Drug Delivery System with Cell-Penetrating Peptides/Nano-Materials

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (20 March 2024) | Viewed by 10596

Special Issue Editor

Department of Laboratory Medicine and Biotechnology, College of Medicine, Tzu Chi University, Hualien 970374, Taiwan
Interests: peptide-based drug delivery systems; nanomaterials; molecular biology; microbiology

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to the new Special Issue, Drug Delivery Systems with Cell-Penetrating Peptides/Nano-Materials. The developments and studies of drug delivery systems have flourished in recent decades. Among these studies, natural sources and biodegradability are of great concern in drug delivery systems. Cell-penetrating peptides are a class of short peptides with the ability to carry molecules; they act as shuttles and serve as peptide-based drug delivery systems. Nano-materials combined with cell-penetrating peptides can form nano-scale complexes and penetrate cells as well as tissues easily because of their small size. Therapeutic and functional cell-penetrating peptides/nano-materials displaying potent drug delivery, comprehensive penetration, and efficient biodegradability reduce side effects and potential body accumulations. Drug delivery systems with cell-penetrating peptides/nano-materials are current trends in the pharmacological sciences. However, a broad spectrum of penetration in cells or tissues decreases the applications in specific targets. Studies on control release are emergent in research on cell-penetrating peptide/nano-material-based drug delivery systems.

This Special Issue aims to gather and disseminate the latest advancements, perspectives, and trends in cell-penetrating peptide/nano-material-based drug delivery systems. In this Special Issue, original research articles, short communications, and reviews are welcome. Research areas may include (but are not limited to) the following: newly designed cell-penetrating peptides, pharmaceutical applications of peptide-based drug delivery, cell-penetrating-peptide-mediated DNA/RNA delivery in gene therapy and biotechnology, nanoparticle-loaded devices in peptide-based drug delivery, control release design in delivery systems, medicines with cell-penetrating peptides/nano-materials enhancements, and cell-penetrating peptides/nano-materials-mediated transformations in microenvironments.

I look forward to receiving your contributions.

Dr. Betty Revon Liu
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • peptide-based drug delivery systems
  • nano-materials
  • nano-scale complex formations
  • gene/nucleotide deliveries
  • drug-loaded nano-devices
  • targeting and controlled-release systems

Published Papers (6 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

20 pages, 4229 KiB  
Article
Amphipathic Cell-Penetrating Peptide-Aided Delivery of Cas9 RNP for In Vitro Gene Editing and Correction
by Mert Öktem, Enrico Mastrobattista and Olivier G. de Jong
Pharmaceutics 2023, 15(10), 2500; https://doi.org/10.3390/pharmaceutics15102500 - 20 Oct 2023
Cited by 1 | Viewed by 1773
Abstract
The therapeutic potential of the CRISPR-Cas9 gene editing system in treating numerous genetic disorders is immense. To fully realize this potential, it is crucial to achieve safe and efficient delivery of CRISPR-Cas9 components into the nuclei of target cells. In this study, we [...] Read more.
The therapeutic potential of the CRISPR-Cas9 gene editing system in treating numerous genetic disorders is immense. To fully realize this potential, it is crucial to achieve safe and efficient delivery of CRISPR-Cas9 components into the nuclei of target cells. In this study, we investigated the applicability of the amphipathic cell-penetrating peptide LAH5, previously employed for DNA delivery, in the intracellular delivery of spCas9:sgRNA ribonucleoprotein (RNP) and the RNP/single-stranded homology-directed repair (HDR) template. Our findings reveal that the LAH5 peptide effectively formed nanocomplexes with both RNP and RNP/HDR cargo, and these nanocomplexes demonstrated successful cellular uptake and cargo delivery. The loading of all RNP/HDR components into LAH5 nanocomplexes was confirmed using an electrophoretic mobility shift assay. Functional screening of various ratios of peptide/RNP nanocomplexes was performed on fluorescent reporter cell lines to assess gene editing and HDR-mediated gene correction. Moreover, targeted gene editing of the CCR5 gene was successfully demonstrated across diverse cell lines. This LAH5-based delivery strategy represents a significant advancement toward the development of therapeutic delivery systems for CRISPR-Cas-based genetic engineering in in vitro and ex vivo applications. Full article
(This article belongs to the Special Issue Drug Delivery System with Cell-Penetrating Peptides/Nano-Materials)
Show Figures

Figure 1

15 pages, 4511 KiB  
Article
Enhancing Cell Penetration Efficiency of Cyclic Oligoarginines Using Rigid Scaffolds
by Csaba Bató, Ildikó Szabó and Zoltán Bánóczi
Pharmaceutics 2023, 15(6), 1736; https://doi.org/10.3390/pharmaceutics15061736 - 14 Jun 2023
Cited by 2 | Viewed by 846
Abstract
Delivering therapeutic agents into cells has always been a major challenge. In recent years, cyclization emerged as a tool for designing CPPs to increase their internalization and stability. Cyclic ring(s) can protect the peptide from enzymatic degradation, so cyclic peptides remain intact. Therefore [...] Read more.
Delivering therapeutic agents into cells has always been a major challenge. In recent years, cyclization emerged as a tool for designing CPPs to increase their internalization and stability. Cyclic ring(s) can protect the peptide from enzymatic degradation, so cyclic peptides remain intact. Therefore they can be good carrier molecules. In this work, the preparation and investigation of efficient cyclic CPPs are described. Different oligoarginines were designed to conjugate with rigid aromatic scaffolds or form disulfide bonds. The reaction between the scaffolds and the peptides forms stable thioether bonds, constraining the peptide into a cyclic structure. The constructs presented very efficient internalization on cancerous cell lines. Our peptides use more than one endocytic pathway for cellular uptake. In this way, short peptides, which can compete with the penetration of well-known CPPs such as octaarginine (Arg8), may be synthesized through cyclization. Full article
(This article belongs to the Special Issue Drug Delivery System with Cell-Penetrating Peptides/Nano-Materials)
Show Figures

Figure 1

34 pages, 18003 KiB  
Article
Polymeric Micelles Formulation of Combretastatin Derivatives with Enhanced Solubility, Cytostatic Activity and Selectivity against Cancer Cells
by Igor D. Zlotnikov, Alexander A. Ezhov, Artem S. Ferberg, Sergey S. Krylov, Marina N. Semenova, Victor V. Semenov and Elena V. Kudryashova
Pharmaceutics 2023, 15(6), 1613; https://doi.org/10.3390/pharmaceutics15061613 - 29 May 2023
Cited by 10 | Viewed by 1424
Abstract
Combretastatin derivatives is a promising class of antitumor agents, tubulin assembly inhibitors. However, due to poor solubility and insufficient selectivity to tumor cells, we believe, their therapeutic potential has not been fully realized yet. This paper describes polymeric micelles based on chitosan (a [...] Read more.
Combretastatin derivatives is a promising class of antitumor agents, tubulin assembly inhibitors. However, due to poor solubility and insufficient selectivity to tumor cells, we believe, their therapeutic potential has not been fully realized yet. This paper describes polymeric micelles based on chitosan (a polycation that causes pH and thermosensitivity of micelles) and fatty acids (stearic, lipoic, oleic and mercaptoundecanoic), which were used as a carrier for a range of combretastatin derivatives and reference organic compounds, demonstrating otherwise impossible delivery to tumor cells, at the same time substantially reduced penetration into normal cells. Polymers containing sulfur atoms in hydrophobic tails form micelles with a zeta potential of about 30 mV, which increases to 40–45 mV when cytostatics are loaded. Polymers with tails of oleic and stearic acids form poorly charged micelles. The use of polymeric 400 nm micelles provides the dissolution of hydrophobic potential drug molecules. Micelles could significantly increase the selectivity of cytostatics against tumors, which has been shown using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, Fourier transform infrared (FTIR) spectroscopy, flow cytometry and fluorescence microscopy. Atomic force microscopy presented the difference between the unloaded micelles and those loaded with the drug: the size of the former was 30 nm on average, while the latter had a “disc-like” shape and a size of about 450 nm. The loading of drugs into the core of micelles was confirmed by UV and fluorescence spectroscopy methods; shifts of absorption and emission maxima into the long-wavelength region by tens of nm was observed. With FTIR spectroscopy, a high interaction efficiency of micelles with the drug on cells was demonstrated, but at the same time, selective absorption was observed: micellar cytostatics penetrate into A549 cancer cells 1.5–2 times better than the simple form of the drugs. Moreover, in normal HEK293T, the penetration of the drug is reduced. The proposed mechanism for reducing the accumulation of drugs in normal cells is the adsorption of micelles on the cell surface and the preservation of cytostatics to penetrate inside the cells. At the same time, in cancer cells, due to the structural features of the micelles, they penetrate inside, merging with the membrane and releasing the drug by pH- and glutathione-sensitive mechanisms. From a methodological point of view, we have proposed a powerful approach to the observation of micelles using a flow cytometer, which, in addition, allows us to quantify the cells that have absorbed/adsorbed cytostatic fluorophore and distinguish between specific and non-specific binding. Thus, we present polymeric micelles as drug delivery systems in tumors using the example of combretastatin derivatives and model fluorophore-cytostatic rhodamine 6G. Full article
(This article belongs to the Special Issue Drug Delivery System with Cell-Penetrating Peptides/Nano-Materials)
Show Figures

Figure 1

15 pages, 6111 KiB  
Article
Antioxidant Efficacy of Green-Synthesized Silver Nanoparticles Promotes Wound Healing in Mice
by Vajravathi Lakkim, Madhava C. Reddy, VijayaDurga V. V. Lekkala, Veeranjaneya Reddy Lebaka, Mallikarjuna Korivi and Dakshayani Lomada
Pharmaceutics 2023, 15(5), 1517; https://doi.org/10.3390/pharmaceutics15051517 - 17 May 2023
Cited by 1 | Viewed by 1536
Abstract
Developing an efficient and cost-effective wound-healing substance to treat wounds and regenerate skin is desperately needed in the current world. Antioxidant substances are gaining interest in wound healing, and green-synthesized silver nanoparticles have drawn considerable attention in biomedical applications due to their efficient, [...] Read more.
Developing an efficient and cost-effective wound-healing substance to treat wounds and regenerate skin is desperately needed in the current world. Antioxidant substances are gaining interest in wound healing, and green-synthesized silver nanoparticles have drawn considerable attention in biomedical applications due to their efficient, cost-effective, and non-toxic nature. The present study evaluated in vivo wound healing and antioxidant activities of silver nanoparticles from Azadirachta indica (AAgNPs) and Catharanthus roseus (CAgNPs) leaf extracts in BALB/c mice. We found rapid wound healing, higher collagen deposition, and increased DNA and protein content in AAgNPs- and CAgNPs (1% w/w)-treated wounds than in control and vehicle control wounds. Skin antioxidant enzyme activities (SOD, catalase, GPx, GR) were significantly (p < 0.05) increased after 11 days CAgNPs and AAgNPs treatment. Furthermore, the topical application of CAgNPs and AAgNPs tends to suppress lipid peroxidation in wounded skin samples. Histopathological images evidenced decreased scar width, epithelium restoration, fine collagen deposition, and fewer inflammatory cells in CAgNPs and AAgNPs applied wounds. In vitro, the free radical scavenging activity of CAgNPs and AAgNPs was demonstrated by DPPH and ABTS radical scavenging assays. Our findings suggest that silver nanoparticles prepared from C. roseus and A. indica leaf extracts increased antioxidant status and improved the wound-healing process in mice. Therefore, these silver nanoparticles could be potential natural antioxidants to treat wounds. Full article
(This article belongs to the Special Issue Drug Delivery System with Cell-Penetrating Peptides/Nano-Materials)
Show Figures

Figure 1

24 pages, 5772 KiB  
Article
Differential Blood–Brain Barrier Transport and Cell Uptake of Cyclic Peptides In Vivo and In Vitro
by Erik Melander, Camilla Eriksson, Sara Wellens, Kimia Hosseini, Robert Fredriksson, Fabien Gosselet, Maxime Culot, Ulf Göransson, Margareta Hammarlund-Udenaes and Irena Loryan
Pharmaceutics 2023, 15(5), 1507; https://doi.org/10.3390/pharmaceutics15051507 - 16 May 2023
Viewed by 1893
Abstract
The blood–brain barrier (BBB) poses major challenges to drug delivery to the CNS. SFTI-1 and kalata B1 are cyclic cell-penetrating peptides (cCPPs) with high potential to be used as scaffolds for drug delivery. We here studied their transport across the BBB and distribution [...] Read more.
The blood–brain barrier (BBB) poses major challenges to drug delivery to the CNS. SFTI-1 and kalata B1 are cyclic cell-penetrating peptides (cCPPs) with high potential to be used as scaffolds for drug delivery. We here studied their transport across the BBB and distribution within the brain to gauge the potential of these two cCPPs as scaffolds for CNS drugs. In a rat model, SFTI-1 exhibited, for a peptide, high extent of BBB transport with a partitioning of unbound SFTI-1 across the BBB, Kp,uu,brain, of 13%, while only 0.5% of kalata B1 equilibrated across the BBB. By contrast, kalata B1, but not SFTI-1, readily entered neural cells. SFTI-1, but not kalata B1, could be a potential CNS delivery scaffold for drugs directed to extracellular targets. These findings indicate that differences between the BBB transport and cellular uptake abilities of CPPs are crucial in the development of peptide scaffolds. Full article
(This article belongs to the Special Issue Drug Delivery System with Cell-Penetrating Peptides/Nano-Materials)
Show Figures

Figure 1

Review

Jump to: Research

45 pages, 9367 KiB  
Review
Challenges and Opportunities in the Oral Delivery of Recombinant Biologics
by Solene Masloh, Maxime Culot, Fabien Gosselet, Anne Chevrel, Leonardo Scapozza and Magali Zeisser Labouebe
Pharmaceutics 2023, 15(5), 1415; https://doi.org/10.3390/pharmaceutics15051415 - 05 May 2023
Cited by 3 | Viewed by 1936
Abstract
Recombinant biological molecules are at the cutting-edge of biomedical research thanks to the significant progress made in biotechnology and a better understanding of subcellular processes implicated in several diseases. Given their ability to induce a potent response, these molecules are becoming the drugs [...] Read more.
Recombinant biological molecules are at the cutting-edge of biomedical research thanks to the significant progress made in biotechnology and a better understanding of subcellular processes implicated in several diseases. Given their ability to induce a potent response, these molecules are becoming the drugs of choice for multiple pathologies. However, unlike conventional drugs which are mostly ingested, the majority of biologics are currently administered parenterally. Therefore, to improve their limited bioavailability when delivered orally, the scientific community has devoted tremendous efforts to develop accurate cell- and tissue-based models that allow for the determination of their capacity to cross the intestinal mucosa. Furthermore, several promising approaches have been imagined to enhance the intestinal permeability and stability of recombinant biological molecules. This review summarizes the main physiological barriers to the oral delivery of biologics. Several preclinical in vitro and ex vivo models currently used to assess permeability are also presented. Finally, the multiple strategies explored to address the challenges of administering biotherapeutics orally are described. Full article
(This article belongs to the Special Issue Drug Delivery System with Cell-Penetrating Peptides/Nano-Materials)
Show Figures

Figure 1

Back to TopTop