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1.
Eur J Pharm Biopharm ; 152: 327-339, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32473289

ABSTRACT

Wound healing is a complex and costly public health problem that should be timely addressed to achieve a rapid and adequate tissue repair avoiding or even eliminating potential pathogenic infection. Chronic infected non-healing wounds represent a serious concern for health care systems. Efficient wound dressings with tailored therapy having the best response and highest safety margin for the management of chronic non-healing wounds are still needed. The use of novel wound dressing materials has emerged as a promising tool to fulfil these requirements. In this work, asymmetric electrospun polycaprolactone (PCL)-based nanofibers (NFs) were decorated with electrosprayed poly(lactic-co-glycolic acid) microparticles (PLGA MPs) containing the natural antibacterial compound thymol (THY) in order to obtain drug eluting antimicrobial dressings having sustained release. The synthesized dressings successfully inhibited the in vitro growth of Staphylococcus aureus ATCC 25923, showing also at the same doses cytocompatibility on human dermal fibroblasts and keratinocyte cultures after treatment for 24 h, which was not observed when using free thymol. An in vivo murine excisional wound splinting model, followed by the experimental infection of the wounds with S. aureus and their treatment with the synthesized dressings, pointed to the reduction of the bacterial load in wounds after 7 days, though the total elimination of the infection was not reached. The findings indicated the relevance of the direct contact between the dressings and the bacteria, highlighting the need to tune their design considering the wound surface and the nature of the antimicrobial cargo contained.


Subject(s)
Anti-Bacterial Agents/pharmacology , Delayed-Action Preparations/pharmacology , Thymol/pharmacology , Wound Healing/drug effects , Animals , Anti-Bacterial Agents/chemistry , Bandages , Cell Line , Delayed-Action Preparations/chemistry , Fibroblasts/drug effects , Fibroblasts/microbiology , Humans , Male , Mice , Nanofibers/chemistry , Polyesters/chemistry , Skin/drug effects , Skin/microbiology , Staphylococcal Infections/drug therapy , Staphylococcus aureus/drug effects , Thymol/chemistry
2.
Int J Pharm ; 577: 119067, 2020 Mar 15.
Article in English | MEDLINE | ID: mdl-31981705

ABSTRACT

Wound healing is a complex process that consists of three overlapping phases: inflammation, proliferation, and remodeling. A bacterial infection can increase inflammation and delay this process. Microorganisms are closely related to the innate immune system, such as macrophages and neutrophils, as they can start an inflammatory cascade. Essential oils play an important role in the inhibition and prevention of bacterial growth due to their ability to reduce antimicrobial resistance. The possibility to find a strategy that combines antimicrobial and anti-inflammatory properties is particularly appealing for wound healing. In this work, we showcase a variety of patches based on electrospun polycaprolactone (PCL) nanofibers loaded with natural compounds derived from essential oils, such as thymol (THY) and tyrosol (TYR), to achieve reduced inflammation. In addition, we compared the effect these essential oils have on activated macrophages when incorporated into the PCL patch. Specifically, we demonstrate that PCL-THY resulted in more efficient down-regulation of pro-inflammatory genes related to the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κb) pathway when compared to PCL-TYR and the combination patch containing TYR and THY (i.e., PCL-TYR-THY). Furthermore, PCL-THY displayed low affinity for cell attachment, which may hinder wound adherence and integration. Overall, our results indicate that THY-loaded patches could serve as promising candidates for the fabrication of dressings that incorporate bactericidal and anti-inflammatory properties while simultaneously avoiding the limitations of traditional antibiotic-loaded devices.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Nanofibers , Oils, Volatile/pharmacology , Wound Healing/drug effects , Animals , Anti-Inflammatory Agents/administration & dosage , Cell Line , Inflammation/drug therapy , Inflammation/pathology , Macrophages/drug effects , Macrophages/pathology , Mice , Oils, Volatile/administration & dosage , Polyesters/chemistry
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