Multifunctional lipid-based nanocarriers with antibacterial and anti‐inflammatory activities for treating MRSA bacteremia in mice
Abstract Background Bacteremia-induced sepsis is a leading cause of mortality in intensive care units. To control a bacterial infection, an immune response is required, but this response might contribute to organ failure. Kidneys are one of the main organs affected by bacteremia. Combination therapi...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-02-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-021-00789-5 |
| _version_ | 1798034122940088320 |
|---|---|
| author | Chia-Chih Liao Huang-Ping Yu Shih-Chun Yang Ahmed Alalaiwe You-Shan Dai Fu-Chao Liu Jia-You Fang |
| author_facet | Chia-Chih Liao Huang-Ping Yu Shih-Chun Yang Ahmed Alalaiwe You-Shan Dai Fu-Chao Liu Jia-You Fang |
| author_sort | Chia-Chih Liao |
| collection | DOAJ |
| description | Abstract Background Bacteremia-induced sepsis is a leading cause of mortality in intensive care units. To control a bacterial infection, an immune response is required, but this response might contribute to organ failure. Kidneys are one of the main organs affected by bacteremia. Combination therapies with antibacterial and anti-inflammatory effects may be beneficial in treating bacteremia. This study aimed to develop nanostructured lipid carriers (NLCs) loaded with ciprofloxacin and rolipram that exert a combination of anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-inflammatory effects. Retinol was incorporated into the nanoparticles to transport retinol-binding protein 4 (RBP4) to the kidneys, which abundantly express RBP receptors. The NLCs were fabricated by high-shear homogenization and sonication, and neutrophils were used as a model to assess their anti-inflammatory effects. Mice were injected with MRSA to establish a model of bacteremia with organ injury. Results The mean nanoparticle size and zeta potential of the NLCs were 171 nm and − 39 mV, respectively. Ciprofloxacin (0.05%, w/v) and rolipram (0.02%) achieved encapsulation percentages of 88% and 96%, respectively, in the nanosystems. The minimum bactericidal concentration of free ciprofloxacin against MRSA increased from 1.95 to 15.63 µg/ml when combined with rolipram, indicating a possible drug-drug interaction that reduced the antibacterial effect. Nanoparticle inclusion promoted the anti-MRSA activity of ciprofloxacin according to time-kill curves. The NLCs were found to be largely internalized into neutrophils and exhibited superior superoxide anion inhibition than free drugs. Retinol incorporation into the nanocarriers facilitated their efficient targeting to the kidneys. The NLCs significantly mitigated MRSA burden and elastase distribution in the organs of MRSA-infected animals, and the greatest inhibition was observed in the kidneys. Bacterial clearance and neutrophil infiltration suppression attenuated the bacteremia-induced cytokine overexpression, leading to an improvement in the survival rate from 22% to 67%. Conclusions The dual role of our NLCs endowed them with greater efficacy in treating MRSA bacteremia than that of free drugs. |
| first_indexed | 2024-04-11T20:39:55Z |
| format | Article |
| id | doaj.art-7c18706c95e346a29fb1d3241bd049bb |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T20:39:55Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-7c18706c95e346a29fb1d3241bd049bb2022-12-22T04:04:15ZengBMCJournal of Nanobiotechnology1477-31552021-02-0119111810.1186/s12951-021-00789-5Multifunctional lipid-based nanocarriers with antibacterial and anti‐inflammatory activities for treating MRSA bacteremia in miceChia-Chih Liao0Huang-Ping Yu1Shih-Chun Yang2Ahmed Alalaiwe3You-Shan Dai4Fu-Chao Liu5Jia-You Fang6Department of Anesthesiology, Chang Gung Memorial HospitalDepartment of Anesthesiology, Chang Gung Memorial HospitalDepartment of Cosmetic Science, Providence UniversityDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz UniversityPharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung UniversityDepartment of Anesthesiology, Chang Gung Memorial HospitalDepartment of Anesthesiology, Chang Gung Memorial HospitalAbstract Background Bacteremia-induced sepsis is a leading cause of mortality in intensive care units. To control a bacterial infection, an immune response is required, but this response might contribute to organ failure. Kidneys are one of the main organs affected by bacteremia. Combination therapies with antibacterial and anti-inflammatory effects may be beneficial in treating bacteremia. This study aimed to develop nanostructured lipid carriers (NLCs) loaded with ciprofloxacin and rolipram that exert a combination of anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-inflammatory effects. Retinol was incorporated into the nanoparticles to transport retinol-binding protein 4 (RBP4) to the kidneys, which abundantly express RBP receptors. The NLCs were fabricated by high-shear homogenization and sonication, and neutrophils were used as a model to assess their anti-inflammatory effects. Mice were injected with MRSA to establish a model of bacteremia with organ injury. Results The mean nanoparticle size and zeta potential of the NLCs were 171 nm and − 39 mV, respectively. Ciprofloxacin (0.05%, w/v) and rolipram (0.02%) achieved encapsulation percentages of 88% and 96%, respectively, in the nanosystems. The minimum bactericidal concentration of free ciprofloxacin against MRSA increased from 1.95 to 15.63 µg/ml when combined with rolipram, indicating a possible drug-drug interaction that reduced the antibacterial effect. Nanoparticle inclusion promoted the anti-MRSA activity of ciprofloxacin according to time-kill curves. The NLCs were found to be largely internalized into neutrophils and exhibited superior superoxide anion inhibition than free drugs. Retinol incorporation into the nanocarriers facilitated their efficient targeting to the kidneys. The NLCs significantly mitigated MRSA burden and elastase distribution in the organs of MRSA-infected animals, and the greatest inhibition was observed in the kidneys. Bacterial clearance and neutrophil infiltration suppression attenuated the bacteremia-induced cytokine overexpression, leading to an improvement in the survival rate from 22% to 67%. Conclusions The dual role of our NLCs endowed them with greater efficacy in treating MRSA bacteremia than that of free drugs.https://doi.org/10.1186/s12951-021-00789-5Nanostructured lipid carriersCiprofloxacinRolipramBacteremiaMethicillin‐resistant Staphylococcus aureusSepsis |
| spellingShingle | Chia-Chih Liao Huang-Ping Yu Shih-Chun Yang Ahmed Alalaiwe You-Shan Dai Fu-Chao Liu Jia-You Fang Multifunctional lipid-based nanocarriers with antibacterial and anti‐inflammatory activities for treating MRSA bacteremia in mice Journal of Nanobiotechnology Nanostructured lipid carriers Ciprofloxacin Rolipram Bacteremia Methicillin‐resistant Staphylococcus aureus Sepsis |
| title | Multifunctional lipid-based nanocarriers with antibacterial and anti‐inflammatory activities for treating MRSA bacteremia in mice |
| title_full | Multifunctional lipid-based nanocarriers with antibacterial and anti‐inflammatory activities for treating MRSA bacteremia in mice |
| title_fullStr | Multifunctional lipid-based nanocarriers with antibacterial and anti‐inflammatory activities for treating MRSA bacteremia in mice |
| title_full_unstemmed | Multifunctional lipid-based nanocarriers with antibacterial and anti‐inflammatory activities for treating MRSA bacteremia in mice |
| title_short | Multifunctional lipid-based nanocarriers with antibacterial and anti‐inflammatory activities for treating MRSA bacteremia in mice |
| title_sort | multifunctional lipid based nanocarriers with antibacterial and anti inflammatory activities for treating mrsa bacteremia in mice |
| topic | Nanostructured lipid carriers Ciprofloxacin Rolipram Bacteremia Methicillin‐resistant Staphylococcus aureus Sepsis |
| url | https://doi.org/10.1186/s12951-021-00789-5 |
| work_keys_str_mv | AT chiachihliao multifunctionallipidbasednanocarrierswithantibacterialandantiinflammatoryactivitiesfortreatingmrsabacteremiainmice AT huangpingyu multifunctionallipidbasednanocarrierswithantibacterialandantiinflammatoryactivitiesfortreatingmrsabacteremiainmice AT shihchunyang multifunctionallipidbasednanocarrierswithantibacterialandantiinflammatoryactivitiesfortreatingmrsabacteremiainmice AT ahmedalalaiwe multifunctionallipidbasednanocarrierswithantibacterialandantiinflammatoryactivitiesfortreatingmrsabacteremiainmice AT youshandai multifunctionallipidbasednanocarrierswithantibacterialandantiinflammatoryactivitiesfortreatingmrsabacteremiainmice AT fuchaoliu multifunctionallipidbasednanocarrierswithantibacterialandantiinflammatoryactivitiesfortreatingmrsabacteremiainmice AT jiayoufang multifunctionallipidbasednanocarrierswithantibacterialandantiinflammatoryactivitiesfortreatingmrsabacteremiainmice |