Biocompatible and biodegradable water‐soluble dendrimers comprising ureas within the interior and amino groups on the periphery were synthesized in supercritical carbon dioxide (dendrimer of generation 1 shown in picture). This novel class of dendrimers shows a pH‐dependent intrinsic blue fluorescence at very low concentrations, which makes them potential polymeric fluorescent cell markers.

The design of small interfering RNA (siRNA) delivery materials showing efficacy in vivo is at the forefront of nanotherapeutics research. Polyurea (PURE-type) dendrimers are ‘smart’ biocompatible 3D polymers that unveil a dynamic and elegant back-folding mechanism involving hydrogen bonding between primary amines at the surface and tertiary amines and ureas at the core. Similarly, to a biological proton pump, they are able to automatically and reversibly transform their conformation in response to pH stimulus. Here, we show that PURE-G4 is a useful gene silencing platform showing no cellular toxicity. As a proof of concept we investigated the PURE-G4-siRNA dendriplex, which was shown to be an attractive platform with high transfection efficacy. The simplicity associated with the complexation of siRNA with polyurea dendrimers makes them a powerful tool for efficient cytosolic siRNA delivery.

Pulmonary administration offers excellent advantages over conventional drug delivery routes, including increasing therapeutics bioavailability, and avoiding long‐term safety issues. Formulations of nano‐in‐micro dry powders for lung delivery are engineered using (S)‐ibuprofen as a model drug. These biodegradable formulations comprise nanoparticles of drug‐loaded POxylated polyurea dendrimers coated with chitosan using supercritical‐fluid‐assisted spray drying. The formulations are characterized in terms of morphology, particle‐size distribution, in vitro aerodynamic particle pulmonary distribution, and glutathione‐S‐transferase assay. It is demonstrated that ibuprofen‐loaded nanoparticles can be successfully incorporated into microspheres with adequate aerodynamic properties, mass median aerodynamic diameter (1.86–3.83 μm), and fine particle fraction (28%–45%), for deposition into the deep lung. The (S)‐ibuprofen dry powder formulations show enhanced solubility, high swelling behavior and a sustained drug release at physiologic pH. Also, POxylated polyureas decrease the (S)‐ibuprofen toxic effect on cancer cellular growth. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS) assays show no significant cytotoxicity on the metabolic activity of human lung adenocarcinoma ephithelial (A549) cell line for the lowest concentration (1 × 10−3 m), even for longer periods of contact with the cells (up to 120 h), and in the normal human dermal fibroblasts cell line the toxic effect is also reduced.

The design of small interfering RNA (siRNA) delivery materials showing efficacy in vivo is at the forefront of nanotherapeutics research. Polyurea (PURE-type) dendrimers are 'smart' biocompatible 3D polymers that unveil a dynamic and elegant back-folding mechanism involving hydrogen bonding between primary amines at the surface and tertiary amines and ureas at the core. Similarly, to a biological proton pump, they are able to automatically and reversibly transform their conformation in response to pH stimulus. Here, we show that PURE-G4 is a useful gene silencing platform showing no cellular toxicity. As a proof of concept we investigated the PURE-G4-siRNA dendriplex, which was shown to be an attractive platform with high transfection efficacy. The simplicity associated with the complexation of siRNA with polyurea dendrimers makes them a powerful tool for efficient cytosolic siRNA delivery.

POxylated polyurea dendrimer (PUREG4OOx48)-based nanoparticles were loaded with paclitaxel (PTX) and doxorubicin (DOX) and micronized with chitosan (CHT) by using supercritical CO2-assisted spray drying (SASD). Respirable, biocompatible, and biodegradable dry powder formulations (DPFs) were produced to effectively transport and deliver the chemotherapeutics with a controlled rate to the deep lung. In vitro studies performed with the use of the lung adenocarcinoma cell line showed that DOX@PUREG4OOx48 nanoparticles were much more cytotoxic than the free drug. Additionally, the DPFs did not show higher cytotoxicity than the respective nanoparticles, and DOX-DPFs showed a higher chemotherapeutic effect than PTX formulations in adenocarcinoma cells.

Chitosan, a natural and abundant biopolymer has been long explored as a biocompatible material for the preparation of drug delivery devices. This strategy has been mostly accomplished using chemically crosslinked chitosan leading to more stable scaffolds. However, crosslinking has been shown to reduce both biocompatibility and swelling. In this work chitosan was crosslinked with novel biocompatible crosslinkers, based on oligo-oxazolines and glycidyl methacrylate copolymers, leading to patches with a very high swelling capacity. Dexamethasone therapeutics is strongly enhanced by a controlled release administration. This study shows that oligo-oxazoline-crosslinked chitosan is a suitable biomaterial for loading and controlled release of dexamethasone.

Chitosan, a natural and abundant biopolymer has been long explored as a biocompatible material for the preparation of drug delivery devices. This strategy has been mostly accomplished using chemically crosslinked chitosan leading to more stable scaffolds. However, crosslinking has been shown to reduce both biocompatibility and swelling. In this work chitosan was crosslinked with novel biocompatible crosslinkers, based on oligo-oxazolines and glycidyl methacrylate copolymers, leading to patches with a very high swelling capacity. Dexamethasone therapeutics is strongly enhanced by a controlled release administration. This study shows that oligo-oxazoline-crosslinked chitosan is a suitable biomaterial for loading and controlled release of dexamethasone.