Evaluation of Nanolipoprotein Particles (NLPs) as an In Vivo Delivery Platform

Abstract

Nanoparticles hold great promise for the delivery of therapeutics, yet limitations remain with regards to the use of these nanosystems for efficient long-lasting targeted delivery of therapeutics, including imparting functionality to the platform, in vivo stability, drug entrapment efficiency and toxicity. To begin to address these limitations, we evaluated the functionality, stability, cytotoxicity, toxicity, immunogenicity and in vivo biodistribution of nanolipoprotein particles (NLPs), which are mimetics of naturally occurring high-density lipoproteins (HDLs). We found that a wide range of molecules could be reliably conjugated to the NLP, including proteins, single-stranded DNA, and small molecules. The NLP was also found to be relatively stable in complex biological fluids and displayed no cytotoxicity in vitro at doses as high as 320 µg/ml. In addition, we observed that in vivo administration of the NLP daily for 14 consecutive days did not induce significant weight loss or result in lesions on excised organs. Furthermore, the NLPs did not display overt immunogenicity with respect to antibody generation. Finally, the biodistribution of the NLP in vivo was found to be highly dependent on the route of administration, where intranasal administration resulted in prolonged retention in the lung tissue. Although only a select number of NLP compositions were evaluated, the findings of this study suggest that the NLP platform holds promise for use as both a targeted and non-targeted in vivo delivery vehicle for a range of therapeutics.

Targeting the SR-B1 Receptor as a Gateway for Cancer Therapy and Imaging

“…The valrubicin/rHDL formulation was also found to have reduced toxicity toward non-malignant cells, demonstrating the selective tumor delivery capabilities of rHDL nanoparticles. In the past 10 years, scientists are realizing the potential of HDL and HDL mimetic drug delivery strategies in cancer theranostics, primarily due to the interaction of these nanoparticles ( Figure 1 ) with the SR-B1 receptor (McMahon et al, 2011; Jia et al, 2012; Rui et al, 2013; Zheng et al, 2013; Dong et al, 2014; Fischer et al, 2014). …”

Structure and Dynamics of Phospholipid Nanodiscs from All-Atom and Coarse-Grained Simulations

“…Furthermore, NDs as biocompatible drug carriers have been in the focus of pharmaceutical applications. 22 Most experimental studies of NDs focused on the properties of the MSPs as well as embedded membrane proteins. 2,4,5 Less is known about the detailed properties of the lipids in NDs.…”

Lipoproteins and lipoprotein mimetics for imaging and drug delivery

“…They are also highly biocompatible, biodegradable and non-immunogenic. [89] Next, it has been shown that lipoproteins can be re-routed to other targets via attachment of additional ligands to the apolipoprotein component[43] or the lipid coating. [90] Lipoproteins are also versatile, in that they can carry hydrophobic, lipophilic or hydrophilic payloads.…”

“…Another study, using iron oxide core HDL, also showed that intraperitoneal injection was viable to perform imaging with HDL-based agents. [124] This indicates that use of these agents may be streamlined by use of via intraperitoneal injections,[89] which is more straightforward than intravenous injection.…”