Chloramphenicol encapsulated in poly-ε-caprolactone–pluronic composite: nanoparticles for treatment of MRSA-infected burn wounds
Sanjeeb Kalita,1 Banasmita Devi,1 Raghuram Kandimalla,1 Kaustav Kalyan Sharma,1 Arup Sharma,2 Kasturi Kalita,3 Amal Chandra Kataki,4 Jibon Kotoky1 1Institute of Advanced Study in Science and Technology (IASST), Division of Life Sciences, Paschim Boragaon, Garchuk, Guwahati, Assam, India; 2College o...
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Dove Medical Press
2015
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oai:doaj.org-article:d6ec3f90b7124aab8749972fa8d280d62021-12-02T01:04:56ZChloramphenicol encapsulated in poly-ε-caprolactone–pluronic composite: nanoparticles for treatment of MRSA-infected burn wounds1178-2013https://doaj.org/article/d6ec3f90b7124aab8749972fa8d280d62015-04-01T00:00:00Zhttp://www.dovepress.com/chloramphenicol-encapsulated-in-poly-epsilon-caprolactonendashpluronic-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Sanjeeb Kalita,1 Banasmita Devi,1 Raghuram Kandimalla,1 Kaustav Kalyan Sharma,1 Arup Sharma,2 Kasturi Kalita,3 Amal Chandra Kataki,4 Jibon Kotoky1 1Institute of Advanced Study in Science and Technology (IASST), Division of Life Sciences, Paschim Boragaon, Garchuk, Guwahati, Assam, India; 2College of Veterinary Science, Assam Agriculture University, Khanapara, Guwahati, Assam, India; 3Hyat Hospital, Lalganesh, Guwahati, Assam, India; 4Dr B Borooah Cancer Institute, Guwahati, Assam, India Abstract: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) infection has increased precipitously over the past several decades, with far-reaching health care and societal costs. MRSA infections in the context of burn wounds lead to invasive disease that could potentially cause mortality. Chloramphenicol is a well-known broad-spectrum bacteriostatic antibiotic that has been used since 1949, but due to its hydrophobicity, poor penetration in skin, fast degradation, and toxicity, its application has been hindered. Furthermore, it has been demonstrated that old antibiotics such as chloramphenicol remained active against a large number of currently prevalent resistant bacterial isolates due to their low-level use in the past. Recently, the novel nanoparticulate drug-delivery system has been used and reported to be exceptionally useful for topical therapeutics, due to its distinctive physical characteristics such as a high surface-to-volume ratio and minuscule size. It helps to achieve better hydrophilicity, bioavailability, and controlled delivery with enhanced therapeutic index, which has resulted in decreased toxicity levels compared to the crude drug. Here, we report a novel chloramphenicol loaded with poly(ε-caprolactone) (PCL)-pluronic composite nanoparticles (CAM-PCL-P NPs), physicochemical characterizations, and its bioactivity evaluation in a MRSA-infected burn-wound animal model. CAM-PCL-P NPs could encapsulate 98.3% of the drug in the nanoparticles and release 81% of the encapsulated drug over 36 days with a time to 50% drug release of 72 hours (51%). Nanoparticle suspensions maintained the initial properties with respect to size and encapsulation efficiency, even after 6 months of storage at 4°C and 25°C, respectively (P>0.05). Significant reduction in the level of toxicity was observed for CAM-PCL-P NPs compared with that of free drug as confirmed from hemolytic activity against human blood erythrocytes and cytotoxicity assay against an MCF-7 breast cancer cell line. In vitro antibacterial activities were performed by zone of inhibition, minimum inhibitory concentrations, minimum bacterial concentration, and time-kill assays, which showed that CAM-PCL-P NPs exhibited significantly enhanced anti-MRSA activity against ten clinical isolates of MRSA strains. The augmented activity of CAM-PCL-P NPs was further tested on a MRSA-infected burn-wound animal model and achieved quicker efficacy in MRSA clearance and improved the survival rate compared with free-chloramphenicol treatment. Thus, we propose CAM-PCL-P NPs as a promising novel antimicrobial candidate that may have a good potential for preclinical applications. Keywords: chloramphenicol, PCL-pluronic, nanoparticle, methicillin-resistant Staphylococcus aureus, anti-MRSA activity, burn-wound animal modelKalita SDevi BKandimalla RSharma KKSharma AKalita KKataki ACKotoky JDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 2971-2984 (2015) |
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Medicine (General) R5-920 |
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Medicine (General) R5-920 Kalita S Devi B Kandimalla R Sharma KK Sharma A Kalita K Kataki AC Kotoky J Chloramphenicol encapsulated in poly-ε-caprolactone–pluronic composite: nanoparticles for treatment of MRSA-infected burn wounds |
| description |
Sanjeeb Kalita,1 Banasmita Devi,1 Raghuram Kandimalla,1 Kaustav Kalyan Sharma,1 Arup Sharma,2 Kasturi Kalita,3 Amal Chandra Kataki,4 Jibon Kotoky1 1Institute of Advanced Study in Science and Technology (IASST), Division of Life Sciences, Paschim Boragaon, Garchuk, Guwahati, Assam, India; 2College of Veterinary Science, Assam Agriculture University, Khanapara, Guwahati, Assam, India; 3Hyat Hospital, Lalganesh, Guwahati, Assam, India; 4Dr B Borooah Cancer Institute, Guwahati, Assam, India Abstract: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) infection has increased precipitously over the past several decades, with far-reaching health care and societal costs. MRSA infections in the context of burn wounds lead to invasive disease that could potentially cause mortality. Chloramphenicol is a well-known broad-spectrum bacteriostatic antibiotic that has been used since 1949, but due to its hydrophobicity, poor penetration in skin, fast degradation, and toxicity, its application has been hindered. Furthermore, it has been demonstrated that old antibiotics such as chloramphenicol remained active against a large number of currently prevalent resistant bacterial isolates due to their low-level use in the past. Recently, the novel nanoparticulate drug-delivery system has been used and reported to be exceptionally useful for topical therapeutics, due to its distinctive physical characteristics such as a high surface-to-volume ratio and minuscule size. It helps to achieve better hydrophilicity, bioavailability, and controlled delivery with enhanced therapeutic index, which has resulted in decreased toxicity levels compared to the crude drug. Here, we report a novel chloramphenicol loaded with poly(ε-caprolactone) (PCL)-pluronic composite nanoparticles (CAM-PCL-P NPs), physicochemical characterizations, and its bioactivity evaluation in a MRSA-infected burn-wound animal model. CAM-PCL-P NPs could encapsulate 98.3% of the drug in the nanoparticles and release 81% of the encapsulated drug over 36 days with a time to 50% drug release of 72 hours (51%). Nanoparticle suspensions maintained the initial properties with respect to size and encapsulation efficiency, even after 6 months of storage at 4°C and 25°C, respectively (P>0.05). Significant reduction in the level of toxicity was observed for CAM-PCL-P NPs compared with that of free drug as confirmed from hemolytic activity against human blood erythrocytes and cytotoxicity assay against an MCF-7 breast cancer cell line. In vitro antibacterial activities were performed by zone of inhibition, minimum inhibitory concentrations, minimum bacterial concentration, and time-kill assays, which showed that CAM-PCL-P NPs exhibited significantly enhanced anti-MRSA activity against ten clinical isolates of MRSA strains. The augmented activity of CAM-PCL-P NPs was further tested on a MRSA-infected burn-wound animal model and achieved quicker efficacy in MRSA clearance and improved the survival rate compared with free-chloramphenicol treatment. Thus, we propose CAM-PCL-P NPs as a promising novel antimicrobial candidate that may have a good potential for preclinical applications. Keywords: chloramphenicol, PCL-pluronic, nanoparticle, methicillin-resistant Staphylococcus aureus, anti-MRSA activity, burn-wound animal model |
| format |
article |
| author |
Kalita S Devi B Kandimalla R Sharma KK Sharma A Kalita K Kataki AC Kotoky J |
| author_facet |
Kalita S Devi B Kandimalla R Sharma KK Sharma A Kalita K Kataki AC Kotoky J |
| author_sort |
Kalita S |
| title |
Chloramphenicol encapsulated in poly-ε-caprolactone–pluronic composite: nanoparticles for treatment of MRSA-infected burn wounds |
| title_short |
Chloramphenicol encapsulated in poly-ε-caprolactone–pluronic composite: nanoparticles for treatment of MRSA-infected burn wounds |
| title_full |
Chloramphenicol encapsulated in poly-ε-caprolactone–pluronic composite: nanoparticles for treatment of MRSA-infected burn wounds |
| title_fullStr |
Chloramphenicol encapsulated in poly-ε-caprolactone–pluronic composite: nanoparticles for treatment of MRSA-infected burn wounds |
| title_full_unstemmed |
Chloramphenicol encapsulated in poly-ε-caprolactone–pluronic composite: nanoparticles for treatment of MRSA-infected burn wounds |
| title_sort |
chloramphenicol encapsulated in poly-ε-caprolactone–pluronic composite: nanoparticles for treatment of mrsa-infected burn wounds |
| publisher |
Dove Medical Press |
| publishDate |
2015 |
| url |
https://doaj.org/article/d6ec3f90b7124aab8749972fa8d280d6 |
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