RESUMO
Sepsis following burn trauma is a global complication with high mortality, with ~60% of burn patient deaths resulting from infectious complications. Sepsis diagnosis is complicated by confounding clinical manifestations of the burn injury, and current biomarkers markers lack the sensitivity and specificity required for prompt treatment. Circulating extracellular vesicles (EVs) from patient liquid biopsy as biomarkers of sepsis due to their release by pathogens from bacterial biofilms and roles in subsequent immune response. This study applies Raman spectroscopy to patient plasma derived EVs for rapid, sensitive, and specific detection of sepsis in burn patients, achieving 97.5% sensitivity and 90.0% specificity. Furthermore, spectral differences between septic and non-septic burn patient EVs could be traced to specific glycoconjugates of bacterial strains associated with sepsis morbidity. This work illustrates the potential application of EVs as biomarkers in clinical burn trauma care, and establishes Raman analysis as a fast, label-free method to specifically identify features of bacterial EVs relevant to infection amongst the host background.
RESUMO
HIV and hepatitis B are two of the most prevalent viruses globally, and despite readily available preventive treatments unforgiving treatment regimens still exist, such as daily doses of medicine that are challenging to maintain especially in poorer countries. More advanced and longer-lasting delivery vehicles can potentially overcome this problem by reducing maintenance requirements and significantly increase access to medicine. Here, we designed a technology to control the delivery of an antiviral drug over a long timeframe via a nanofiber based delivery scaffold that is both easy to produce and use. An antiviral prodrug containing tenofovir alafenamide (TAF) was synthesized by initial conjugation to glycerol monomethacrylate followed by polymerization to form a diblock copolymer (pTAF) using reversible addition-fragmentation chain transfer (RAFT). In order to generate an efficient drug delivery system this copolymer was fabricated into an electrospun nanofiber (ESF) scaffold using blend electrospinning with poly(caprolactone) (PCL) as the carrier polymer. SEM images revealed that the pTAF-PCL ESFs were uniform with an average diameter of (787 ± 0.212 nm), while XPS analysis demonstrated that the pTAF was overrepresented at the surface of the ESFs. Additionally, the pTAF exhibited a sustained release profile over a 2 month period in human serum (HS), suggesting that these types of copolymer-based drugamers can be used in conjunction with electrospinning to produce long-lasting drug delivery systems.
