Major difference in particle size, minor difference in release profile: a case study of solid lipid nanoparticles.

Solid lipid nanoparticles (SLN) have been widely used in a variety of drug delivery routes, which have the outstanding advantage of controlled drug release. The release of SLN is dominated by many factors, among which the particle size of SLN is a critical one. The aim of this project was to explore the relationship between drug release profile and particle size of SLN. SLN were synthesized via the hot high-pressure homogenization (HPH) method, budesonide (BUD) was used as the model drug, and BUD-SLN1-BUD-SLN4 with increasing particle size was obtained, i.e. 120, 240, 360, and 480 nm. The prepared SLN has good encapsulation efficiency, drug loading capacity, and stability. In vitro release behavior studies showed that the cumulative release of BUD-SLN in Tris-Maleate (Tris-M) media was negligible, while that in Tris-M plus pancreatin media or Tris-M-ethanol media obeyed Ritger-Peppas model or first-order kinetic model, respectively. Noticeably, the release behavior of SLN was to some extent related to the average particle size of SLN, but the correlation was insignificant when the intersection degree of particle size distribution was great. This study provides a new idea for the understanding of in vitro release of SLN and has a certain referencing value for the research and development of novel nanomedicines.

Nanostructure of DiR-Loaded Solid Lipid Nanoparticles with Potential Bioimaging Functions.

The fluorescence dye-loaded nanoparticles are widely used as bioimaging agents in the field of nanotheranostics. However, the nanoparticles for nanotheranostics usually consist of synthetic materials, such as metal, silica, and organic polymers, which are often biologically incompatible and may arouse toxicity issues. Herein, the potential of near-infrared probe DiR-containing solid lipid nanoparticle suspensions (DiR-SLNS) as the bioimaging agent, which was prepared by lipids and surfactants with excellent biocompatibility, was investigated in this study. The nanostructure of DIR-SLNS system and the distribution of DiR were studied by dissipative particle dynamics (DPD) simulations. The stability of physicochemical properties and fluorescence spectra of DIR-SLNS system were investigated using dynamic laser scattering (DLS), nanoparticle tracking analysis (NTA), and fluorescence spectra. The fluorescence intensity-concentration correlation of DIR-SLNS was also evaluated. As a result, DiR-SLNS demonstrated a "core-shell"-like nanostructure and DiR was mainly distributed in the cetyl palmitate (CP) core rather than the surface of SLNS, which was beneficial to its potential applications in bioimaging. DiR-SLNS exhibited remarkable physicochemical stability as the nanoparticles maintained ~ 90% fluorescence intensity during the 10-day storage time. The correlation between fluorescence intensity and concentration was established and validated using a linear regression model. This study proposed a type of promising candidates in nano-scale with higher safety and fluorescence stability for bioimaging.

Inhalable Biomineralized Liposomes for Cyclic Ca2+-Burst-Centered Endoplasmic Reticulum Stress Enhanced Lung Cancer Ferroptosis Therapy.

Lung cancer with the highest mortality poses a great threat to human health. Ferroptosis therapy has recently been raised as a promising strategy for lung cancer treatment by boosting the reactive species (ROS) production and lipid peroxidation (LPO) accumulation intracellularly. However, the insufficient intracellular ROS level and the unsatisfactory drug accumulation in lung cancer lesions hamper the efficacy of ferroptosis therapy. Here, an inhalable biomineralized liposome LDM co-loaded with dihydroartemisinin (DHA) and pH-responsive calcium phosphate (CaP) was constructed as a ferroptosis nanoinducer for achieving Ca2+-burst-centered endoplasmic reticulum (ER) stress enhanced lung cancer ferroptosis therapy. Equipped with excellent nebulization properties, about 6.80-fold higher lung lesions drug accumulation than intravenous injection made the proposed inhalable LDM an ideal nanoplatform for lung cancer treatment. The Fenton-like reaction mediated by DHA with peroxide bridge structure could contribute to intracellular ROS production and induce ferroptosis. Assisted by DHA-mediated sarco-/endoplasmic reticulum calcium ATPase (SERCA) inhibition, the initial Ca2+ burst caused by CaP shell degradation triggered the Ca2+-mediated intense ER stress and subsequently induced mitochondria dysfunction to further boost ROS accumulation, which strengthens ferroptosis. The second Ca2+ burst occurred as a result of Ca2+ influx through ferroptotic pores on cell membranes, thus sequentially constructing the lethal "Ca2+ burst-ER stress-ferroptosis" cycle. Consequently, the Ca2+-burst-centered ER stress enhanced ferroptosis process was confirmed as a cell swelling and cell membrane disruption process driven by notable intracellular ROS and LPO accumulation. The proposed LDM showed an encouraging lung retention property and extraordinary antitumor ability in an orthotropic lung tumor murine model. In conclusion, the constructed ferroptosis nanoinducer could be a potential tailored nanoplatform for nebulization-based pulmonary delivery and underscore the application of Ca2+-burst-centered ER stress enhanced lung cancer ferroptosis therapy.

Two different protein corona formation modes on Soluplus® nanomicelles.

Soluplus® nanomicelles have been widely reported in biomedical field for their excellent drug loading capacity and solubility enhancement ability. However, when administrated in vivo, the protein corona will be formed on Soluplus® nanomicelles, significantly affecting their drug delivery performance. Up to now, few studies examined the protein corona formation process and its impact factors of Soluplus® nanomicelles. The multiple proteins in biofluids may form protein corona in different modes due to their diversified properties. In this study, Bovine serum albumin (BSA), Lysozyme (Lyso) and Bovine hemoglobin (BHb) were chosen as model proteins to investigate the protein corona formation process of Soluplus® nanomicelles. By analyzing the polarity of the protein amino acid residues distributing microenvironments, the results showed that there were two different protein corona formation modes, i.e., surface adsorption and insertion, which were determined by the hydrophilicity of proteins. The hydrophobic BHb followed the insertion mode while hydrophilic BSA and Lyso followed the surface adsorption mode. Ultimately, upon protein corona formation, the size and surface chemistry of nanomicelles was significantly affected. We believe this study will provide a new research paradigm to the design and application of Soluplus® nanomicelles.