It has recently emerged that drugs such as the mTOR inhibitor rapamycin (Rapa) may play a key role in the treatment of airway inflammation associated with lung diseases, such as chronic obstructive pulmonary disease, asthma, and cystic fibrosis. Nevertheless, Rapa clinical application is still prevented by its unfavorable chemical-physical properties, limited oral bioavailability, and adverse effects related to non-specific biodistribution. In this paper, the design and production of a novel formulation of Rapa based on nano into micro (NiM) particles are detailed. To achieve it, Rapa-loaded nanoparticles were produced by nanoprecipitation of an amphiphilic pegylated poly-ɛ-caprolactone/polyhydroxyethyl aspartamide graft copolymer. The obtained nanoparticles that showed a drug loading of 14.4 wt% (corresponding to an encapsulation efficiency of 82 wt%) did not interact with mucins and were able to release and protect Rapa from degradation in simulated lung and cell fluids. To allow their local administration to the lungs as a dry powder, particle engineering at micro-sized level was done by embedding nanoparticles into mannitol-based microparticles by spray drying. Obtained NiM particles had a mean diameter of about 2-µ, spherical shape and had good potential to be delivered to the lungs by a breath-activated dry powder inhalers. Rheological and turbidity experiments showed that these NiM particles can dissolve in lung simulated fluid and deliver the Rapa-loaded pegylated nanoparticles, which can diffuse through the mucus layer. Graphical abstract

Very recently, significant attention has been focused on the adsorption and cell adhesion properties of graphene oxide (GO), because it is expected to allow high drug loading and controlled drug release, as well as the promotion of cell adhesion and proliferation. This is particularly interesting in the promotion of wound healing, where antibiotics and anti-inflammatories should be locally released for a prolonged time to allow fibroblast proliferation. Here, we designed an implantable patch consisting of poly(caprolactone) electrospun covered with GO, henceforth named GO–PCL, endowed with high ibuprofen (5.85 mg cm⁻²), ketoprofen (0.86 mg cm⁻²), and vancomycin (0.95 mg cm⁻²) loading, used as anti-inflammatory and antibiotic models respectively, and capable of responding to near infrared (NIR)-light stimuli in order to promptly release the payload on-demand beyond three days. Furthermore, we demonstrated the GO is able to promote fibroblast adhesion, a key characteristic to potentially provide wound healing in vivo.

Theranostic systems have attracted considerable attention for their multifunctional approach to cancer. Among these, carbon nanodots (CDs) emerged as luminescent nanomaterials due to their exceptional chemical properties, synthetic ease, biocompatibility, and for their photothermal and fluorescent properties useful in cancer photothermal therapy. However, premature renal excretion due to the small size of these particles limits their biomedical application. To overcome these limitations, here, hybrid poly(lactic-co-glycolic acid) (PLGA-CDs) nanoparticles with suitable size distribution and stability have been developed. CDs were decisive in the preparation of polymeric nanoparticles, not only conferring them photothermal and fluorescent properties, needed in theranostics, but also having a strategic role in the stabilization of the system in aqueous media. In fact, CDs provide stable PLGA-based nanoparticles in aqueous media and sufficient cryoprotection in combination with 1% PVP. While PLGA nanoparticles required at least 5% of sucrose. Comparing nanosystems with different CDs content, it is also evident how these positively impinge on the loading and release of the drug, favoring high drug loading (~4.5%) and a sustained drug release over 48 h. The therapeutic and imaging potentials were finally confirmed through in vitro studies on a breast cancer cell line (MDA-MB-231) using fluorescence imaging and the MTS cell viability assay.