as selective vectors for anti-Leishmania drug delivery systems (DDS). They lacked cytotoxicity on the tumoral human cell line HeLa with a moderate cell-uptake on these cells. In contrast, both γ-CC and γ-CT tetradecamers were microbicidal on the protozoan parasite Leishmania beyond 25 μM, with significant intracellular accumulation. They were conjugated to fluorescent doxorubicin (Dox) as a standard drug showing toxicity beyond 1 μM, while free Dox was not toxic. Intracellular accumulation was 2.5 higher than with Dox-TAT conjugate (TAT = transactivator of transcription, taken as a standard CPP). The conformational structure of the conjugates was approached both by circular dichroism spectroscopy and molecular dynamics simulations. Altogether, computational calculations predict that the drug-γ-peptide conjugates adopt conformations that bury the Dox moiety into a cavity of the folded peptide, while the positively charged guanidinium groups face the solvent. The favorable charge/hydrophobicity balance in these CPP improves the solubility of Dox in aqueous media, as well as translocation across cell membranes, making them promising candidates for DDS.


2021 ◽  
Vol 9 (1) ◽  
pp. 1-7
Author(s):  
Vatsal R. Shah ◽  
Yamini D. Shah ◽  
Mansi N. Athalye

Therapeutic cargos which are impermeable to the cell can be delivered by cell penetrating peptides (CPPs). CPP-cargo complexes accumulate by endocytosis inside the cells but they fail to reach the cytosolic space properly as they are often trapped in the endocytic organelles. Here the CPP mediated endosomal escape and some strategies used to increase endosomal escape of CPP-cargo conjugates are discussed with evidence. Potential benefits can be obtained by peptides such as reduction in side effects, biocompatibility, easier synthesis and can be obtained at lower administered doses. The particular peptide known as cell penetrating peptides are able to translocate themselves across membrane with the carrier drugs with different mechanisms. This is of prime importance in drug delivery systems as they have capability to cross physiological membranes. This review describes various mechanisms for effective drug delivery and associated challenges


2016 ◽  
Vol 13 (11) ◽  
pp. 1503-1512 ◽  
Author(s):  
Arshad Mahmood ◽  
Felix Prüfert ◽  
Nuri Ari Efiana ◽  
Muhammad Imtiaz Ashraf ◽  
Martin Hermann ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 987
Author(s):  
Ülo Langel

In the most recent 25–30 years, multiple novel mechanisms and applications of cell-penetrating peptides (CPP) have been demonstrated, leading to novel drug delivery systems. In this review, I present a brief introduction to the CPP area with selected recent achievements. This is followed by a nostalgic journey into the research in my own laboratories, which lead to multiple CPPs, starting from transportan and paving a way to CPP-based therapeutic developments in the delivery of bio-functional materials, such as peptides, proteins, vaccines, oligonucleotides and small molecules, etc.


Author(s):  
G.E. Visscher ◽  
R. L. Robison ◽  
G. J. Argentieri

The use of various bioerodable polymers as drug delivery systems has gained considerable interest in recent years. Among some of the shapes used as delivery systems are films, rods and microcapsules. The work presented here will deal with the techniques we have utilized for the analysis of the tissue reaction to and actual biodegradation of injectable microcapsules. This work has utilized light microscopic (LM), transmission (TEM) and scanning (SEM) electron microscopic techniques. The design of our studies has utilized methodology that would; 1. best characterize the actual degradation process without artifacts introduced by fixation procedures and 2. allow for reproducible results.In our studies, the gastrocnemius muscle of the rat was chosen as the injection site. Prior to the injection of microcapsules the skin above the sites was shaved and tattooed for later recognition and recovery. 1.0 cc syringes were loaded with the desired quantity of microcapsules and the vehicle (0.5% hydroxypropylmethycellulose) drawn up. The syringes were agitated to suspend the microcapsules in the injection vehicle.


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