Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines

Abstract

COVID-19 vaccines have been developed with unprecedented speed which would not have been possible without decades of fundamental research on delivery nanotechnology. Lipid-based nanoparticles have played a pivotal role in the successes of COVID-19 vaccines and many other nanomedicines, such as Doxil® and Onpattro®, and have therefore been considered as the frontrunner in nanoscale drug delivery systems. In this review, we aim to highlight the progress in the development of these lipid nanoparticles for various applications, ranging from cancer nanomedicines to COVID-19 vaccines. The lipid-based nanoparticles discussed in this review are liposomes, niosomes, transfersomes, solid lipid nanoparticles, and nanostructured lipid carriers. We particularly focus on the innovations that have obtained regulatory approval or that are in clinical trials. We also discuss the physicochemical properties required for specific applications, highlight the differences in requirements for the delivery of different cargos, and introduce current challenges that need further development. This review serves as a useful guideline for designing new lipid nanoparticles for both preventative and therapeutic vaccines including immunotherapies.

Incorporation of Antibiotics into Solid Lipid Nanoparticles: A Promising Approach to Reduce Antibiotic Resistance Emergence

“…Different nanoparticles can be obtained composed of biocompatible and biodegradable lipids: liposomes, nanostructured lipid carriers or solid lipid nanoparticles, for instance. Liposomes have been the most applied lipid-based drug delivery systems, and they have also been approved for clinical treatments [ 32 ]. Nonetheless, they present a low capacity to encapsulate hydrophobic molecules, low storage stability and eventual drug leakage in the media [ 31 , 32 ].…”

“…Moreover, they present a versatile and stable alternative to liposomes, as they present good loading capacity for both hydrophobic and hydrophilic drugs. These characteristics make SLNs suitable DDSs for antibiotic drug delivery systems, as they present good permeation through biological barriers, good cell uptake, and they can be administrated through different routes [ 31 , 32 ]…”

“…Although different physicochemical characteristics can be evaluated, size, polydispersity and surface charge are the most relevant characteristics as they can define cell uptake, biodistribution or toxicity in vivo [ 32 ].…”

Non-Immunotherapy Application of LNP-mRNA: Maximizing Efficacy and Safety

“…Preclinical studies examining the basis of mRNA technology started already 30 years ago, with the first demonstration by Wolff et al showing that naked IVT mRNA injected into mice can be translated [ 7 ]. Recently, a number of LNP-mRNA vaccines for infectious diseases, mRNA-based cancer immunotherapies, and several RNA protein replacement therapeutics entered clinical trials [ 5 , 8 ]. In December 2020, LNP-mRNA vaccines against SARS-CoV-2 from BioNTech/Pfizer and Moderna were demonstrated to be highly effective and safe in a Phase 3 clinical trial in preventing symptomatic COVID-19, thereby obtaining emergency use authorizations or conditional marketing authorizations in several countries worldwide, giving hope for an end of the COVID-19 pandemic [ 9 , 10 , 11 ].…”

Use of nanotechnology in combating coronavirus

“…However, there are associated demerits as well which include problems during large-scale production, high cost and requirement of booster doses for development of required immunity levels (Bouazzaoui et al 2021 ). These disadvantages have been overcome using mRNA-based vaccines developed by Pfizer/BioNTech/Fosun Pharma (mRNA-BNT162b2/Comirnaty) and Moderna/US NIAID (mRNA-1273) which were approved for EUA due to its efficiency in maintaining mRNA stability as well as high levels of targeted delivery in the host cell (Thi et al 2021 ). These mRNA-based vaccines have used lipid nanoparticles as carrier molecules thus underlining the importance of nanotechnology in vaccine development.…”