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Pharmaceutics
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Advances in Delivering Protein and Peptide Therapeutics, 2nd Edition
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Advances in Delivering Protein and Peptide Therapeutics, 2nd Edition

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

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 3335

Special Issue Editors

Dr. Ivan Guryanov

E-Mail Website
Guest Editor
1. Fresenius Kabi iPSUM, 23 Via San Leonardo, 45010 Villadose, RO, Italy
2. Institute of Chemistry, Saint-Petersburg State University, 26 Universitetsky Pr., 198504 St. Petersburg, Russia
Interests: synthesis of peptides and polyaminoacids for physicochemical and biomedical applications; gold nanoparticle functionalization; nanoparticle based drug delivery systems
Special Issues, Collections and Topics in MDPI journals
Dr. Evgenia G. Korzhikova-Vlakh

E-Mail Website
Guest Editor
1. Institute of Macromolecular Compounds, Russian Academy of Sciences, 199004 Saint-Petersburg, Russia
2. Institute of Chemistry, Saint-Petersburg State University, Universitetsky pr. 26, 198504 St. Petersburg, Russia
Interests: amphiphilic polymers; self-assembling; nanoparticles; biodegradation; drug delivery systems; proteins; peptides; DNA/RNA
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent achievements in peptide and protein synthesis and large-scale production have revealed the high potential of these compounds as selective and efficient drugs for the treatment of a number of diseases. Currently, proteins and peptides are widely considered as prospective biopharmaceutics or vaccines and many of them are already available in clinics as oral, intravenous, subcutaneous, transdermal, and intranasal formulations. In spite of the many advantages of peptides and proteins as drugs, their wide application is limited because of some crucial obstacles. Among these, opsonization and proteolytic degradation severely affect their therapeutic efficiency. In turn, more frequent administration may cause many complications and undesirable side-effects. Moreover, the intracellular action of some peptide and protein drugs can be limited because of their poor penetration into the cell. The abovementioned problems can be overcome by different approaches, such as conjugation of peptides/proteins with polymers, encapsulation/entrapment of biopharmaceutics into polymer particles, as well as application of special systems or/and vectors for intracellular delivery.

As Guest Editors, we invite researchers to submit to this Special Issue their valuable results and findings focused on conjugation, encapsulation, entrapment, preparation of novel formulations, or other modifications to enhance stability of peptides/proteins and improve their therapeutic efficacy or intracellular delivery. Articles prepared as research papers, reviews, or short communications are welcomed for publication.

Dr. Ivan Guryanov
Dr. Evgenia G. Korzhikova-Vlakh
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

  • peptides
  • proteins
  • delivery systems
  • conjugation
  • encapsulation
  • entrapment
  • novel formulations
  • intracellular delivery
  • oral delivery
  • parenteral delivery
  • nasal delivery
  • transdermal delivery
  • ocular delivery

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Published Papers (3 papers)

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Research

22 pages, 3295 KiB  
Article
Poly(2-Deoxy-2-Methacrylamido-D-Glucose)-Based Complex Conjugates of Colistin, Deferoxamine and Vitamin B12: Synthesis and Biological Evaluation
by Mariia Stepanova, Mariia Levit, Tatiana Egorova, Yulia Nashchekina, Tatiana Sall, Elena Demyanova, Ivan Guryanov and Evgenia Korzhikova-Vlakh
Pharmaceutics 2024, 16(8), 1080; https://doi.org/10.3390/pharmaceutics16081080 - 17 Aug 2024
Viewed by 474
Abstract
Growing resistance to traditional antibiotics poses a global threat to public health. In this regard, modification of known antibiotics, but with limited applications due to side effects, is one of the extremely promising approaches at present. In this study, we proposed the synthesis [...] Read more.
Growing resistance to traditional antibiotics poses a global threat to public health. In this regard, modification of known antibiotics, but with limited applications due to side effects, is one of the extremely promising approaches at present. In this study, we proposed the synthesis of novel complex polymeric conjugates of the peptide antibiotic colistin (CT). A biocompatible and water-soluble synthetic glycopolymer, namely, poly(2-deoxy-2-methacrylamido-D-glucose) (PMAG), was used as a polymer carrier. In addition to monoconjugates containing CT linked to PMAG by hydrolyzable and stable bonds, a set of complex conjugates also containing the siderophore deferoxamine (DFOA) and vitamin B12 was developed. The structures of the conjugates were confirmed by 1H NMR and FTIR-spectroscopy, while the compositions of conjugates were determined by UV–Vis spectrophotometry and HPLC analysis. The buffer media with pH 7.4, corresponding to blood or ileum pH, and 5.2, corresponding to the intestinal pH after ingestion or pH in the focus of inflammation, were used to study the release of CT. The resulting conjugates were examined for cytotoxicity and antimicrobial activity. All conjugates showed less cytotoxicity than free colistin. A Caco-2 cell permeability assay was carried out for complex conjugates to simulate the drug absorption in the intestine. In contrast to free CT, which showed very low permeability through the Caco-2 monolayer, the complex polymeric conjugates of vitamin B12 and CT provided significant transport. The antimicrobial activity of the conjugates depended on the conjugate composition. It was found that conjugates containing CT linked to the polymer by a hydrolyzable bond were found to be more active than conjugates with a non-hydrolyzable bond between CT and PMAG. Conjugates containing DFOA complexed with Fe3+ were characterized by enhanced antimicrobial activity against Pseudomonas aeruginosa compared to other conjugates. Full article
(This article belongs to the Special Issue Advances in Delivering Protein and Peptide Therapeutics, 2nd Edition)
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15 pages, 4235 KiB  
Article
Intranasal Delivery of Cell-Penetrating Therapeutic Peptide Enhances Brain Delivery, Reduces Inflammation, and Improves Neurologic Function in Moderate Traumatic Brain Injury
by Yaswanthi Yanamadala, Ritika Roy, Afrika Alake Williams, Navya Uppu, Audrey Yoonsun Kim, Mark A. DeCoster, Paul Kim and Teresa Ann Murray
Pharmaceutics 2024, 16(6), 774; https://doi.org/10.3390/pharmaceutics16060774 - 7 Jun 2024
Viewed by 972
Abstract
Following traumatic brain injury (TBI), secondary brain damage due to chronic inflammation is the most predominant cause of the delayed onset of mood and memory disorders. Currently no therapeutic approach is available to effectively mitigate secondary brain injury after TBI. One reason is [...] Read more.
Following traumatic brain injury (TBI), secondary brain damage due to chronic inflammation is the most predominant cause of the delayed onset of mood and memory disorders. Currently no therapeutic approach is available to effectively mitigate secondary brain injury after TBI. One reason is the blood–brain barrier (BBB), which prevents the passage of most therapeutic agents into the brain. Peptides have been among the leading candidates for CNS therapy due to their low immunogenicity and toxicity, bioavailability, and ease of modification. In this study, we demonstrated that non-invasive intranasal (IN) administration of KAFAK, a cell penetrating anti-inflammatory peptide, traversed the BBB in a murine model of diffuse, moderate TBI. Notably, KAFAK treatment reduced the production of proinflammatory cytokines that contribute to secondary injury. Furthermore, behavioral tests showed improved or restored neurological, memory, and locomotor performance after TBI in KAFAK-treated mice. This study demonstrates KAFAK’s ability to cross the blood–brain barrier, to lower proinflammatory cytokines in vivo, and to restore function after a moderate TBI. Full article
(This article belongs to the Special Issue Advances in Delivering Protein and Peptide Therapeutics, 2nd Edition)
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18 pages, 7262 KiB  
Article
QbD Approach-Based Preparation and Optimization of Hydrophobic Ion-Pairing Complex of Lysozyme with Sodium Dodecyl Sulphate to Enhance Stability in Lipid-Based Carriers
by Alharith A. A. Hassan, Tamás Sovány, Krisztián Pamlényi, Martin Deák, Viktória Hornok, Edit Csapó, Géza Regdon, Jr., Ildikó Csóka and Katalin Kristó
Pharmaceutics 2024, 16(5), 589; https://doi.org/10.3390/pharmaceutics16050589 - 26 Apr 2024
Viewed by 1100
Abstract
Hydrophobic ion pairing (HIP) complexation was found to be an efficient approach in modulating the release and enhancing the stability and encapsulation of hydrophilic macromolecules such as proteins in hydrophobic nano/microcarriers. The present work strives to develop and optimize the preparation of the [...] Read more.
Hydrophobic ion pairing (HIP) complexation was found to be an efficient approach in modulating the release and enhancing the stability and encapsulation of hydrophilic macromolecules such as proteins in hydrophobic nano/microcarriers. The present work strives to develop and optimize the preparation of the HIP complex of the antimicrobial enzyme lysozyme (LYZ) with the ion-pairing agent (IPA) sodium dodecyl sulphate (SDS) relying on the quality-by-design (QbD) approach. The quality target product profile (QTPP) includes the achievement of maximal lipophilicity in a reversible manner to enable the maintenance of biological activity. The related critical quality attributes (CQAs) were defined as complexation efficacy, complex stability, enzyme recovery and activity. Three risk assessment (RA) tools were used to identify and rank the critical process parameters (CPPs) and critical material attributes (CMAs). From this assessment, the pH of the medium, LYZ:SDS molar ratio and drying conditions were determined as high-risk factors that need to be investigated. To the best of our knowledge, for the first time, electrostatic titration was used as a smart approach to determine the optimum molar ratio at different pH values. Based on the predefined CQAs, pH 8 with an LYZ/SDS molar ratio of 1:8 was found to be the optimal condition for complexation efficiency and recovery (%) of a biologically active enzyme. A cost-effective drying process based on a ventilated oven was developed, which resulted in complex qualities comparable to those obtained by the commonly used freeze-drying method. In a nutshell, the optimum conditions for the preparation of the LYZ/SDS HIP complex were efficiently facilitated by the rational application of QbD principles and the utilization of efficient electrostatic titration and ventilated oven-drying methods. Full article
(This article belongs to the Special Issue Advances in Delivering Protein and Peptide Therapeutics, 2nd Edition)
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