Title:Formulation and Optimization of Solid Lipid Nanoparticle-based
Gel for Dermal Delivery of Linezolid using Taguchi Design
Volume: 19
Issue: 4
Author(s): Iti Chauhan*Lubhan Singh
Affiliation:
- Department of Pharmacy, Kharvel Subharti College of Pharmacy, Swami Vivekanand Subharti
University, Meerut, India
- Department of Pharmaceutics, I.T.S College of Pharmacy, Muradnagar,
Ghaziabad, India
Keywords:
Solid lipid nanoparticle, linezolid, skin and soft tissue infection, dermal delivery, taguchi design, tape-stripped skin infection model.
Abstract:
Background: Linezolid (LNZ) is a synthetic oxazolidinone antibiotic approved
for the treatment of uncomplicated and complicated skin and soft tissue infections caused
by gram-positive bacteria. Typically, LNZ is administered orally or intravenously in most
cases. However, prolonged therapy is associated with various side effects and lifethreatening
complications. Cutaneous application of LNZ will assist in reducing the dose,
hence minimizing the unwanted side/adverse effects associated with oral administration.
Dermal delivery provides an alternative route of administration, facilitating a local and sustained
concentration of the antimicrobial at the site of infection.
Objective: The current research work aimed to formulate solid lipid nanoparticles (SLNs)
based gel for dermal delivery of LNZ in the management of uncomplicated skin and soft
tissue infections to maximise its benefits and minimise the side effects.
Methods: SLNs were prepared by high-shear homogenisation and ultrasound method using
Dynasan 114 as solid lipid and Pluronic F-68 as surfactant. The effect of surfactant concentration,
drug-to-lipid ratio, and sonication time was investigated on particle size, zeta
potential, and entrapment efficiency using the Taguchi design. The main effect plot of
means and signal-to-noise ratio were generated to determine the optimized formulation.
The optimized batch was formulated into a gel, and ex vivo permeation study, in vitro and
in vivo antibacterial activity were conducted.
Results: The optimised process parameters to achieve results were 2% surfactant concentration,
a drug-to-lipid ratio of 1:2, and 360 s of sonication time. The optimized batch was
206.3± 0.17nm in size with a surface charge of -24.4± 4.67mV and entrapment efficiency
of 80.90 ± 0.45%. SLN-based gel demonstrated anomalous transport with an 85.43% in
vitro drug release. The gel showed a 5.03 ± 0.15 cm zone of inhibition while evaluated for
in vitro antibacterial activity against Staphylococcus aureus. Ex vivo skin permeation studies
demonstrated 20.308% drug permeation and 54.96% cutaneous deposition. In-vivo results
showed a significant reduction in colony-forming units in the group treated with LNZ
SLN-based gel.
Conclusion: Ex vivo studies ascertain the presence of the drug at the desired site and improve
therapy. In vivo results demonstrated the ability of SLN-based gel to significantly
reduce the number of bacteria in the stripped infection model. The utilization of SLN as an
LNZ carrier holds significant promise in dermal delivery.
