Assessment of lactoferrin-conjugated solid lipid nanoparticles for efficient targeting to the lung.

Satish Shilpi,Vishnoo Dayal Vimal,Vandana Soni

doi:10.1007/s40204-015-0037-z

Satish Shilpi, Vishnoo Dayal Vimal + Show 1 more

Open Access

https://doi.org/10.1007/s40204-015-0037-z

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Abstract

The aim of the present study was to develop a target oriented drug delivery system for the lungs. Lactoferrin (Lf)-coupled solid lipid nanoparticles (SLNs) bearing rifampicin was prepared by a solvent injection method. The prepared nanoparticles were characterized for shape, particle size, polydispersity and percentage drug entrapment. An optimized formulation was then studied for its in vivo performance in animals and to determine its targeting efficiency. It was observed that, upon coupling with Lf, the size of SLNs increased while the percent entrapment efficiency decreases. In in vitro release, determined by a dialysis technique, analysis showed that uncoupled SLNs exhibited higher drug release as compared to coupled SLNs. An in vivo biodistribution study shows 47.7 ±0.4 drug uptakes by the lungs, which was 3.05 times higher in comparison to uncoupled SLNs. These biodistribution studies are further supported by the fluorescence study that revealed enhanced uptake of Lf-coupled SLNs in the lung. From the presented results, it can be concluded that Lf-coupled SLNs enhanced drug uptake in the lung. Moreover, lactoferrin is an efficient molecule that can be used for targeting active agents directly to the lung.

Highlights

The success of novel drug delivery systems depends on the development of formulations that are capable of improving the therapeutic index of biologically active molecules by increasing their concentration at desired target sites or organs
The coupling of Lf with the solid lipid nanoparticles (SLNs) was performed via carbodiimide chemistry; the –CONH-(amide linkage) bond is formed between the –NH2 groups present on the surface of the SLNs and the –COOH group of the Lf
The size of the coupled formulation was found to be higher when compared to the uncoupled formulation, which could be due to the coupling of Lf on the surface of the SLN

Summary

Introduction

The success of novel drug delivery systems depends on the development of formulations that are capable of improving the therapeutic index of biologically active molecules by increasing their concentration at desired target sites or organs. It is well known that various novel carriers have been used for drug delivery to the lungs for the treatment of tuberculosis, for example, microparticle (Zhou et al 2005; Zhuang et al 2012) poly(lactic-co-glycolic acid) (PLGA) nanospheres (Tomoda et al 2005; Tomoda and Makino 2007), stealth liposomes (Deol and Khuller 1997), functionalized nanoparticles (Sharma et al 2004), and SLNs (Anisimova et al 2000; Pandey et al 2005; Pandey and Khuller 2005). Microparticles offer excellent aerodynamic properties and their large geometric size reduces their uptake by alveolar macrophages, making them a suitable carrier for sustained drug release in the lungs. Liposomes can be prepared with lipids endogenous to the lungs and are safe. Their composition can be adjusted to modulate drug release and they can encapsulate both hydrophilic and lipophilic compounds with high drug loading (Loira-Pastoriza et al 2014)

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