Mucoadhesive pickering nanoemulsions via dynamic covalent chemistry

Saul J Hunter; Mahmoud H Abu Elella; Edwin C Johnson; Laura Taramova; Emma E Brotherton; Steven P Armes; Vitaliy V Khutoryanskiy; Mark J Smallridge

doi:10.1016/j.jcis.2023.07.162

Mucoadhesive pickering nanoemulsions via dynamic covalent chemistry

J Colloid Interface Sci. 2023 Dec:651:334-345. doi: 10.1016/j.jcis.2023.07.162. Epub 2023 Jul 27.

Authors

Saul J Hunter¹, Mahmoud H Abu Elella², Edwin C Johnson¹, Laura Taramova³, Emma E Brotherton¹, Steven P Armes⁴, Vitaliy V Khutoryanskiy⁵, Mark J Smallridge⁶

Affiliations

¹ Dainton Building, Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, South Yorkshire S3 7HF, UK.
² Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AD, UK; Chemistry Department, Faculty of Science, Cairo University, Giza 12613, Egypt.
³ Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AD, UK.
⁴ Dainton Building, Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, South Yorkshire S3 7HF, UK. Electronic address: s.p.armes@sheffield.ac.uk.
⁵ Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AD, UK. Electronic address: v.khutoryanskiy@reading.ac.uk.
⁶ GEO Specialty Chemicals, Hythe, Southampton, Hampshire SO45 3ZG, UK.

PMID: 37544222
DOI: 10.1016/j.jcis.2023.07.162

Abstract

Hypothesis: Submicron oil droplets stabilized using aldehyde-functionalized nanoparticles should adhere to the primary amine groups present at the surface of sheep nasal mucosal tissue via Schiff base chemistry.

Experiments: Well-defined sterically-stabilized diblock copolymer nanoparticles of 20 nm diameter were prepared in the form of concentrated aqueous dispersions via reversible addition-fragmentation chain transfer (RAFT) aqueous emulsion polymerization of 2,2,2-trifluoroethyl methacrylate (TFEMA) using a water-soluble methacrylic precursor bearing cis-diol groups. Some of these hydroxyl-functional nanoparticles were then selectively oxidized using an aqueous solution of sodium periodate to form a second batch of nanoparticles bearing pendent aldehyde groups within the steric stabilizer chains. Subjecting either hydroxyl- or aldehyde-functional nanoparticles to high-shear homogenization with a model oil (squalane) produced oil-in-water Pickering macroemulsions of 20-30 µm diameter. High-pressure microfluidization of such macroemulsions led to formation of the corresponding Pickering nanoemulsions with a mean droplet diameter of around 200 nm. Quartz crystal microbalance (QCM) experiments were used to examine adsorption of both nanoparticles and oil droplets onto a model planar substrate bearing primary amine groups, while a fluorescence microscopy-based mucoadhesion assay was developed to assess adsorption of the oil droplets onto sheep nasal mucosal tissue.

Findings: Squalane droplets coated with aldehyde-functional nanoparticles adhered significantly more strongly to sheep nasal mucosal tissue than those coated with the corresponding hydroxyl-functional nanoparticles. This difference was attributed to the formation of surface imine bonds via Schiff base chemistry and was also observed for the two types of nanoparticles alone in QCM studies. Preliminary biocompatibility studies using planaria indicated only mild toxicity for these new mucoadhesive Pickering nanoemulsions, suggesting potential applications for the localized delivery of hydrophobic drugs.

Keywords: Aldehyde-functional; Block copolymers; Mucoadhesion; Nanoemulsions; Pickering emulsions; Schiff base chemistry; Sterically-stabilized nanoparticles.