Wound healing is a complex and multistage process that incorporates precise cellular and molecular coordination. The presence of biofilms in chronic wounds adversely affects the wound healing process, as it prolongs the closure of the wound, thus sustaining chronic inflammation. Current data suggest that biofilms are present in almost all chronic wounds, which leads to significant challenges in diagnosis and treatment. Traditional detection methods, such as cultures and light microscopy, often fail to detect biofilms; however, sophisticated molecular and imaging techniques are constrained by their expense and accessibility. Chronic wound management, therefore, has progressed from conventional antimicrobial application to integrated methodologies that incorporate biofilm debridement, antibiofilm dressing, negative pressure wound therapy, and innovative enzyme or nanoparticle interventions. This review highlights the clinical significance of biofilm presence as a barrier in chronic wound healing, assesses diagnostic and therapeutic innovations, and stresses the urgent need to improve patient outcomes.

Phytochemicals are effective and are gaining attention in fighting against drug-resistant bacterial strains. In the present study, rutin and quercetin were tested for antibacterial, antibiofilm, and wound healing activities on excision wounds infected with MDR-P. aeruginosa in diabetic mice. Antibacterial and antibiofilm activities were studied in vitro using broth dilution assay and crystal violet assay, respectively. These phytochemicals were tested alone for wound-healing activities at different concentrations (0.5% and 1% in ointment base) and in combination with gentamicin to evaluate any additive effects. Rutin and quercetin demonstrated effectiveness against MDR-P. aeruginosa at higher concentrations. Both phytochemicals inhibited biofilm formation in vitro and contributed to the healing of diabetic wounds by eradicating biofilm in the wounded tissue. Rutin at a low concentration (0.5%) had a lesser effect on reducing the epithelization period and regeneration of the epithelial layer compared to quercetin. When combined with gentamicin, quercetin (1%) displayed the maximum effect on epithelium regeneration, followed by rutin (1%) in combination with gentamicin. Both phytochemicals were found to be more effective in controlling biofilm and wound-healing activities when used as an additive with gentamicin. The study supports the traditional use of phytochemicals with antibacterial, antibiofilm, and wound-healing activities in managing diabetic infections.

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of infection worldwide. Clove oil’s ability to inhibit the growth of MRSA was studied through in vitro and in vivo studies. The phytochemical components of clove oil were determined through gas chromatography-mass spectrometry (GC-MS) analysis. The antibacterial effects of clove oil and its interaction with imipenem were determined by studying MIC, MBC, and FIC indices in vitro. The in vivo wound-healing effect of the clove oil and infection control were determined using excision wound model rats. The GC-MS analysis of clove oil revealed the presence of 16 volatile compounds. Clove oil showed a good antibacterial effect in vitro but no interaction was observed with imipenem. Clove bud oil alone or in combination with imipenem healed wounds faster and reduced the microbial load in wounds. The findings of this study confirmed the antibacterial activity of clove oil in vitro and in vivo and demonstrated its interaction with imipenem.

Antimicrobial resistance (AMR) is a present, pressing global public health crisis associated with rising morbidity and mortality rates due to previously curable infectious disease. Targeted drug delivery is an important approach to address AMR due to its ability to improve the therapeutic performance of antibiotics without leading to any adverse effects or organ toxicities. In this review we explore molecular mechanisms of AMR and drawbacks of conventional antibiotic therapies and discuss unique drug delivery approaches to compensate these. Nanoparticulate carrier systems, stimuli-responsive systems, antibody–drug conjugates, and CRISPR-Cas systems are some of the carrier method designs that are promising for tackling hard to treat infections related to pathogenic strains and biofilms due to their features. Many of these are among the most significant advances in the field. However, there are many challenges to be overcome, with biological limitations, scaling and regulatory challenges, etc., before they can be employed in commercial applications. Materials are being developed, and an approach standardized and applicable to future work is in development to improve the efficiency of targeted delivery systems. Controlled drug delivery, which could be the answer to an increasing AMR problem, will not only help in alerting awareness among individuals but will also help in prolonging the activity of antibiotics by providing synergistic interdisciplinary solutions. This review emphasizes the complementary role of targeted drug delivery in transitioning from laboratory investigations to clinical therapy. It addresses underrepresented aspects, including new materials, scalability, regulatory considerations, and ethical implications, while offering a roadmap for translating innovations into next-generation antimicrobials.

Frankincense (Boswellia sacra oleo gum resin) is reported to possess antimicrobial activity against several pathogens in-vitro. The antimicrobial effects of frankincense oil and its interaction with imipenem and gentamicin against methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant P. aeruginosa were determined through in-vitro methods and an in-vivo study using a rat pneumonia model. Frankincense oil was subjected to GC-MS analysis to determine the different volatile components. Antibacterial effects against MRSA and MDR-P. aeruginosa was evaluated and its MIC and MBC were determined. For the rat pneumonia model (in-vivo), oil was administered at a dose of 500 mg/kg and 1000 mg/kg followed by determination of CFU in lung tissue and histological studies. Frankincense oil did not show a very potent inhibitory effect against MRSA or MDR-P. aeruginosa; the oil did not affect the zone of inhibition or FIC when combined with imipenem or gentamicin indicating a lack of interaction between the oil and the antibiotics. Furthermore, there was no interaction between the antibiotics and the frankincense oil in the in-vivo model. The result of the study revealed that frankincense oil has a weak inhibitory effect against MRSA and MDR-P. aeruginosa, and it did not show any interaction with imipenem or gentamicin.

Achillea fragrantissima, a desert plant commonly known as yarrow, is traditionally used as an antimicrobial agent in folklore medicine in Saudi Arabia. The current study was undertaken to determine its antibiofilm activity against methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug-resistant Pseudomonas aeruginosa (MDR-P. aeruginosa) using in vitro and in vivo studies. A biofilm model induced through an excision wound in diabetic mice was used to evaluate its effect in vivo. The skin irritation and cytotoxic effects of the extract were determined using mice and HaCaT cell lines, respectively. The Achillea fragrantissima methanolic extract was analyzed with LC-MS to detect different phytoconstituents, which revealed the presence of 47 different phytoconstituents. The extract inhibited the growth of both tested pathogens in vitro. It also increased the healing of biofilm-formed excision wounds, demonstrating its antibiofilm, antimicrobial, and wound-healing action in vivo. The effect of the extract was concentration-dependent, and its activity was stronger against MRSA than MDR-P. aeruginosa. The extract formulation was devoid of a skin irritation effect in vivo and cytotoxic effect on HaCaT cell lines in vitro.