Next-Generation Delivery Systems for Peptides, Proteins, and Nucleic Acids

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

Deadline for manuscript submissions: 31 May 2026 | Viewed by 773

Special Issue Editor


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Guest Editor
Academy of Pharmacy, Xi’an Jiaotong-Liverpool University, Suzhou, China
Interests: pharmaceutical sciences; drug delivery systems; nanotechnology in pharmaceuticals; oral antibiotic formulations; controlled release; pharmacognosy; nanomaterials; biopharmaceutics

Special Issue Information

Dear Colleagues,

The rapid growth of biologics, such as peptides, proteins, and nucleic acids, has revolutionized modern therapeutics, offering highly specific and potent treatment options for a wide range of diseases. However, their clinical translation remains limited by challenges in stability, permeability and targeted delivery. This Special Issue, Next-Generation Delivery Systems for Peptides, Proteins, and Nucleic Acids, aims to highlight recent advances in innovative delivery technologies designed to overcome these barriers. It welcomes research and review articles focusing on nanocarriers, hydrogels, lipid- and polymer-based systems, micro/nano fabrication and bioinspired delivery strategies that enhance the efficacy, stability and controlled release of biomacromolecules. The Issue seeks to provide a comprehensive platform for interdisciplinary insights at the interface of pharmaceutics, materials science and molecular biology, accelerating the development of next-generation biotherapeutics.

Dr. Aun Raza
Guest Editor

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Keywords

  • drug delivery systems
  • peptide delivery
  • protein therapeutics
  • nucleic acid delivery
  • nanocarriers
  • biomaterials
  • controlled release
  • targeted delivery
  • gene therapy
  • biopharmaceutics

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Published Papers (1 paper)

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Research

23 pages, 5105 KB  
Article
Thioester-Containing Ionizable Lipids with Enhanced Endosomal Escape and Biodegradability for mRNA and tRNA Delivery
by Álvaro Peña, Esther Broset, Enrique Lucia, Laura García-Latorre, Víctor Navarro, Carlos Matute, Ana Gallego-Lleyda, Teresa Alejo, Eduardo Romanos, Alba García, Juan Martínez-Oliván and Javier Giménez-Warren
Pharmaceutics 2026, 18(4), 472; https://doi.org/10.3390/pharmaceutics18040472 - 13 Apr 2026
Viewed by 495
Abstract
Background/Objectives: Lipid nanoparticles (LNPs) containing ionizable lipids represent the most advanced non-viral delivery vehicles and have become state-of-the-art carriers for RNA therapeutics. However, further improvements in endosomal escape efficiency and biodegradability are still needed, especially for nucleic acids with transient activity such [...] Read more.
Background/Objectives: Lipid nanoparticles (LNPs) containing ionizable lipids represent the most advanced non-viral delivery vehicles and have become state-of-the-art carriers for RNA therapeutics. However, further improvements in endosomal escape efficiency and biodegradability are still needed, especially for nucleic acids with transient activity such as messenger RNA (mRNA) and transfer RNA (tRNA). Methods: In this study, a novel library of highly biodegradable ionizable lipids featuring thioester groups within the linker region was designed and synthesized, thereby expanding the chemical linker toolbox for future ionizable lipid development. Results: Comprehensive in vivo structure–activity relationship studies led to the identification of CP-LC-1272 as a lead candidate that markedly enhances endosomal escape and exhibits superior in vivo biodegradability, attributed to the high acid-lability of thioester bonds. LNPs containing CP-LC-1272 maintained in vivo activity after six months of storage in lyophilized form and demonstrated superior in vivo efficiency compared to SM-102 in mRNA expression studies, as well as similar protein restoration in a tRNA delivery model targeting premature stop-codon mutations. Conclusions: The rapid biodegradability of these thioester-activated ionizable lipids (TAILs) suggests a reduced risk of accumulation, with the potential to enable safe repeated dosing or high-dosage RNA therapies, positioning TAILs as a versatile and safe platform for next-generation RNA therapeutics. Full article
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