Photosensitizer-eluting nanofibers for enhanced photodynamic therapy of wounds: A preclinical study in immunocompromized rats

Abstract

Electrospun nanofibers (NFs) as drug delivery/tissue regeneration template and antimicrobial photodynamic therapy (APDT) have been widely investigated as two different approaches to enhance wound healing. In the present study, the two approaches were combined in a single platform for greater healing enhancement potentials. Composite photosensitizer-eluting NFs were developed using a polyhydrohybutyrate/polyethylene glycol (60:40 PHB/PEG) polymer blend and methylene blue (MB) as antimicrobial photosensitizer (PS). NFs protected the photoactivity of entrapped MB, enhanced its photodynamic activity against two wound bacteria, Staphylococcus aureus standard strain (SA_st) and MRSA and sustained MB release allowing for flexible PS dosing and irradiation schedules. This combined PS-eluting NFs/APDT approach proved effective in the treatment of SA_st-inoculated excision wounds in a challenging immunocompromized rat model. This was verified by morphological, morphometric, microbiological, histopathological and RT-PCR studies. Inclusion of PS-eluting NFs as an additional active component of APDT generates a combined non-antibiotic antimicrobial/cell regeneration approach with great potentials for wound healing and other biomedical applications.

Keywords: Chloroform (PubChem CID: 6212); Composite nanofibers; Immunocompromized rats; Methylene blue; Methylene blue (PubChem CID: 104827); Photodynamic therapy; Poly-ethylene glycol (PubChem CID: 174); Polyhydroxybutyrate; Polyhydroxybutyrate (PubChem CID: 13061653); Span 80 (sorbitan monooleate) (PubChem CID: 9920342); Wound healing.