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Intelligent Nanomaterials for Medicine: Carrier Platforms and Targeting Strategies—State of the Art
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
Georgette B. Salieb-Beugelaar, Marc Wolf, Roman Lehner, Kegang Liu, Stephan Marsch, Patrick Hunziker
More than 20 years ago, Frankel and Pabo found that the trans-activating transcriptional activator (TAT) protein of HIV-1 is able to cross mammalian cell membranes and translocate into the nucleus [182]. A few years later, Prochiantz et al. reported the same effect for the Drosophila melanogaster Antennapedia homeodomain [183]. It was found that a short sequence of 10–16 amino acids was responsible for translocation. Based on this discovery, numerous cell-penetrating peptides (CPPs) have been developed for potential delivery of various biomolecules such as oligonucleotides, DNA, RNA, proteins, peptides, and drugs. A review on CPP and tumor-targeting peptides appeared recently [184]. CPPs are typically cationic (Tat, penetratin) or amphiphatic peptides of less than 30 amino acids showing lack of toxicity and can be grouped into two major classes comprising covalent linkage and non-covalent complexation with cargo molecules [185]. Cationic CPPs are generally composed of positively charged amino acids as arginine, lysine, and histidine, whereas amphiphatic CPPs are made up of lipophilic and hydrophilic parts [186]. Cellular uptake can occur through endocytotic (clathrin dependent, macropinocytosis, via caveola) or non-endocytotic pathways although mechanisms are not fully elucidated.
Chemical Modulation of Topical and Transdermal Permeation
Published in Marc B. Brown, Adrian C. Williams, The Art and Science of Dermal Formulation Development, 2019
Marc B. Brown, Adrian C. Williams
Cell-penetrating peptides were first reported in 1988 when it was found that the Trans-Activator of Transcription (TAT) protein from the human immunodeficiency virus 1 (HIV-1) entered tissue-cultured cells and promoted viral gene expression. Subsequently, numerous peptides showing similar cell-penetrating capacities have been discovered or, in some cases, rationally designed. Typically, cell-penetrating peptides are relatively short (up to ~30 residues) and can cross varied cell membranes with little or no toxicity using energy-dependent and/or independent mechanisms. Commonly, they carry multiple positively charged amino acids such as arginine or lysine – often termed polycationic – or have a sequence of alternating charged and non-polar amino acids.
Liquid Crystals as Drug Delivery Systems for Skin Applications
Published in Andreia Ascenso, Sandra Simões, Helena Ribeiro, Carrier-Mediated Dermal Delivery, 2017
Another interesting feature of liquid crystalline systems regarding skin drug delivery is that some commonly used lipid components, such as GMO and PT, are recognized as permeation enhancers. Thus, the lipid that comprises the lipid domain of the liquid crystalline system can improve drug permeation when in contact with skin by increasing stratum corneum fluidity and extracting lipids. In addition to structural similarity with skin lipids, the presence of these lipids with permeation enhancer properties result in synergistic effects that improve the permeation of skin by the drug [9,10,20,32]. Liquid crystalline systems also allow the incorporation of others permeation enhancers, such as oleic acid or isopropyl myristate, which can be dissolved in the lipid domain of the liquid crystal structure. Oleic acid has been used as permeation enhancer in liquid crystalline systems for skin delivery of cyclosporine-A [20,31]. It is also possible to incorporate other substances with the aim of improvement of drug permeation. Liquid crystalline drug delivery systems containing cell-penetrating peptides, such as penetratin, TAT, and RALA peptide, have been studied to enhance the penetration of nonsteroidal anti-inflammatory drugs (sodium diclofenac and celecoxib). Cell-penetrating peptides are a kind of peptides with functions of penetration into living cells that can be used to enhance delivery through skin in the development of drug delivery systems. They can overcome the stratum corneum barrier and improve drug permeation [41,47,48].
Improved transfer efficiency of supercharged 36 + GFP protein mediate nucleic acid delivery
Published in Drug Delivery, 2022
Lidan Wang, Jingping Geng, Linlin Chen, Xiangli Guo, Tao Wang, Yanfen Fang, Bonn Belingon, Jiao Wu, Manman Li, Ying Zhan, Wendou Shang, Yingying Wan, Xuemei Feng, Xianghui Li, Hu Wang
Cell penetrating peptides are short cationic peptides (examples include Tat (Wang et al., 2010; Wu et al., 2018) and Dot1l (Geng et al., 2020)), that facilitate cellular uptake of molecular cargoes (Kardani et al., 2019), including small chemical compounds (Uhl et al., 2020; Khan et al., 2021), peptides, proteins (Suresh et al., 2017), DNA/RNA (Shukla et al., 2014; Kato et al., 2016; Geng et al., 2021), nanoparticles (Berry, 2008), and liposomes (Liu et al., 2016). CPPs also have been proven to have the ability to deliver cargoes to pass biological barriers (like skin (Schutze-Redelmeier et al., 2004) and/or mucosal (Ji et al., 2017)), it is worth mentioning that several promising vaccine delivery systems based on CPPs have been developed. However, references suggested that the use of CPPs was often not sufficient for vaccine efficacy (Skwarczynski & Toth, 2019; Yang et al., 2019). Thus, this approach is still underdeveloped and require additional study.
Biotherapeutic effect of cell-penetrating peptides against microbial agents: a review
Published in Tissue Barriers, 2022
Idris Zubairu Sadiq, Aliyu Muhammad, Sanusi Bello Mada, Bashiru Ibrahim, Umar Aliyu Umar
Accordingly, CPP is set to resolve this challenge via facilitating the transport of therapeutic substances across membranes. The current resistance to antibiotics has necessitated the urgent need for alternatives from bioactive peptides, which have been shown to have the tremendous potential not only as antimicrobial agents but also as immune modulators, anti-cancer, and anti-inflammatory agents.8 The exploration of cell-penetrating peptides that display the characteristics of macromolecular vector carriers and viral vector enhancers has opened up new possibilities for biologically active cargo transport, along with therapeutic targets key genes, to different cells and tissues.9 In this review, attempts have been made to provide a critical appraisal on the classifications, cellular and molecular mechanism of action as well as the biotherapeutic applications of cell-penetrating peptides.
An overview of rational design of mRNA-based therapeutics and vaccines
Published in Expert Opinion on Drug Discovery, 2021
Kenneth K.W. To, William C.S. Cho
The high molecular weight and negative charge of mRNA species prevent their penetration of cell membrane through diffusion and also results in electrostatic repulsion from the anionic cell membrane. While the physical methods (e.g. electroporation) are widely used for delivering DNA-based drugs into the cells, the use of physical methods for intracellular mRNA drug delivery is less reported [107]. Cell penetrating peptides, which are cationic in nature, have been used to facilitate mRNA delivery to intracellular target sites. Protamine is an ariginine-rich cationic peptide that can bind to mRNA and transport it to the cytoplasm [108]. Recently, an innovative mRNA delivery platform has been reported, which consists of poly(lactic acid) and cationic cell penetrating peptides as mRNA condensing agent [109]. This novel mRNA-delivering nano-complexes were taken up efficiently by dendritic cells and they induced strong protein expression and innate immune response [109].