Biodegradable pH-Sensitive Poly(ethylene glycol) Nanocarriers for Allergen Encapsulation and Controlled Release.
In the last decades, the number of allergic patients has increased dramatically. Allergen-specific immunotherapy (SIT) is the only available cause-oriented therapy so far. SIT reduces the allergic symptoms, but also exhibits some disadvantages; that is, it is a long-lasting procedure and severe side effects like anaphylactic shock can occur. In this work, we introduce a method to encapsulate allergens into nanoparticles to avoid severe side effects during SIT. Degradable nanocarriers combine the advantage of providing a physical barrier between the encapsulated cargo and the biological environment as well as responding to certain local stimuli (like pH) to release their cargo. This work introduces a facile strategy for the synthesis of acid-labile poly(ethylene glycol) (PEG)-macromonomers that degrade at pH 5 (physiological pH inside the endolysosome) and can be used for nanocarrier synthesis. The difunctional, water-soluble PEG dimethacrylate (PEG-acetal-DMA) macromonomers with cleavable acetal units were analyzed with 1H NMR, SEC, and MALDI-ToF-MS. Both the allergen and the macromonomers were entrapped inside liposomes as templates, which were produced by dual centrifugation (DAC). Radical polymerization of the methacrylate units inside the liposomes generated allergen-loaded PEG nanocarriers. In vitro studies demonstrated that dendritic cells (DCs) internalize the protein-loaded, nontoxic PEG-nanocarriers. Furthermore, we demonstrate by cellular antigen stimulation tests that the nanocarriers effectively shield the allergen cargo from detection by immunoglobulins on the surface of basophilic leucocytes. Uptake of nanocarriers into DCs does not lead to cell maturation; however, the internalized allergen was capable to induce T cell immune responses.
Department of Dermatology, University Medical Center Mainz , Langenbeckstr. 1, 55131 Mainz, Germany.|Institute of Organic Chemistry, University of Mainz , Duesbergweg 10-14, 55128 Mainz, Germany.|Graduate School Materials Science in Mainz, Staudinger Weg 9, 55128 Mainz, Germany.
Hannah
H
Pohlit
Department of Dermatology, University Medical Center Mainz , Langenbeckstr. 1, 55131 Mainz, Germany.
Iris
I
Bellinghausen
Institute of Organic Chemistry, University of Mainz , Duesbergweg 10-14, 55128 Mainz, Germany.
Martina
M
Schömer
Department of Dermatology, University Medical Center Mainz , Langenbeckstr. 1, 55131 Mainz, Germany.
Bärbel
B
Heydenreich
Department of Dermatology, University Medical Center Mainz , Langenbeckstr. 1, 55131 Mainz, Germany.
Joachim
J
Saloga
Institute of Organic Chemistry, University of Mainz , Duesbergweg 10-14, 55128 Mainz, Germany.
Holger
H
Frey
D000485:Allergens / Q000008:administration & dosage* / Q000737:chemistry; D002850:Chromatography, Gel; D004337:Drug Carriers; D006801:Humans; D006863:Hydrogen-Ion Concentration; D036103:Nanotechnology; D011092:Polyethylene Glycols / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000485:Allergens; D004337:Drug Carriers; D011092:Polyethylene Glycols