TY - JOUR
T1 - Unveiling the potential of nano-structured lipid carriers for oral administration of cefepime
T2 - Bioavailability and safety investigations
AU - Ghani, Shah Faisal
AU - Ali, Zakir
AU - Shah, Kifayat Ullah
AU - Mirza, Rashna
AU - Alamri, Ali H.
AU - Fatease, Adel Al
AU - Lahiq, Ahmed A.
AU - Alruwaili, Nabil K.
AU - Jin, Sung Giu
AU - ud Din, Fakhar
N1 - Publisher Copyright:
© 2025 Elsevier B.V.
PY - 2025/8/5
Y1 - 2025/8/5
N2 - Cefepime (CFPM) is a potent fourth-generation cephalosporin antibiotic primarily employed in the treatment of systemic infections. However, its poor intestinal permeability leads to low oral bioavailability thereby limiting its effectiveness. This study aimed to enhance CFPM oral bioavailability using nanostructured lipid carriers (NLCs). CFPM-loaded NLCs were prepared via the microemulsion technique, with optimization conducted using Design Expert® software to vary concentrations of Tween® 80, oleic acid, Compritol 888 ATO®, and CFPM. Physicochemical characterization through techniques like transmission electron microscopy (TEM), x-ray diffraction (XRD) and Fourier transform infrared (FTIR) were performed followed by in vitro release study, stability analysis, antimicrobial assay and in vivo pharmacokinetic investigations. Optimized NLCs showed size in nanometric range (174 nm), stable zeta potential (- 27 mV), and high entrapment efficiency (86 %). TEM analysis showed round morphology, XRD demonstrated amorphous nature and FTIR exhibited compatibility of the ingredients of CFPM-loaded NLCs. In vitro release studies demonstrated sustained drug release compared to CFPM solution, while antimicrobial efficacy via microbroth dilution method showed a 2-fold increase with CFPM-NLCs. Stability tests as per ICH guidelines revealed no significant changes in particle size, polydispersity index, or zeta potential after six months, indicating the formulation's stability. Pharmacokinetic evaluation exhibited significantly higher plasma concentrations and enhanced oral bioavailability (11-fold) with CFPM-NLCs compared to the drug solution. Acute oral toxicity studies confirmed the safety of CFPM-NLCs. These findings underscore the potential of CFPM-NLCs as an effective drug delivery system, offering sustained release, improved antimicrobial activity, and enhanced oral bioavailability, promising benefits for clinical applications.
AB - Cefepime (CFPM) is a potent fourth-generation cephalosporin antibiotic primarily employed in the treatment of systemic infections. However, its poor intestinal permeability leads to low oral bioavailability thereby limiting its effectiveness. This study aimed to enhance CFPM oral bioavailability using nanostructured lipid carriers (NLCs). CFPM-loaded NLCs were prepared via the microemulsion technique, with optimization conducted using Design Expert® software to vary concentrations of Tween® 80, oleic acid, Compritol 888 ATO®, and CFPM. Physicochemical characterization through techniques like transmission electron microscopy (TEM), x-ray diffraction (XRD) and Fourier transform infrared (FTIR) were performed followed by in vitro release study, stability analysis, antimicrobial assay and in vivo pharmacokinetic investigations. Optimized NLCs showed size in nanometric range (174 nm), stable zeta potential (- 27 mV), and high entrapment efficiency (86 %). TEM analysis showed round morphology, XRD demonstrated amorphous nature and FTIR exhibited compatibility of the ingredients of CFPM-loaded NLCs. In vitro release studies demonstrated sustained drug release compared to CFPM solution, while antimicrobial efficacy via microbroth dilution method showed a 2-fold increase with CFPM-NLCs. Stability tests as per ICH guidelines revealed no significant changes in particle size, polydispersity index, or zeta potential after six months, indicating the formulation's stability. Pharmacokinetic evaluation exhibited significantly higher plasma concentrations and enhanced oral bioavailability (11-fold) with CFPM-NLCs compared to the drug solution. Acute oral toxicity studies confirmed the safety of CFPM-NLCs. These findings underscore the potential of CFPM-NLCs as an effective drug delivery system, offering sustained release, improved antimicrobial activity, and enhanced oral bioavailability, promising benefits for clinical applications.
KW - Bioavailability
KW - Box-Behnken Design
KW - Cefepime
KW - Improved permeability
KW - Nanostructured lipid carriers
UR - https://www.scopus.com/pages/publications/105002659484
U2 - 10.1016/j.colsurfa.2025.136938
DO - 10.1016/j.colsurfa.2025.136938
M3 - Article
AN - SCOPUS:105002659484
SN - 0927-7757
VL - 718
JO - Colloids and Surfaces A: Physicochemical and Engineering Aspects
JF - Colloids and Surfaces A: Physicochemical and Engineering Aspects
M1 - 136938
ER -