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Published on: March 9, 2019
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Targeted PEG-poly(glutamic acid) complexes for inhalation protein delivery to the lung
A Nieto-Orellana1, H Li1, R Rosiere2
1Molecular Therapeutics and Formulation Division, School of Pharmacy, University of Nottingham, Nottingham, UK.
Summary
Novel vitamin B12-targeted polymer nanoparticles enhance protein delivery to the lungs via inhalation. These targeted complexes show improved cellular uptake and lung retention with no significant toxicity, offering a promising pulmonary drug delivery system.
Area of Science:
- Biomaterials Science
- Pulmonary Drug Delivery
- Nanotechnology
Background:
- Pulmonary delivery offers a non-invasive route for protein therapeutics.
- Developing effective delivery systems for protein therapeutics is crucial for their clinical application.
- Vitamin B12 (cobalamin) receptor-mediated targeting presents a novel strategy for enhanced cellular uptake.
Purpose of the Study:
- To develop and evaluate vitamin B12-targeted poly(ethylene glycol)-block-poly(glutamic acid) (PEG-PGA) copolymers as complexing excipients for pulmonary protein delivery.
- To assess the cellular targeting, internalization, and in vivo performance of these novel complexes for inhalation.
- To investigate the safety and lung retention of the B12-targeted protein-loaded dry powder formulation.
Main Methods:
- Complexation of a model protein with B12-targeted PEG-PGA copolymers to form sub-200nm nanoparticles.
- Confirmation of vitamin B12 receptor (CD320) expression on Calu-3 lung epithelial cells.
- In vitro assessment of B12 receptor-mediated cellular internalization and spray drying for inhalation formulation.
- In vivo lung tolerance studies in mice and assessment of protein payload retention.
Main Results:
- B12-targeted complexes demonstrated enhanced cellular internalization via B12 receptor-mediated endocytosis in Calu-3 cells.
- Spray-dried powders exhibited suitable aerodynamic properties for lower airway deposition, with targeted complexes showing 2-3 fold higher cellular uptake from dry powder.
- In vivo studies revealed no significant toxicity or lung inflammation after repeated administration, and suggested enhanced lung retention of the protein payload with B12-targeted complexes.
Conclusions:
- Novel B12-targeted PEG-PGA copolymers are effective complexing excipients for protein pulmonary delivery.
- The developed dry powder formulation is suitable for inhalation, demonstrating enhanced cellular targeting and payload retention in the lungs.
- This approach shows potential for developing safe and effective inhaled protein therapeutics with improved efficacy.
Keywords:
Inhalation deliveryPolymer-protein complexesProtein deliverySpray-dried inhalation powderTargeted complexesMore Related Videos
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