An oral colon-targeted drug delivery system holds great potential in preventing systemic toxicity and preserving the therapeutic benefits of ulcerative colitis (UC) treatment. In this study, we developed a negatively charged PLGA-PEG nanoparticle system for encapsulating naringin (Nar). Additionally, chitosan and mannose were coated on the surface of these nanoparticles to enhance their mucosal adsorption and macrophage targeting abilities. The resulting nanoparticles, termed MC@Nar-NPs, exhibited excellent resistance against decomposition in the strong acidic gastrointestinal environment and specifically accumulated at inflammatory sites. Upon payload release, MC@Nar-NPs demonstrated remarkable efficacy in alleviating colon inflammation as evidenced by reduced levels of pro-inflammatory cytokines in both blood and colon tissues, as well as the scavenging of reactive oxygen species (ROS) in the colon. This oral nanoparticle delivery system represents a novel approach to treating UC by utilizing Chinese herbal ingredient-based oral delivery and provides a theoretical foundation for local and precise intervention in specific UC treatment.
Docetaxel (DTX) is one kind of well-known anticancer drugs against tumors. GDC0941 was used to inhibit PI3K/Akt signal pathway and improve anti-tumor activity. PLGA-PEG-R7 (poly lactic-co-glycolic acid polyethylene glycol bending with cell penetrating peptide R7)/poly sulfadimethoxine-Folate nanoparticles (R7/PSD-Fol NPs) were made to load DTX and GDC0941 simultaneously. In vitro, the release capacity of DTX and GDC0941 inside nanoparticles was determined and both drugs could release from nanoparticles to 70% within 48h. The result of flow cytometry showed that GDC0941 had no interference on cell uptake and R7/PSD-Fol NPs could enhance MCF-7 cells uptake the most significantly. In cell colony study, GDC0941 could further improve the anti-tumor effect of DTX and inhibit the formation of cell clones on the basis of enhancing the uptake of R7/PSD-Fol NPs. The capability of cell colony formation was as follows: DTX > DTX + GDC0941 > R7 NPs > R7/PSD-Fol NPs. The expression of cell apoptosis proteins treated with R7/PSD-Fol NPs was the lowest. The addition of GDC0941 could decrease the full-length content of apoptotic proteins caspase-3 and caspase-9. In vivo, pharmacokinetic parameters results showed us that GDC0941 had no interference on pharmacokinetic study. Main pharmacokinetic parameters of DTX suspension and R7/PSD-Folate NPs suspension showed significant differences.
Due to the high risk of tearing and rupture, vulnerable atherosclerotic plaques would induce serious cardiovascular and cerebrovascular diseases. Despite the available clinical methods can evaluate the vulnerability of plaques and specifically treat vulnerable plaques before a cardiovascular event, but the efficiency is still low and undesirable. Herein, we rationally design and engineer the low-intensity focused ultrasound (LIFU)-responsive [email protected] nanomedicine for the highly efficient treatment of vulnerable plaques by facilely loading phase transition agent perfluorohexane (PFH) into biocompatible PLGA-PEG-PLGA nanoparticles (PPP NPs) and then attaching dextran sulphate (DS) onto the surface of PPP NPs for targeting delivery. DS, as a typical macrophages-targeted molecule, can achieve the precise vaporization of NPs and subsequently controllable apoptosis of RAW 264.7 macrophages as induced by acoustic droplet vaporization (ADV) effect. In addition, the introduction of DiR and Fe 3 O 4 endows nanomedicine with near-infrared fluorescence (NIRF) and magnetic resonance (MR) imaging capabilities. The engineered [email protected] nanomedicine that uses macrophages as therapeutic targets achieve the conspicuous therapeutic effect of shrinking vulnerable plaques based on in vivo and in vitro evaluation outcomes. A reduction of 49.4% of vascular stenosis degree in gross pathology specimens were achieved throughout the treatment period. This specific, efficient and biosafe treatment modality potentiates the biomedical application in patients with cardiovascular and cerebrovascular diseases based on the relief of the plaque rupture concerns.
危险品化学品经营许可证（带存储）