Abstract

The development of drug carriers based in lipid nanoparticles (LNPs) aims toward the synthesis of non-toxic multifunctional nanovehicles that can bypass the immune system and allow specific site targeting, controlled release and complete degradation of the carrier components. Among label free techniques, Surface Plasmon Resonance (SPR) biosensing is a versatile tool to study LNPs in the field of nanotherapeutics research. SPR, widely used for the analysis of molecular interactions, is based on the immobilization of one of the interacting partners to the sensor surface, which can be easily achieved in the case of LNPs by hydrophobic attachment onto commercial lipid- capture sensor chips. In the last years SPR technology has emerged as an interesting strategy for studying molecular aspects of drug delivery that determines the efficacy of the nanotherapeutical such as LNPs' interactions with biological targets, with serum proteins and with tumor extracelullar matrix. Moreover, SPR has contributed to the obtention and characterization of LNPs, gathering information about the interplay between components of the formulations, their response to organic molecules and, more recently, the quantification and molecular characterization of exosomes. By the combination of available sensor platforms, assay quickness and straight forward platform adaptation for new carrier systems, SPR is becoming a high throughput technique for LNPs' characterization and analysis.

Highlights

  • Drug delivery has been improved over the years with continuous effort to develop new and more efficient carriers

  • Functional carboxylic groups are included in carboxymethyl dextran (CMD) or alginate coated commercial gold sensor chips or they can be obtained from bare sensor surfaces adequately covered with thiol SAMs (Table 1) based on the robust covalent bond that is established between S and Au (Vericat et al, 2010)

  • The observed reduction in protein adsorption as poly- ethylene glycol (PEG) densities in the nanovehicles increases agreed with theoretical predictions. These results suggest that Surface Plasmon Resonance (SPR) studies could contribute to establish the physical basis of the different interactions of Lipid-based nanoparticles (LNPs) with proteins and cells

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Summary

INTRODUCTION

Drug delivery has been improved over the years with continuous effort to develop new and more efficient carriers. Immunogenic properties can be exploited for targeting in virus-like particles (VLPs) that display effective cell entry properties due to their viral origin (Zdanowicz and Chroboczek, 2016; Rohovie et al, 2017) All these vesicles lack of long-term storage stability and, if taken orally, they suffer a rapid degradation by stomach pH, bile salts or intestinal enzymes (Selvamuthukumar and Velmurugan, 2012). These difficulties and the need of compatible largescale manufacturing lead to the development of solid lipid nanoparticles (SLNs) and, more recently, nanostructured lipid carriers (NLCs) (Naseri et al, 2015; Oner et al, 2020). The aim of this review is to outline the state of the art in SPR sensing of LNPs, describing its usefulness and challenges in the framework of drug delivery research

Principle
Measurement Data and Analysis
SURFACE PREPARATION STRATEGIES
Covalent Immobilization
Capturing Approaches
Hydrophobic Attachment
Physical Adsorption
APPLICATIONS OF SPR-BASED BIOSENSORS IN THE STUDY OF LNPs
LNPs’ Interactions Involved in Drug Delivery
Obtention and Characterization of LNPs’ Formulations
Quantification and Molecular
CONCLUSIONS
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