Tadpole-Like Anisotropic Polymer/Lipid Janus Nanoparticles for Nose-to-Brain Drug Delivery: Importance of Geometry, Elasticity on Mucus-Penetration Ability

Abstract

Asymmetric geometry (aspect ratio >1), moderate stiffness (i.e., semielasticity), large surface area, and low mucoadhesion of nanoparticles are the main features to reach the brain by penetrating across the nasal mucosa. Herein, a new application has been presented for the use of multifunctional Janus nanoparticles (JNPs) with controllable geometry and size as a noseto-brain (N2B) delivery system by changing proportions of Precirol ATO 5 and polycaprolactone compartments and other operating conditions. To bring to light the N2B application of JNPs, the results are presented in comparison with polymer and solid lipid nanoparticles, which are frequently used in the literature regarding their biopharmaceutical aspects: mucoadhesion and permeability through the nasal mucosa. The morphology and geometry of JPs were observed via cryogenic-temperature transmission electron microscopy images, and their particle sizes were verified by dynamic light scattering, atomic force microscopy, and scanning electron microscopy. Although all NPs showed penetration across the mucus barrier, the best increase in penetration was observed with asymmetric and semielastic JNPs, which have low interaction ability with the mucus layer. This study presents a new and promising field of application for a multifunctional system suitable for N2B delivery, potentially benefiting the treatment of brain tumors and other central nervous system diseases.

Multi-Stimuli-Responsive Tadpole-like Polymer/Lipid Janus Microrobots for Advanced Smart Material Applications

“…The emulsion-solvent evaporation process represents a straightforward one-pot technique that is well-suited for the preparation of significant quantities of JMs from various polymers and other biodegradable materials. Moreover, this technique is easily scalable and requires minimal processing equipment. ,, The design parameters can be easily modified by using this method. Because the functions of micromotors depend on their geometry, controlling their shape is critical for many potential applications, and it can be controlled by adjusting the interfacial tensions between different phases. , For this purpose, the effect of the surfactant type in the external phase on the geometry of the JPs was systematically analyzed.…”

“…Previous studies in our group showed that the release profiles of hydrophilic and hydrophobic drugs were affected by the positions of the lipid compartment and the asymmetry. Hydrophilic drugs are released more rapidly from structures with a larger aspect ratio due to the elongation of the lipid compartment, while drug release occurs more slowly from structures with a smaller aspect ratio due to reduced surface area . On the other hand, while the polymer compartment offers a high hydrophobic drug loading capacity, the lipid compartment wraps around the polymer in a thin layer to ensure maximum drug molecule retention inside the polymer compartment. , …”

“…Polymer/lipid JM particles were prepared using the double emulsion solvent evaporation method. − The internal aqueous phase consisted of PPYNP dispersed in 0.5 mL of UP water. PPYNP-to-lipid mass ratios studied were ×0.5, ×1, and ×1.5 (w/w 0.06 for ×0.5).…”

“…From here, unlike the traditional delivery systems, Janus particles (JP) have attracted great interest in recent years in pioneering studies as biomedical robots due to their anisotropic geometry with unique compartments whose surfaces have two or more different physical properties within a single structure. − Over the past few decades, micro-/nano-Janus motors have evolved with significant improvements in manufacturing and driving, and external fields can propel them. Particularly, besides the chemical composition of JP, their precisely tunable shape is one of the most important design parameters to mimic nature as it will significantly affect their motion speed and even their directions in fluid environments. , The proportions of compartments and other processing conditions can be adjusted to change the shape of JPs from spherical to the anisotropic form. , Because of their intrinsic immiscibility, polymers and lipids are promising candidates for phase separation in the formation of JPs .…”

“…From here, unlike the traditional delivery systems, Janus particles (JP) have attracted great interest in recent years in pioneering studies as biomedical robots due to their anisotropic geometry with unique compartments whose surfaces have two or more different physical properties within a single structure. − Over the past few decades, micro-/nano-Janus motors have evolved with significant improvements in manufacturing and driving, and external fields can propel them. Particularly, besides the chemical composition of JP, their precisely tunable shape is one of the most important design parameters to mimic nature as it will significantly affect their motion speed and even their directions in fluid environments. , The proportions of compartments and other processing conditions can be adjusted to change the shape of JPs from spherical to the anisotropic form. , Because of their intrinsic immiscibility, polymers and lipids are promising candidates for phase separation in the formation of JPs . Despite the significant research efforts devoted to stimuli-responsive Janus micro-/nanomachines, multiresponsive, bioinspired, and organic material-based (polymer and lipid materials) JP that can be triggered by temperature and the magnetic field have never been studied. − Herein, this study aimed to construct biomimetic robots, which were prepared by a bottom-up approach that can simulate similar motions in biological microswimmers such as tadpoles, sperm, bacteria, and algae to enhance diffusivity through barriers and biological hydrogels due to their asymmetric geometry (aspect ratio >1).…”