ArticleMolecular pharmaceutics
Conjugation with cationic cell-penetrating peptide increases pulmonary absorption of insulin.
Article in Molecular pharmaceutics. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 58 citations in OpenAlex.
- Integrative Peptide Drug Development: Chemical Engineering, AI-Driven Design, and Cell-Penetrating Peptides.Pharmaceutics · 2026Review
- Enhancing diabetes treatment by targeted nucleic acid and drug delivery using cell-penetrating peptides, peptide nucleic acids, and receptor targeting.Frontiers in pharmacology · 2026Review
- Preventing Protein Self-Association Through Strategic Covalent Modification.Journal of peptide science : an official publication of the European Peptide Society · 2025Article
- Nanoparticles with Cell-Penetrating Peptides for Oral Delivery: A Case for Oral Delivery of Insulin.International journal of nanomedicine · 2025Review
- Recent Advances of Cell-Penetrating Peptides and Their Application as Vectors for Delivery of Peptide and Protein-Based Cargo Molecules.Pharmaceutics · 2023Review
- Autophagy responsive intra-intercellular delivery nanoparticles for effective deep solid tumor penetration.Journal of nanobiotechnology · 2022Article
- Systemic and brain delivery of antidiabetic peptides through nasal administration using cell-penetrating peptides.Frontiers in pharmacology · 2022Review
- In Vitro and Ex Vivo Evaluation of Penetratin as a Non-invasive Permeation Enhancer in the Penetration of Salmon Calcitonin through TR146 Buccal Cells and Porcine Buccal Tissues.Pharmaceuticals (Basel, Switzerland) · 2020Article
- A review of lipidation in the development of advanced protein and peptide therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2019Review
- A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides.International journal of nanomedicine · 2017Article
- Photodynamic therapy by conjugation of cell-penetrating peptide with fluorochrome.International journal of nanomedicine · 2017Article
- Applications and Challenges for Use of Cell-Penetrating Peptides as Delivery Vectors for Peptide and Protein Cargos.International journal of molecular sciences · 2016Review
- Intracellular Delivery of Molecular Cargo Using Cell-Penetrating Peptides and the Combination Strategies.International journal of molecular sciences · 2015Review
- Utilization of Glycosaminoglycans/Proteoglycans as Carriers for Targeted Therapy Delivery.International journal of cell biology · 2015Review
- Enhanced cellular entry and efficacy of tat conjugates by rational design of the auxiliary segment.Molecular pharmaceutics · 2014Article
- Rapid lymph accumulation of polystyrene nanoparticles following pulmonary administration.Pharmaceutical research · 2013Article
- Cell-penetrating peptides as tools to enhance non-injectable delivery of biopharmaceuticals.Tissue barriersReview
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
In this study, we determined if cell-penetrating peptides (CPPs) can be used to enhance the absorption rate of insulin (INS) across the alveolar epithelial barrier. Using a heterobifunctional cross-linker, INS was conjugated to a series of cationic CPPs, including Tat peptide, oligoarginine (r9) or oligolysine (k9), via disulfide bridge to a D-isoform cysteine (c) present at the N-terminal of the peptide sequence, yielding INS-cTat, INS-cr9, and INS-ck9, respectively. SDS-PAGE and MALDI-TOF mass spectroscopy confirmed homogeneous conjugates with a 1:1 ratio of INS and various CPPs. Transport of INS and INS-CPPs across primary cultured rat alveolar epithelial cell monolayers was in the order INS-cr9 > INS-cTat > INS-ck9 > INS, with 27-, 19- and 4-fold increase compared to native INS, respectively. Transport of INS-cr9 was temperature- and time-dependent. Covalent conjugation between r9 and INS, as opposed to adding unconjugated INS and r9 together into donor fluid, was necessary to enhance transport of INS. Absorption of INS-cr9 across the alveolar epithelial barrier appeared to be in part transcellular, since INS-cr9 transport in the presence of heparin and protamine was decreased by approximately 20%. Adsorptive transcytosis appeared to be in part responsible for INS-cr9 absorption, as INS-cr9 did not compete with free INS in binding assays for INS receptors. Finally, intratracheal instillation of INS-cr9 in diabetic rats resulted in a steady decrease in blood glucose level that was more sustained over time when compared with INS. These results suggest that oligoarginine can be used to increase the alveolar absorption rate of insulin (and potentially other macromolecules as well).
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Registered trials
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