Abstract
Mucus lines the moist cavities throughout the body, acting as barrier by protecting the underlying cells against the external environment, but it also hinders the permeation of drugs and drug delivery systems. As the rate of diffusion is low, the development of a system which could increase retention time at the mucosal surface would prove beneficial. Here, we have designed a range of branched copolymers to act as functional mucus-responsive oil-in-water emulsifiers comprising the hydrophilic monomer oligo(ethylene glycol) methacrylate and a hydrophobic dodecyl initiator. The study aimed to investigate the importance of chain end functionality on successful emulsion formation, by systematically replacing a fraction of the hydrophobic chain ends with a secondary poly(ethylene glycol) based hydrophilic initiator in a mixed-initiation strategy; a decrease of up to 75 mole percent of hydrophobic chain ends within the branched polymer emulsifiers was shown to maintain comparative emulsion stability. These redundant chain ends allowed for functionality to be incorporated into the polymers via a xanthate based initiator containing a masked thiol group; thiol groups are known to have mucoadhesive character, due to their ability to form disulfide bonds with the cysteine rich areas of mucus. The mucoadhesive nature of emulsions stabilised by thiol-containing branched copolymers was compared to non-functional emulsions in the presence of a biosimilar mucosal substrate and enhanced adherence to the mucosal surface was observed. Importantly, droplet rupture and mucus triggered release of dye-containing oil was seen from previously highly-stable thiol-functional emulsions; this observation was not mirrored by non-functional emulsions where droplet integrity was maintained even in the presence of mucus.
Highlights
Mucous membranes create the moist exterior of various regions of the body including oral, gastrointestinal (GI), genital and ocular surfaces
We have recently reported the formation and application of branched copolymers consisting of OEGMA (Mn 1⁄4 300 g molÀ1) and ethylene glycol dimethacrylate (EGDMA), initiated by dodecyl a-bromoisobutyrate, 1 (Dod-Br, Scheme 1), under atom transfer radical polymerisation (ATRP) conditions, as highly efficient polymeric surfactants; the copolymers contain a hydrophobic dodecyl group at every chain-end.[24]
We hypothesised that initiating this copolymerisation with mixed initiator feedstocks would allow the creation of branched copolymers with varying chain-end composition; the decrease in hydrophobic chain-ends may potentially impair the surfactant behaviour of the branched copolymers
Summary
Mucous membranes create the moist exterior of various regions of the body including oral, gastrointestinal (GI), genital and ocular surfaces. Mucosa varies across different anatomical sites with different life-cycles and thicknesses that depend primarily on its speci c local function.[3,4,5] As a biologically-derived hydrogel[6] with de ned viscoelasticity, rheology and mesh size, mucous membranes act to moderate the passage of exogenous. Disul de bridges between cysteine residues contribute to the physical properties of the mucosal membrane; these sulfur-containing domains offer a chemical target for mucoadhesion and mucopermeation strategies. Mucoadhesion is generally regarded as progressing through a two-step process,[8] namely contact and consolidation. The material in contact with the mucus may be removed through various shear or stress modes and consolidation of the interaction is required to generate a long-acting
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