Drug delivery nanoparticles for preventing implant bacterial infections based on the bacteria and immunity mechanisms.

Implant dysfunction and failure during medical treatment can be attributed to bacterial infection with Staphylococcus aureus and Enterococcus faecalis, which are the prevalent strains responsible for implant infections. Currently, antibiotics are primarily used either locally or systemically to prevent and treat bacterial infections in implants. However, the effectiveness of this approach is unsatisfactory. Therefore, the development of new antimicrobial medications is crucial to address the clinical challenges associated with implant infections. In this study, a nanoparticle (ICG+RSG) composed of indocyanine green (ICG) and rosiglitazone (RSG), and delivered using 1,2-dipalmitoyl-snglycero-3-phosphocholine (DPPC) was prepared. ICG+RSG has photothermal and photodynamic properties to eliminate bacteria at the infection site by releasing reactive oxygen species and increasing the temperature. Additionally, it regulates phagocytosis and macrophage polarization to modulate the immune response in the body. ICG+RSG kills bacteria and reduces tissue inflammation, showing potential for preventing implant infections.

A Double-Layer Hydrogel Dressing with High Mechanical Strength and Water Resistance Used for Drug Delivery.

Hydrogel dressings provide a moist wound healing environment, absorb the exudates of the wound, and have better biocompatibility than traditional dressings. However, it is still difficult to meet the needs of modern medicine due to the defects in drug burst release, weak mechanical strength, and poor water retention. To solve these problems, we developed a double-layer (DL) hydrogel based on ß-cyclodextrin polymer (ß-CDP), poly(vinyl alcohol) (PVA), and carboxymethyl cellulose sodium (CMC) via a layer-by-layer method. Inspired by natural coconut, this hydrogel consisted of a drug release layer (DRL) and a mechanical support layer (MSL). In our design, the introduction of ß-CDP into the DRL slowed the drug release rate of the DL hydrogel. Furthermore, the mechanical strength of the hydrogel was improved by immersing the MSL in a calcium chloride/boric acid solution. Combining these two layers, the tensile strength and elongation at break of the DL hydrogel reached 1504 kPa and 400%, respectively. More interestingly, the release mechanism of DL hydrogel conformed to the diffusion-relaxation-erosion model, which was different from traditional hydrogel dressings. Therefore, the as-prepared DL structure represents a feasible solution for fabricating high-performance mechanical hydrogel dressings with sustained drug release properties, and the DL hydrogel has potential to be used for medical dressings applied in daily life.

Dual-responsive nano-prodrug micelles for MRI-guided tumor PDT and immune synergistic therapy.

Micelles as nanocarriers not only offer new opportunities for early diagnosis and treatment of malignant cancers but also encounter numerous barriers in the path of efficient delivery of drugs to diseased areas in the body. To address these issues, we developed a pH/GSH responsive nano-prodrug micelle (NLG919/PGA-Cys-PPA@Gd) with a high drug-loading ratio and controlled drug release performance for MRI-guided tumor photodynamic therapy (PDT) and immune synergistic therapy. Under normal conditions, theranostic nanomicelles remained stable and in a photo-quenched state. Upon accumulation in the tumor site, however, the micelles demonstrated tumor microenvironment (TME) triggered photoactive formed-PPA (a photosensitizer) and NLG919 (an indoleamine 2,3-dioxygenase (IDO) inhibitor) release because the amide bonds of PGA-Cys-PPA and the disulfide linkage of Cys were sensitive to pH and GSH, respectively. More importantly, these micelles could avoid the undesired PPA leakage in blood circulation due to the conjugation between PPA and polymers. Furthermore, the obtained micelles could also enhance the contrast of T1-weighted MRI of tumors by virtue of their high relaxivity (r1 = 29.85 mM-1 s-1). In vitro and in vivo results illustrated that the micelles had good biocompatibility and biosafety. On the basis of the efficient drug delivery strategies in PDT and IDO pathway inhibition, this intelligent dual-drug delivery system could serve as an effective approach for MRI guided combination therapy of cancer.