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Pharmaceutics
Special Issues
Biomedical Applications of Bioactive Cell Penetrating Peptides and Development of...
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Biomedical Applications of Bioactive Cell Penetrating Peptides and Development of Novel Biologics

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

Deadline for manuscript submissions: 30 September 2024 | Viewed by 1956

Special Issue Editors

Prof. Dr. John Howl

E-Mail Website
Guest Editor
Faculty of Health, Education and Life Sciences, City South Campus, SCT106, Birmingham City University, Westbourne Road, Edgbaston B15 3TN, UK
Interests: peptide synthesis; bioportide; stem cell; sperm physiology; cell signalling; receptors
Dr. Sarah Jones

E-Mail Website
Guest Editor
Research Institute in Healthcare Science, Faculty of Science & Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton WV1 1LY, UK
Interests: cell penetrating peptides; bioportides; stem cell biology; sperm physiology; mast cell degranulation

Special Issue Information

Dear Colleagues,

We are particularly honored to invite you to participate in this Special Issue of Pharmaceutics. The scope of this project is defined by accelerated numbers of studies that utilize cell penetrating peptides (CPPs) to achieve effective intracellular delivery of otherwise impermeable agents. As pharmacokinetic modifiers, CPPs convey bioactive agents (peptides, proteins, drug, antibodies, nucleotides, etc.) into intracellular compartments to influence eukaryotic cell biology as novel biologics. The recent FDA endorsement of a CPP/toxin formulation further predicts a promising future for CPPs as both therapeutic and diagnostic agents. This is clearly an exciting developmental period for CPPs in their many guises as the importance of this novel class of synthetic peptide attracts enhanced recognition.

The aim of this Special Issue is to provide impetus to the development of CPP technologies within a biomedical context and provide full coverage of contemporary developments by exploring topics including CPP design and bioengineering, cargo conjugation, modulation of protein–protein interactions and target-specific delivery in vivo. Full details of research methodologies will serve as a reference source to accelerate progress within the field.

For this Special Issue, both original research articles and reviews are welcome. Research areas may include, but are not limited to, the following topics:  selection and design of CPPs, transition of CPPs towards a clinical setting, mechanistic studies of CPPs in eukaryotic cells, therapeutic applications of CPPs for cardiovascular disease and cancer and intracellular targeting of CPP conjugates.

We look forward to receiving your contributions.

Prof. Dr. John Howl
Dr. Sarah Jones
Guest Editors

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

  • cell penetrating peptide
  • drug delivery
  • peptide synthesis
  • cancer
  • cardiovascular system
  • cell signalling
  • stem cell
  • bioportides
  • siRNA

Published Papers (1 paper)

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Research

19 pages, 2786 KiB  
Article
Toxicity Studies of Cardiac-Targeting Peptide Reveal a Robust Safety Profile
by Daniella A. Sahagun, Jack B. Lopuszynski, Kyle S. Feldman, Nicholas Pogodzinski and Maliha Zahid
Pharmaceutics 2024, 16(1), 73; https://doi.org/10.3390/pharmaceutics16010073 - 4 Jan 2024
Viewed by 1609
Abstract
Targeted delivery of therapeutics specifically to cardiomyocytes would open up new frontiers for common conditions like heart failure. Our prior work using a phage display methodology identified a 12-amino-acid-long peptide that selectively targets cardiomyocytes after an intravenous injection in as little as 5 [...] Read more.
Targeted delivery of therapeutics specifically to cardiomyocytes would open up new frontiers for common conditions like heart failure. Our prior work using a phage display methodology identified a 12-amino-acid-long peptide that selectively targets cardiomyocytes after an intravenous injection in as little as 5 min and was hence termed a cardiac-targeting peptide (CTP: APHLSSQYSRT). CTP has been used to deliver imaging agents, small drug molecules, photosensitizing nanoparticles, exosomes, and even miRNA to cardiomyocytes. As a natural extension to the development of CTP as a clinically viable cardiac vector, we now present toxicity studies performed with the peptide. In vitro viability studies were performed in a human left ventricular myocyte cell line with 10 µM of Cyanine-5.5-labeled CTP (CTP-Cy5.5). In vitro ion channel profiles were completed for CTP followed by extensive studies in stably transfected cell lines for several GPCR-coupled receptors. Positive data for GPCR-coupled receptors were interrogated further with RT-qPCRs performed on mouse heart tissue. In vivo studies consisted of pre- and post-blood pressure monitoring acutely after a single CTP (10 mg/Kg) injection. Further in vivo toxicity studies consisted of injecting CTP (150 µg/Kg) in 60, 6-week-old, wild-type CD1, male/female mice (1:1), with cohorts of mice euthanized on days 0, 1, 2, 7, and 14 with inhalational CO2, followed by blood collection via cardiac puncture, complete blood count analysis, metabolic profiling, and finally, liver, renal, and thyroid studies. Lastly, mouse cardiac MRI was performed immediately before and after CTP (150 µg/Kg) injection to assess changes in cardiac size or function. Human left ventricular cardiomyocytes showed no decrease in viability after a 30 min incubation with CTP-Cy5.5. No significant activation or inhibition of any of seventy-eight protein channels was observed other than OPRM1 and COX2 at the highest tested concentration, neither of which were expressed in mouse heart tissue as assessed using RT-qPCR. CTP (10 mg/Kg) injections led to no change in blood pressure. Blood counts and chemistries showed no evidence of significant hematological, hepatic, or renal toxicities. Lastly, there was no difference in cardiac function, size, or mass acutely in response to CTP injections. Our studies with CTP showed no activation or inhibition of GPCR-associated receptors in vitro. We found no signals indicative of toxicity in vivo. Most importantly, cardiac functions remained unchanged acutely in response to CTP uptake. Further studies using good laboratory practices are needed with prolonged, chronic administration of CTP conjugated to a specific cargo of choice before human studies can be contemplated. Full article
(This article belongs to the Special Issue Biomedical Applications of Bioactive Cell Penetrating Peptides and Development of Novel Biologics)
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