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

Muhammad Asghar Khan,Abdelbary Elhissi,Muhammad Shahid,Mohsin Kazi,Muhammad Shafique,Muhammad Sohail,Zahid Hussain,Shafi Ullah Khan,Hnin Ei Thu,Sultan M Alshehri,Shahzeb Khan,Hajra Afeera Hamid,Mahwish Kamran,Muhammad Wasim

doi:10.3390/pharmaceutics13101632

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.

Highlights

In earlier centuries, infectious diseases triggered by numerous bacterial species were the primary cause of death [1]
Unloaded Lipid–Polymer Hybrid Nanoparticles (LPHNs) were prepared on the basis of three variables i.e., surfactant concentration, magnetic stirring time and sonication time
The key process and experimental conditions including concentrations of polymers and lipids, stirring rate, sonication and stirring time were optimized for stable LPHNs

Summary

Introduction

Infectious diseases triggered by numerous bacterial species were the primary cause of death [1]. Norfloxacin (NOR; Figure 1), a member of the FQs family, is a drug of choice for the diseases caused by Escherichia coli, vibriocholerae, shigella and campylobacter [4] It is prescribed globally for the treatment of gonorrhea, eye infections and urinary tract infections [5,6]. This hydrophobic nature exacerbates its global image and drives pharmaceutical scientists to place it in Class-IV of the Biopharmaceutical Classification System (BCS-IV), representing low solubility and low permeability [8,9] Various approaches, such as Solid Dispersion and Cyclodextrin inclusion complexes, have been used to improve the solubility and bioavailability of Norfloxacin [10,11]. There have been reports of some issues associated with the above approaches, which include scale up and physical stability [12,13]

Objectives

Methods

Results

Discussion

Conclusion