TY - JOUR
T1 - In vitro antibacterial activity and in vivo pharmacokinetics of intravenously administered Amikacin-loaded Liposomes for the management of bacterial septicaemia
AU - Maxwell, Amala
AU - Chaudhari, Bhim Bahadur
AU - Chaudhari, Pinal
AU - Ananthamurthy, Koteshwara
AU - Aranjani, Jesil
AU - Moorkoth, Sudheer
AU - Ghate, Vivek
AU - Lewis, Shaila
N1 - Funding Information:
The authors are grateful to the All-India Council for Technical Education (AICTE), New Delhi, India, for providing financial assistance in the form of the National Doctoral Fellowship (NDF) to Amala Maxwell [File No. 1–6190129051 ]. The authors also thank Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE), Manipal, India, for providing Intramural funds and facilities for the research. The authors acknowledge Simulations Plus, Lancaster, USA for providing academic license to access Gastroplus™.
Funding Information:
The authors are grateful to the All-India Council for Technical Education (AICTE), New Delhi, India, for providing financial assistance in the form of the National Doctoral Fellowship (NDF) to Amala Maxwell [File No. 1–6190129051]. The authors also thank Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE), Manipal, India, for providing Intramural funds and facilities for the research. The authors acknowledge Simulations Plus, Lancaster, USA for providing academic license to access Gastroplus™.
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/12
Y1 - 2022/12
N2 - Systemic delivery of amikacin is a widely adopted treatment modality for severe infections like sepsis. However, the current course of treatment requires repeated bolus doses of amikacin, prolonged hospitalization, and continuous therapeutic monitoring to manage the severe adverse effects. Amikacin has short half-life, which further challenges the delivery of sufficient systemic concentrations when administered by intravenous route. To solve this issue, novel delivery systems, amikacin liposomes (Ak-lip) were developed and evaluated for its antibacterial efficacy (agar plate diffusion and resazurin microtiter assay) and in vivo drug release in Sprague-Dawley rats. The Ak-lip were prepared by modified thin film hydration method and optimized based on particle size and Zeta potential. The zone of inhibition for Ak-lip and amikacin was found to be 22 mm and 26 mm against Staphylococcus aureus. The minimum inhibitory concentrations (MIC) of amikacin and Ak-lip against Staphylococcus aureus were found to be 3 µg/mL and 9 µg/mL, and for Pseudomonas aeruginosa were 0.6 µg/mL and 0.9 µg/mL respectively. The in vivo pharmacokinetic parameters were determined using Gastroplus™. A significant difference in the pharmacokinetic parameters (AUC, Cmax) was observed between amikacin and Ak-lip. The developed formulation showed good colloidal stability and sustained release profile up to 72 h which can reduce dosing frequency, minimize hospitalization and improve bactericidal activity at lower concentrations paving the path for improved therapeutic interventions in the treatment of sepsis.
AB - Systemic delivery of amikacin is a widely adopted treatment modality for severe infections like sepsis. However, the current course of treatment requires repeated bolus doses of amikacin, prolonged hospitalization, and continuous therapeutic monitoring to manage the severe adverse effects. Amikacin has short half-life, which further challenges the delivery of sufficient systemic concentrations when administered by intravenous route. To solve this issue, novel delivery systems, amikacin liposomes (Ak-lip) were developed and evaluated for its antibacterial efficacy (agar plate diffusion and resazurin microtiter assay) and in vivo drug release in Sprague-Dawley rats. The Ak-lip were prepared by modified thin film hydration method and optimized based on particle size and Zeta potential. The zone of inhibition for Ak-lip and amikacin was found to be 22 mm and 26 mm against Staphylococcus aureus. The minimum inhibitory concentrations (MIC) of amikacin and Ak-lip against Staphylococcus aureus were found to be 3 µg/mL and 9 µg/mL, and for Pseudomonas aeruginosa were 0.6 µg/mL and 0.9 µg/mL respectively. The in vivo pharmacokinetic parameters were determined using Gastroplus™. A significant difference in the pharmacokinetic parameters (AUC, Cmax) was observed between amikacin and Ak-lip. The developed formulation showed good colloidal stability and sustained release profile up to 72 h which can reduce dosing frequency, minimize hospitalization and improve bactericidal activity at lower concentrations paving the path for improved therapeutic interventions in the treatment of sepsis.
UR - http://www.scopus.com/inward/record.url?scp=85140711136&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85140711136&partnerID=8YFLogxK
U2 - 10.1016/j.colsurfb.2022.112892
DO - 10.1016/j.colsurfb.2022.112892
M3 - Article
C2 - 36219888
AN - SCOPUS:85140711136
VL - 220
JO - Colloids and Surfaces B: Biointerfaces
JF - Colloids and Surfaces B: Biointerfaces
SN - 0927-7765
M1 - 112892
ER -