Norfloxacin Loaded Lipid Polymer Hybrid Nanoparticles for Oral Administration: Fabrication, Characterization, In Silico Modelling and Toxicity Evaluation

Abstract

Norfloxacin (NOR), widely employed as an anti-bacterial drug, has poor oral bioavailability. Nano based drug delivery systems are widely used to overcome the existing oral bioavailability challenges. Lipid–Polymer Hybrid Nanoparticles (LPHNs) exhibit the distinctive advantages of both polymeric and liposomes nanoparticles, while excluding some of their disadvantages. In the current study, NOR loaded LPHNs were prepared, and were solid amorphous in nature, followed by in vitro and in vivo evaluation. The optimized process conditions resulted in LPHNs with the acceptable particle size 121.27 nm, Polydispersity Index (PDI) of 0.214 and zeta potential of −32 mv. The addition of a helper lipid, oleic acid, and polymers, ethyl cellulose, substantially increased the encapsulation efficiency (EE%) (65% to 97%). In vitro study showed a sustained drug release profile (75% within 12 h) for NOR LPHNs. The optimized NOR LPHNs showed a significant increase (p < 0.05) in bioavailability compared to the commercial product. From the acute toxicity study, the LD50 value was found to be greater than 1600 mg/kg. The molecular modelling studies substantiated the experimental results with the best combination of polymers and surfactants that produced highly stable LPHNs. Therefore, LPHNs proved to be a promising system for the delivery of NOR, as well as for other antibiotics and hydrophobic drugs.

Keywords

• lipid polymer hybrid nanoparticles
• norfloxacin
• acute toxicity
• oral bioavailability
• in silico modelling