Recent Patents on Light-Based Anti-Infective Approaches
Recent patents on anti-infective drug discovery, Nov 7, 2017
Antibiotic resistance is one of the most serious health threats to modern medicine. The lack of p... more Antibiotic resistance is one of the most serious health threats to modern medicine. The lack of potent antibiotics puts us at a disadvantage in the fight against infectious diseases, especially those caused by antibiotic-resistant microbial strains. To this end, an urgent need to search for alternative antimicrobial approaches has arisen. In the last decade, light-based therapy has made significant strides in this fight to combat antibiotic resistance among various microbial strains. This method includes utilizing antimicrobial blue light, antimicrobial photodynamic therapy, and germicidal ultraviolet irradiation, among others. Light-based therapy is advantageous over traditional antibiotic-based therapy in that it selectively eradicates microbial cells without harming human cells and tissues. This review highlights the patents on light-based therapy that were filed approximately within the last decade and are dedicated to eradicating pathogenic microbes. The treatments and devices ...
High incident fluence and long pulse laser irradiation in conjunction with cryogen spray cooling: an ex-vivo study
Proceedings of the Second Joint 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society] [Engineering in Medicine and Biology, 2000
Pseudomonas aeruginosa is among the most common pathogens that cause nosocomial infections and is... more Pseudomonas aeruginosa is among the most common pathogens that cause nosocomial infections and is responsible for about 10% of all hospital-acquired infections. In the present study, we investigated the potential development of tolerance of P. aeruginosa to antimicrobial blue light by carrying 10 successive cycles of sublethal blue light inactivation. The high-performance liquid chromatographic (HPLC) analysis was performed to identify endogenous porphyrins in P. aeruginosa cells. In addition, we tested the effectiveness of antimicrobial blue light in a mouse model of nonlethal skin abrasion infection by using a bioluminescent strain of P. aeruginosa. The results demonstrated that no tolerance was developed to antimicrobial blue light in P. aeruginosa after 10 cycles of sub-lethal inactivation. HPLC analysis showed that P. aeruginosa is capable of producing endogenous porphyrins in particularly, coproporphyrin III, which are assumed to be responsible for the photodynamic effects of ...
Biofilms affect more than 80% bacterial infections in human and are usually difficult to eradica... more Biofilms affect more than 80% bacterial infections in human and are usually difficult to eradicate due to their inherent drug resistance. We investigated the effectiveness of antimicrobial blue light (aBL; 415 nm) inactivation of Acinetobacter baumannii or Pseudomonas aeruginosa biofilms in 96-well microplates and in infected mouse burns. In vitro in 96-well microplates, 24-h and 72-h old biofilms of A. baumannii exposed to 432 J/cm(2) aBL had 3.59- and 3.18-log10 inactivation, respectively. For P. aeruginosa biofilms, a similar 3.02- and 3.12-log10 inactivation was achieved. In mouse burns infected with 5×10(6) CFU of A. baumannii, approximately 360 and 540 J/cm(2) aBL was required to achieve 3-log10 inactivation of biofilms when aBL was delivered at 24 and 48 h post-inoculation, respectively. High-performance liquid chromatography (HPLC) analysis revealed the presence of endogenous porphyrins in both A. baumannii and P. aeruginosa cells. Using the TUNEL assay, no apoptotic cell...
Fungal infections are a common cause of morbidity, mortality and cost in critical care population... more Fungal infections are a common cause of morbidity, mortality and cost in critical care populations. The increasing emergence of antimicrobial resistance necessitates the development of new therapeutic approaches for fungal infections. In the present study, we investigated the effectiveness of an innovative approach, antimicrobial blue light (aBL), for inactivation of Candida albicans in vitro and in infected mouse burns. A bioluminescent strain of C. albicans was used. The susceptibilities to aBL (415 nm) were compared between C. albicans and human keratinocytes. The potential development of aBL resistance by C. albicans was investigated via 10 serial passages of C. albicans on aBL exposure. For the animal study, a mouse model of thermal burn infected with the bioluminescent C. albicans strain was used. aBL was delivered to mouse burns approximately 12 h after fungal inoculation. Bioluminescence imaging was used to monitor in real time the extent of infection in mice. The results ob...
<title>Thermal response of human skin epidermis in different skin types to 595-nm laser irradiation and cryogen spray cooling: an ex-vivo study</title>
Lasers in Surgery: Advanced Characterization, Therapeutics, and Systems XIII, 2003
Wound-Healing Properties of Chitosan and Its Use in Wound Dressing Biopharmaceuticals
Delivery, Targeting and Polymer Therapeutics, 2012
ABSTRACT This chapter contains sections titled: IntroductionBrief Review of Wound RepairWound-Hea... more ABSTRACT This chapter contains sections titled: IntroductionBrief Review of Wound RepairWound-Healing Effects of ChitosanChitosan for Wound Therapeutics DeliveryConclusions and Future PerspectivesAcknowledgmentsReferences
Antimicrobial photodynamic inactivation with fullerenes bearing cationic charges may overcome res... more Antimicrobial photodynamic inactivation with fullerenes bearing cationic charges may overcome resistant microbes. We synthesized C60-fullerene (LC16) bearing decaquaternary chain and deca-tertiary-amino groups that facilitates electron-transfer reactions via the photoexcited fullerene. Addition of the harmless salt, potassium iodide (10 mM) potentiated the ultraviolet A (UVA) or white light-mediated killing of Gram-negative bacteria Acinetobacter baumannii, Gram-positive methicillin-resistant Staphylococcus aureus and fungal yeast Candida albicans by 1-2+ logs. Mouse model infected with bioluminescent Acinetobacter baumannii gave increased loss of bioluminescence when iodide (10 mM) was combined with LC16 and UVA/white light. The mechanism may involve photoinduced electron reduction of (1)(C60>)* or (3)(C60>)* by iodide producing I· or I2 followed by subsequent intermolecular electron-transfer events of (C60>)(-)· to produce reactive radicals.
BACKGROUND: Since the beginning of the conflicts in the Middle East, US Army physicians have note... more BACKGROUND: Since the beginning of the conflicts in the Middle East, US Army physicians have noted a high rate of multidrug-resistant Acinetobacter baumannii infections among US soldiers wounded and initially treated in Iraq. In this study, we investigated the use of ultraviolet C (UVC) light for prevention of multidrug-resistant A. baumannii wound infections using mouse models.
Background: Local microbial infections induced by multiple-drug-resistant bacteria in the orthope... more Background: Local microbial infections induced by multiple-drug-resistant bacteria in the orthopedic field can be intractable, therefore development of new therapeutic modalities is needed. Photodynamic therapy (PDT) is a promising alternative modality to antibiotics for intractable microbial infections, and we recently reported that PDT has the potential to accumulate neutrophils into the infected site which leads to resolution of the infection. PDT for cancer has long been known to be able to stimulate the innate and adaptive arms of the immune system.
Linezolid and vancomycin decrease the therapeutic effect of methylene blue-photodynamic therapy in a mouse model of MRSA bacterial arthritis
Photochemistry and Photobiology, 2013
We previously reported that photodynamic therapy (PDT) using intra-articular methylene blue (MB) ... more We previously reported that photodynamic therapy (PDT) using intra-articular methylene blue (MB) could be used to treat arthritis in mice caused by bioluminescent methicillin-resistant Staphylococcus aureus (MRSA) either in a therapeutic or in a preventative mode. PDT accumulated neutrophils into the mouse knee via activation of chemoattractants such as inflammatory cytokines or chemokines. In this study, we asked whether PDT combined with antibiotics used for MRSA could provide added benefit in controlling the infection. We compared MB-PDT alone, systemic administration of either linezolid (LZD) alone or vancomycin (VCM) alone or the combination of PDT with either LZD or VCM. Real-time noninvasive imaging was used to serially follow the progress of the infection. PDT alone was the most effective, whereas LZD alone was ineffective and VCM alone showed some benefit. Surprisingly the addition of LZD or VCM reduced the therapeutic effect of PDT alone (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Considering that PDT in this mouse model stimulates neutrophils to be antibacterial rather than actively killing the bacteria, we propose that LZD and VCM might inhibit the activation of inflammatory cytokines without eradicating the bacteria, and thereby reduce the therapeutic effect of PDT.
This article is a highlight of the study by Maclean et al. in this issue of Photochemistry and Ph... more This article is a highlight of the study by Maclean et al. in this issue of Photochemistry and Photobiology describing the sporicidal effects 405 nm visible light alone on endospores of the Clostridium and Bacillus genera. 1.73 kJ cm À2 was capable of reducing endospore colony-forming units by up to 4-log 10 . These findings have never been previously demonstrated and may be incorporated into decontamination methods that span medical, military and food preparatory applications.
Recent Patents on Light-Based Anti-Infective Approaches
Recent patents on anti-infective drug discovery, Nov 7, 2017
Antibiotic resistance is one of the most serious health threats to modern medicine. The lack of p... more Antibiotic resistance is one of the most serious health threats to modern medicine. The lack of potent antibiotics puts us at a disadvantage in the fight against infectious diseases, especially those caused by antibiotic-resistant microbial strains. To this end, an urgent need to search for alternative antimicrobial approaches has arisen. In the last decade, light-based therapy has made significant strides in this fight to combat antibiotic resistance among various microbial strains. This method includes utilizing antimicrobial blue light, antimicrobial photodynamic therapy, and germicidal ultraviolet irradiation, among others. Light-based therapy is advantageous over traditional antibiotic-based therapy in that it selectively eradicates microbial cells without harming human cells and tissues. This review highlights the patents on light-based therapy that were filed approximately within the last decade and are dedicated to eradicating pathogenic microbes. The treatments and devices ...
High incident fluence and long pulse laser irradiation in conjunction with cryogen spray cooling: an ex-vivo study
Proceedings of the Second Joint 24th Annual Conference and the Annual Fall Meeting of the Biomedical Engineering Society] [Engineering in Medicine and Biology, 2000
Pseudomonas aeruginosa is among the most common pathogens that cause nosocomial infections and is... more Pseudomonas aeruginosa is among the most common pathogens that cause nosocomial infections and is responsible for about 10% of all hospital-acquired infections. In the present study, we investigated the potential development of tolerance of P. aeruginosa to antimicrobial blue light by carrying 10 successive cycles of sublethal blue light inactivation. The high-performance liquid chromatographic (HPLC) analysis was performed to identify endogenous porphyrins in P. aeruginosa cells. In addition, we tested the effectiveness of antimicrobial blue light in a mouse model of nonlethal skin abrasion infection by using a bioluminescent strain of P. aeruginosa. The results demonstrated that no tolerance was developed to antimicrobial blue light in P. aeruginosa after 10 cycles of sub-lethal inactivation. HPLC analysis showed that P. aeruginosa is capable of producing endogenous porphyrins in particularly, coproporphyrin III, which are assumed to be responsible for the photodynamic effects of ...
Biofilms affect more than 80% bacterial infections in human and are usually difficult to eradica... more Biofilms affect more than 80% bacterial infections in human and are usually difficult to eradicate due to their inherent drug resistance. We investigated the effectiveness of antimicrobial blue light (aBL; 415 nm) inactivation of Acinetobacter baumannii or Pseudomonas aeruginosa biofilms in 96-well microplates and in infected mouse burns. In vitro in 96-well microplates, 24-h and 72-h old biofilms of A. baumannii exposed to 432 J/cm(2) aBL had 3.59- and 3.18-log10 inactivation, respectively. For P. aeruginosa biofilms, a similar 3.02- and 3.12-log10 inactivation was achieved. In mouse burns infected with 5×10(6) CFU of A. baumannii, approximately 360 and 540 J/cm(2) aBL was required to achieve 3-log10 inactivation of biofilms when aBL was delivered at 24 and 48 h post-inoculation, respectively. High-performance liquid chromatography (HPLC) analysis revealed the presence of endogenous porphyrins in both A. baumannii and P. aeruginosa cells. Using the TUNEL assay, no apoptotic cell...
Fungal infections are a common cause of morbidity, mortality and cost in critical care population... more Fungal infections are a common cause of morbidity, mortality and cost in critical care populations. The increasing emergence of antimicrobial resistance necessitates the development of new therapeutic approaches for fungal infections. In the present study, we investigated the effectiveness of an innovative approach, antimicrobial blue light (aBL), for inactivation of Candida albicans in vitro and in infected mouse burns. A bioluminescent strain of C. albicans was used. The susceptibilities to aBL (415 nm) were compared between C. albicans and human keratinocytes. The potential development of aBL resistance by C. albicans was investigated via 10 serial passages of C. albicans on aBL exposure. For the animal study, a mouse model of thermal burn infected with the bioluminescent C. albicans strain was used. aBL was delivered to mouse burns approximately 12 h after fungal inoculation. Bioluminescence imaging was used to monitor in real time the extent of infection in mice. The results ob...
<title>Thermal response of human skin epidermis in different skin types to 595-nm laser irradiation and cryogen spray cooling: an ex-vivo study</title>
Lasers in Surgery: Advanced Characterization, Therapeutics, and Systems XIII, 2003
Wound-Healing Properties of Chitosan and Its Use in Wound Dressing Biopharmaceuticals
Delivery, Targeting and Polymer Therapeutics, 2012
ABSTRACT This chapter contains sections titled: IntroductionBrief Review of Wound RepairWound-Hea... more ABSTRACT This chapter contains sections titled: IntroductionBrief Review of Wound RepairWound-Healing Effects of ChitosanChitosan for Wound Therapeutics DeliveryConclusions and Future PerspectivesAcknowledgmentsReferences
Antimicrobial photodynamic inactivation with fullerenes bearing cationic charges may overcome res... more Antimicrobial photodynamic inactivation with fullerenes bearing cationic charges may overcome resistant microbes. We synthesized C60-fullerene (LC16) bearing decaquaternary chain and deca-tertiary-amino groups that facilitates electron-transfer reactions via the photoexcited fullerene. Addition of the harmless salt, potassium iodide (10 mM) potentiated the ultraviolet A (UVA) or white light-mediated killing of Gram-negative bacteria Acinetobacter baumannii, Gram-positive methicillin-resistant Staphylococcus aureus and fungal yeast Candida albicans by 1-2+ logs. Mouse model infected with bioluminescent Acinetobacter baumannii gave increased loss of bioluminescence when iodide (10 mM) was combined with LC16 and UVA/white light. The mechanism may involve photoinduced electron reduction of (1)(C60>)* or (3)(C60>)* by iodide producing I· or I2 followed by subsequent intermolecular electron-transfer events of (C60>)(-)· to produce reactive radicals.
BACKGROUND: Since the beginning of the conflicts in the Middle East, US Army physicians have note... more BACKGROUND: Since the beginning of the conflicts in the Middle East, US Army physicians have noted a high rate of multidrug-resistant Acinetobacter baumannii infections among US soldiers wounded and initially treated in Iraq. In this study, we investigated the use of ultraviolet C (UVC) light for prevention of multidrug-resistant A. baumannii wound infections using mouse models.
Background: Local microbial infections induced by multiple-drug-resistant bacteria in the orthope... more Background: Local microbial infections induced by multiple-drug-resistant bacteria in the orthopedic field can be intractable, therefore development of new therapeutic modalities is needed. Photodynamic therapy (PDT) is a promising alternative modality to antibiotics for intractable microbial infections, and we recently reported that PDT has the potential to accumulate neutrophils into the infected site which leads to resolution of the infection. PDT for cancer has long been known to be able to stimulate the innate and adaptive arms of the immune system.
Linezolid and vancomycin decrease the therapeutic effect of methylene blue-photodynamic therapy in a mouse model of MRSA bacterial arthritis
Photochemistry and Photobiology, 2013
We previously reported that photodynamic therapy (PDT) using intra-articular methylene blue (MB) ... more We previously reported that photodynamic therapy (PDT) using intra-articular methylene blue (MB) could be used to treat arthritis in mice caused by bioluminescent methicillin-resistant Staphylococcus aureus (MRSA) either in a therapeutic or in a preventative mode. PDT accumulated neutrophils into the mouse knee via activation of chemoattractants such as inflammatory cytokines or chemokines. In this study, we asked whether PDT combined with antibiotics used for MRSA could provide added benefit in controlling the infection. We compared MB-PDT alone, systemic administration of either linezolid (LZD) alone or vancomycin (VCM) alone or the combination of PDT with either LZD or VCM. Real-time noninvasive imaging was used to serially follow the progress of the infection. PDT alone was the most effective, whereas LZD alone was ineffective and VCM alone showed some benefit. Surprisingly the addition of LZD or VCM reduced the therapeutic effect of PDT alone (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Considering that PDT in this mouse model stimulates neutrophils to be antibacterial rather than actively killing the bacteria, we propose that LZD and VCM might inhibit the activation of inflammatory cytokines without eradicating the bacteria, and thereby reduce the therapeutic effect of PDT.
This article is a highlight of the study by Maclean et al. in this issue of Photochemistry and Ph... more This article is a highlight of the study by Maclean et al. in this issue of Photochemistry and Photobiology describing the sporicidal effects 405 nm visible light alone on endospores of the Clostridium and Bacillus genera. 1.73 kJ cm À2 was capable of reducing endospore colony-forming units by up to 4-log 10 . These findings have never been previously demonstrated and may be incorporated into decontamination methods that span medical, military and food preparatory applications.
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