Albumin coupled lipid nanoemulsions of diclofenac for targeted delivery to inflammation

Diclofenac lipid nanoemulsions (DLNEs) were prepared with different compositions. Based on size, PDI, zeta potential, and in vitro drug release, the optimized DLNEs (DLNE-4 and DLNE-7) were developed and evaluated for drug content, entrapment efficiencies, and stability in comparison to the control formulation (DLNE-1). The albumin was coupled to DLNE-7 globules (DLNE-8) by water soluble carbodiimide (EDC) method, purified, and quantified by modified Bradford method. The pharmacokinetic study was conducted in inflammation (granuloma air pouch model) induced rats. The maximum peak concentration of DLNE-8 was almost fourfold to fivefold in comparison to drug solution in granuloma air pouch fluid (GAPF). The therapeutic availability (TA) of DLNE-8 was 2.89, 2.34, and 1.66 times that of drug solution, DLNE-4 and DLNE-7, respectively. The GAPF/serum ratio of diclofenac from DLNE-8 was above one at all time points indicating the targeting potential of albumin ligated LNEs to inflammatory sites.From the Clinical EditorThis study demonstrates targeted delivery of diclofenac to an inflammatory environment using the granuloma air pouch model and diclofenac nanoemulsions with different compositions.

Graphical AbstractDiclofenac lipid nanoemulsions (DLNEs) were prepared with different compositions. Optimized formulations were developed based on size, PDI, zeta potential, and in vitro drug release. The optimized DLNEs were evaluated for drug content and entrapment efficiencies and stability. The albumin was coupled to DLNE-7 globules by EDC method and quantified by modified Bradford method. Granuloma air pouch was developed in rats to study in vivo pharmacokinetics. The rate and extent of absorption of diclofenac from albumin coupled LNE (DLNE-8) in granuloma air pouch fluid was higher than that of all other formulations indicating the preferential accumulation of drug at inflammatory site.Figure optionsDownload high-quality image (201 K)Download as PowerPoint slide