Development of phage-loaded dissolving microneedles for microbiome modulation in acne

Abstract

Acne vulgaris is a chronic inflammatory skin disorder associated with dysbiosis of the cutaneous microbiome, characterised by reduced strain diversity and the predominance of acne-associated Cutibacterium acnes (C. acnes) phylotypes, particularly IA1 lineages. In contrast, healthy skin typically exhibits greater strain-level diversity within C. acnes populations. Conventional therapies frequently rely on broad-spectrum antibiotics, contributing to antimicrobial resistance and disruption of commensal microbial communities. There remains a clear need for targeted, microbiome-preserving therapeutic strategies capable of overcoming the skin barrier while addressing deep-seated bacterial biofilms.

This thesis describes the development and evaluation of dissolving microneedle (MN) arrays for the intradermal delivery of a strain-selective bacteriophage targeting acne-associated C. acnes. The work integrates phage characterisation, formulation optimisation, and biological evaluation across in vitro, ex vivo, and in vivo models. A selective phage was identified and characterised for host range, stability, and antibacterial activity. To enable incorporation within dissolving MN matrices, formulation strategies were developed to preserve phage viability during processing and storage. The delivery system demonstrated effective intradermal administration and significant antibacterial and antibiofilm activity within validated skin-relevant models. Safety and biocompatibility were assessed through sterility, cytotoxicity, and haemocompatibility studies, supporting the translational relevance of the platform.

Overall, this work establishes proof-of-concept for microbiome modulation via intradermal biologic delivery and highlights the potential of targeted bacteriophage therapy as an alternative approach to conventional broad-spectrum antibiotic treatments for inflammatory skin disease.

Thesis is embargoed until 31 July 2031.

Date of Award	Jul 2026
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	MRC IAA, Innovate UK & QUB Proof of Principle (PoP) Fund
Supervisor	Ryan Donnelly (Supervisor) & Tim Skvortsov (Supervisor)