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The delivery of biopharmaceuticals to the oral mucosa offers a range of potential applications including antimicrobial peptides to treat resistant infections, growth factors for tissue regeneration, or as an alternative to injections for systemic delivery. Existing formulations targeting this site are typically non-specific and provide little control over dose. To address this, an electrospun dual-layer mucoadhesive patch was investigated for protein delivery to the oral mucosa. Lysozyme was used as a model antimicrobial protein and incorporated into poly(vinylpyrrolidone)/Eudragit RS100 polymer nanofibers using electrospinning from an ethanol/water mixture. The resulting fibrous membranes released the protein at a clinically desirable rate, reaching 90 ± 13% cumulative release after 2 h. Dual fluorescent fibre labelling and confocal microscopy demonstrated the homogeneity of lysozyme and polymer distribution. High encapsulation efficiency and preservation of enzyme activity were achieved (93.4 ± 7.0% and 96.1 ± 3.3% respectively). The released lysozyme inhibited the growth of the oral bacterium Streptococcus ratti, providing further evidence of retention of biological activity and illustrating a potential application for treating and preventing oral infections. An additional protective poly(caprolactone) backing layer was introduced to promote unidirectional delivery, without loss of enzyme activity, and the resulting dual-layer patches displayed long residence times using an in vitro test, showing that the adhesive properties were maintained. This study demonstrates that the drug delivery system has great potential for the delivery of therapeutic proteins to the oral mucosa., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The research presented was funding in part by AFYX Therapeutics. Dr H, Mr J Edmans, Dr S Spain and Professor C Murdoch declare that they have no other known competing financial interests or personal relationships that could have appeared to influence the work reported within this paper. Dr M E. Santocildes-Romero is employed by AFYX Therapeutics. Professor P V. Hatton is on the AFYX Therapeutics APS Scientific Advisory Board, where AFYX have translated mucoadhesive electrospun patch technology for clinical use and have intellectual property (international patent application WO 2017/085262 A)., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Intercalation of drugs into assembled DNA systems offers versatile new mechanisms for controlled drug delivery. However, current systems are becoming increasingly complex, reducing the practicality of large scale production. Here, we demonstrate a more pragmatic approach where a short DNA sequence was modified with poly(ethylene glycol) (PEG) of various lengths at both 5'-termini to provide serum stability and compatibility. The anticancer drug doxorubicin was physically loaded into two designed binding sites on the dsODN. The polymer conjugation improved the stability of the dsODN toward serum nucleases while its doxorubicin binding affinity was unaffected by the presence of the polymers. We examined the effects of polymer size on the dsODN carrier characteristics and studied the resulting DOX@DNA-PEG systems with respect to cytotoxicity, cellular uptake, and localization in A549 and MCF7 cell lines. For the A549 cell line the DOX@DNA-PEG1900 exhibited the best dose response of the conjugates while DOX@DNA-PEG550 was the least potent. In MCF-7, a more doxorubicin sensitive cell line, all conjugates exhibited similar dose response to that of the free drug. Confocal microscopy analysis of doxorubicin localization shows that conjugates successfully deliver doxorubicin to the cell nucleus and also the lysosome. These data provide a valuable insight into the complexities of designing an oligonucleotide based drug delivery system and highlight some practical issues that need to be considered when doing so.