Shape Matters: Comprehensive Analysis of Star-Shaped Lipid Nanoparticles

Abstract

The research of lipid nanoparticles (LNPs) has been ongoing for more than three decades, and more research are still being carried out today. Being the first Food and Drug Administration (FDA)-approved nanomedicine, LNPs not only provide various advantages, but also display some unique properties. The unique lipid bilayer structure of LNPs allows it to encapsulate both fat-soluble and water-soluble molecules, hence enabling a wide range of possibilities for the delivery of therapeutic agents with different physical and chemical properties. The ultra-small size of some LNPs confers them the ability to cross the blood brain barrier (BBB), thus obtaining superiority in the treatment of diseases of the central nervous system (CNS). The ability of tumor targeting is one of the basic requirements to be an excellent delivery system, where the LNPs have to reach the interior of the tumor. Factors that influence tumor extravasation and the permeability of LNPs are size, surface charge, lipid composition, and shape. The effect of size, surface charge, and lipid composition on the cellular uptake of LNPs is no longer recent news, while increasing numbers of researchers are interested in the effect of shape on the uptake of LNPs and its consequential effects. In our study, we prepared three lipid nanostars (LNSs) by mixing phosphatidylcholine (PC) with different backbone lengths (C14:C4 or C16:C6 or C18:C8) at a 3:1 ratio. Although several star-shaped nanocarriers have been reported, these are the first reported star-shaped LNPs. These LNSs were proven to be safe, similar in size with their spherical controls (~100 nm), and stable at 37°C. The release rate of these LNSs are inversely related to the length of the lipid backbone. Most importantly, these LNSs exhibited greatly enhanced cellular uptake and in vivo tumor extravasation compared with their spherical controls. Based on the different uptake and pharmacokinetic characteristics displayed by these LNSs, numerous route formulations could be taken into consideration, such as via injection or transdermal patch. Due to their excellent cellular uptake and in vivo tumor accumulation, these LNSs show exciting potential for application in cancer therapy.

Solid Lipid Nanoparticles Based on Monosubstituted Pillar[5]arenes: Chemoselective Synthesis of Macrocycles and Their Supramolecular Self-Assembly

“…Today, a number of works are devoted to the synthesis of different shaped SLN [ 20 , 43 , 44 , 45 , 46 ]. It has been shown that the shape of SLN can change depending on the nature and size of the substituents in the molecule [ 20 , 46 ], the interaction of the solute with the solvent [ 43 ], and the loading of SLN with some substance [ 45 ]. In this work, we studied the influence of substituent nature in the structure of monosubstituted pillar[5]arenes on the size and stability of formed particles.…”

Nanoparticle-Mediated In Situ Molecular Reprogramming of Immune Checkpoint Interactions for Cancer Immunotherapy

“…The shape of the particles has likewise been shown to impact tumor uptake following i.v. administration, with star-shaped particles showing a higher uptake in tumors . However, what we understand of the EPR effect and passive tumor targeting is undergoing a radical shift with a growing body of evidence suggesting that a particulate nature alone is unsuitable for tumor targeting in the clinic .…”

Physical Enhancement? Nanocarrier? Current Progress in Transdermal Drug Delivery

“…Lipid nanoparticles have been used as an alternative TDDS for pharmaceutical drugs and cosmetic compounds since the early 1990s [ 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ]. A solid lipid nanoparticle (SLN) was prepared by the exchange of the liquid lipid oil of the emulsions by solid lipid, which remains at a solid-state at room temperature and body temperature [ 66 , 67 ].…”

“…The SLNs are useful for incorporating lipophilic, hydrophilic, and water-insoluble compounds owing to their structural characteristics. Nanostructured lipid carriers (NLC) are known as the second generation of lipid nanoparticles [ 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ]. A variety of amphiphilic molecules can be used to prepare NLC ranging from phospholipids to artificial surfactants.…”

“…In particular, microneedles have been actively investigated, and clinical trials of delivery of macromolecules such as insulin, parathyroid hormone, and influenza vaccines were currently performed. Recently, nanocarrier-based TDDS [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , …”