AI Article Synopsis
- - The study examines the role of the neonatal Fc receptor (FcRn) in drug delivery through the nasal route, specifically for therapeutic antibodies used in neurological diseases. - Researchers found that FcRn is present in various cells within the olfactory mucosa and that it facilitates the uptake of allogenic (same species) IgGs, though less so for xenogenic (different species) human IgGs. - The findings suggest that FcRn-mediated transport could enhance intranasal drug delivery effectiveness, but concerns regarding immune responses in lymphoid follicles need further investigation to prevent potential immunogenic reactions.
Article Abstract
Background: The use of therapeutic antibodies for the treatment of neurological diseases is of increasing interest. Nose-to-brain drug delivery is one strategy to bypass the blood brain barrier. The neonatal Fc receptor (FcRn) plays an important role in transepithelial transcytosis of immunoglobulin G (IgG). Recently, the presence of the FcRn was observed in nasal respiratory mucosa. The aim of the present study was to determine the presence of functional FcRn in olfactory mucosa and to evaluate its role in drug delivery.
Methods: Immunoreactivity and messenger RNA (mRNA) expression of FcRn was determined in ex vivo porcine olfactory mucosa. Uptake of IgG was performed in a side-by-side cell and analysed by immunofluorescence.
Results: FcRn was found in epithelial and basal cells of the olfactory epithelium as well as in glands, cavernous bodies and blood vessels. Allogenic porcine IgGs were found time-dependently in the and along axonal bundles, while only small amounts of xenogenic human IgGs were detected. Interestingly, lymphoid follicles were spared from allogenic IgGs.
Conclusion: Fc-mediated transport of IgG across the nasal epithelial barrier may have significant potential for intranasal delivery, but the relevance of immune interaction in lymphoid follicles must be clarified to avoid immunogenicity.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161100 | PMC |
| http://dx.doi.org/10.3390/pharmaceutics10030107 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Preclinical evaluation of 64Cu/177Lu-labelled anti-CD30 monoclonal antibody for theranostics in CD30-positive lymphoma.
Eur J Nucl Med Mol Imaging
December 2024
Department of Nuclear Medicine, Beijing Friendship Hospital, Capital Medical University, 95 Yong An Road, Xi Cheng District, Beijing, 100050, China.
Purpose: CD30 serves as an ideal therapeutic target for lymphoma, but its variable expression and high relapse rate pose challenges in targeted therapy. This study aims to label the anti-CD30 monoclonal antibody with Cu/Lu for immuno-positron emission tomography (immuno-PET) and radioimmunotherapy (RIT).
Methods: CD30 binding kinetics of anti-CD30-IgG (IMB16) were measured by Biolayer interferometry (BLI).
New Cellular Models to Support Preclinical Studies on ICAM-1-Targeted Drug Delivery.
J Drug Deliv Sci Technol
November 2024
Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology (BIST), Barcelona, 08028, Spain.
Intercellular adhesion molecule 1 (ICAM-1) is a cell-surface protein actively explored for targeted drug delivery. Anti-ICAM-1 nanocarriers (NCs) target ICAM-1-positive sites after intravenous injection in animal models, but quantitative mechanistic examination of cellular-level transport in vivo is not possible. Prior studies in human cell cultures indicated efficient uptake of these formulations via cell adhesion molecule-(CAM)-mediated endocytosis.
View Article and Find Full Text PDFPreclinical Comparison of [In]In- and [Ac]Ac-DOTA-Trastuzumab IgG, F(ab') and Fab for Theranostic SPECT/CT Imaging and α-Particle Radioimmunotherapy of HER2-Positive Human Breast Cancer.
Mol Pharm
December 2024
Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON M5S 3M2, Canada.
Radioimmunotherapy (RIT) with α-particle-emitting, Ac complexed to trastuzumab may offer an alternative treatment for patients who progress on HER2-targeted therapies. Moreover, RIT with [Ac]Ac-DOTA-trastuzumab could be combined with SPECT/CT imaging with [In]In-DOTA-trastuzumab in a theranostic approach. In this study, we compared DOTA-conjugated trastuzumab IgG, F(ab') or Fab complexed to In or Ac for SPECT/CT imaging and α-particle RIT of subcutaneous (s.
View Article and Find Full Text PDFCell membrane-coated mRNA nanoparticles for enhanced delivery to dendritic cells and immunotherapy.
Asian J Pharm Sci
December 2024
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Cationic polymers such as polyethylenimine have been considered promising carriers for mRNA vaccines. However, their application is hindered by their inherent toxicity and a lack of targeted delivery capability. These issues need to be addressed to develop effective cancer vaccines.
View Article and Find Full Text PDFLiposome-loaded dissolvable microneedle patches for more efficient intradermal antigen delivery of Hepatitis B vaccine.
Int J Pharm
December 2024
Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Shanghai 201203, China. Electronic address:
The aim of this study was to improve the efficacy of Hepatitis B surface antigen (HBsAg) vaccination via liposome-loaded dissolvable microneedle (Lipo-dMN) patches. HBsAg liposomes were prepared using the thin-film hydration method and subsequently incorporated into dissolvable microneedle patches via a pre-vacuum approach. Liposomes, dissolvable microneedle patches (dMN), and Lipo-dMN were characterized for encapsulation efficiency, mechanical properties, morphology, skin insertion, in vitro release, cellular uptake, and in vivo vaccination studies.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!