Molecular Investigation of SNAC as an Oral Peptide Permeation Enhancer in Lipid Membranes via Solid-State NMR DOI
Jing Ling,

Ryan Schroder,

W. Peter Wuelfing

et al.

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: 22(1), P. 459 - 473

Published: Dec. 17, 2024

Oral peptide therapeutics are increasingly favored in the pharmaceutical industry for their ease of use and better patient adherence. However, they face challenges with poor oral bioavailability due to high molecular weight surface polarity. Permeation enhancers (PEs) like salcaprozate sodium (SNAC) have shown promise clinical trials, achieving about 1% bioavailability. One proposed mechanism enhancing permeation is membrane perturbation or fluidization, though direct experimental proof quantitative analysis these effects still needed. This study employs solid-state NMR (ssNMR) investigate how SNAC interacts hydrated DMPC liposomes, measuring enhancements fluidity across interfacial transmembrane regions. The methodology involves analyzing phosphate lipid headgroups acyl chains using static

Language: Английский

Enhanced electrochemical CO2-to-ethylene conversion through second-shell coordination on a Cu single-atom catalyst DOI
Yi Shen, Yongliang Pan,

Huanyong Xiao

et al.

Journal of Materials Chemistry A, Journal Year: 2024, Volume and Issue: 12(15), P. 9075 - 9087

Published: Jan. 1, 2024

The electrocatalytic CO 2 reduction reaction (CO RR) utilizing Cu single-atom catalyst modulation through second-shell S coordination (Cu–C 3 N 4 –S) achieves predominant catalytic activity with high C H faradaic efficiency at low potentials.

Language: Английский

Citations

9
Physicochemical and structural insights into lyophilized mRNA-LNP from lyoprotectant and buffer screenings DOI
Yuchen Fan, Diamanda Rigas, Lee Joon Kim

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 373, P. 727 - 737

Published: Aug. 2, 2024

Language: Английский

Citations

7
Molecular Insight into Lipid Nanoparticle Assembly from NMR Spectroscopy and Molecular Dynamics Simulation DOI
Mingyue Li,

Ryan Schroder,

Umut Ozuguzel

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

Lipid nanoparticles (LNPs) have emerged as the premier drug delivery system for oligonucleotide vaccines and therapeutics in recent years. Despite their prosperous advancement research clinical applications, there is a significant lack of mechanistic understanding assembly lipid particles at molecular level. In our study, we utilized combination solution solid-state NMR, together with dynamics simulations, to elucidate local structures interactions chemical components across multiple motional regimes. Our results comprehensively evaluated impact formulation engineering process factors on particle formation identified interplay phospholipids (DSPC), poly(ethylene glycol) (PEG) conjugates, cholesterol governing size from structural perspective, using static 31P NMR techniques. These studies provide novel insights into properties LNP envelope membrane. Additionally, compositional distribution play critical role consequent stability potency. this intermolecular contacts among one-dimensional 1H-13C cross-polarization magic angle spinning experiments, 1H relaxation measurements, two-dimensional 1H-1H correlation methods, providing basis assembly. Interestingly, cationic ionizable lipids, conventionally regarded stabilizing agents primarily located within core LNPs, were found interact PEG lipids coexist outer layer particles. We suggest that LNPs examined here are comprised an rich surrounding region. high-resolution findings offer insightful dynamic details pertaining individual influence complex structure engineering.

Language: Английский

Citations

0
Industrial Horizons in Pharmaceutical Science DOI Creative Commons
Mark L. Brader, Hai‐Young Kim,

Otilia Koo

et al.

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: 21(9), P. 4183 - 4188

Published: May 29, 2024

ADVERTISEMENT RETURN TO ARTICLES ASAPPREVEditorialNEXTIndustrial Horizons in Pharmaceutical ScienceMark BraderMark BraderModerna, Inc., Cambridge, Massachusetts 02139, United StatesMore by Mark BraderView Biographyhttps://orcid.org/0000-0002-4735-408X, Hai-Young Anne KimHai-Young KimTherapeutic Discovery, Johnson and Johnson, Spring House, Pennsylvania 19477, KimView Biography, Otilia KooOtilia KooEmerging Technologies Portfolio Management, Novo Nordisk, Plainsboro, New Jersey 08536, KooView Karthik NagapudiKarthik NagapudiSynthetic Molecule Pharmaceutics, Genentech, South San Francisco, California 94080, NagapudiView Yongchao Su*Yongchao SuPharmaceutical Sciences Clinical Supply, Merck & Co., West Point, 19486, States*Email: [email protected]More SuView Biographyhttps://orcid.org/0000-0001-5063-3218Cite this: Mol. Pharmaceutics 2024, XXXX, XXX, XXX-XXXPublication Date (Web):May 28, 2024Publication History Received15 May 2024Published online28 2024https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.4c00544https://doi.org/10.1021/acs.molpharmaceut.4c00544editorialACS PublicationsPublished 2024 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions free to access through this site. Learn MoreArticle Views-Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum full text article downloads since November 2008 (both PDF HTML) across all institutions individuals. These metrics regularly updated reflect usage leading up last few days.Citations number other articles citing article, calculated Crossref daily. Find more information about citation counts.The Altmetric Attention Score a quantitative measure attention that research has received online. Clicking on donut icon will load page at altmetric.com with additional details score social media presence for given article. how calculated. Share Add toView InAdd Full Text ReferenceAdd Description ExportRISCitationCitation abstractCitation referencesMore Options onFacebookTwitterWechatLinked InRedditEmail (4 MB) Get e-AlertscloseSUBJECTS:Bioengineering biotechnology,Drug delivery,Industrial manufacturing,Pharmaceuticals,Quality management e-Alerts

Language: Английский

Citations

1
Molecular Investigation of SNAC as an Oral Peptide Permeation Enhancer in Lipid Membranes via Solid-State NMR DOI
Jing Ling,

Ryan Schroder,

W. Peter Wuelfing

et al.

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: 22(1), P. 459 - 473

Published: Dec. 17, 2024

Oral peptide therapeutics are increasingly favored in the pharmaceutical industry for their ease of use and better patient adherence. However, they face challenges with poor oral bioavailability due to high molecular weight surface polarity. Permeation enhancers (PEs) like salcaprozate sodium (SNAC) have shown promise clinical trials, achieving about 1% bioavailability. One proposed mechanism enhancing permeation is membrane perturbation or fluidization, though direct experimental proof quantitative analysis these effects still needed. This study employs solid-state NMR (ssNMR) investigate how SNAC interacts hydrated DMPC liposomes, measuring enhancements fluidity across interfacial transmembrane regions. The methodology involves analyzing phosphate lipid headgroups acyl chains using static

Language: Английский

Citations

0