Spatial Distributions of Guest Molecule and Hydration Level in Dendrimer-Based Guest-Host Complex.

Using the electrostatic complex of G4 poly(amidoamine) (PAMAM) dendrimer with an amphiphilic surfactant as a model system, contrast variation small angle neutron scattering (SANS) is implemented to resolve the key structural characteristics of dendrimer-based guest-host system. Quantifications of the radial distributions of the scattering length density and the hydration level within the complex molecule reveal that the surfactant is embedded in the peripheral region of dendrimer and the steric crowding in this region increases the backfolding of the dendritic segments, thereby reducing the hydration level throughout the complex molecule. The insights into the spatial location of the guest molecules as well as the perturbations of dendrimer conformation and hydration level deduced here are crucial for the delicate design of dendrimer-based guest-host system for biomedical applications.

Remotely triggered release of small molecules from LaB6@SiO2-loaded polycaprolactone microneedles.

We established near-infrared (NIR)-light-triggered transdermal delivery systems by encapsulating NIR absorbers, silica-coated lanthanum hexaboride (LaB6@SiO2) nanostructures and the cargo molecule to be released in biodegradable polycaprolactone (PCL) microneedles. Acting as a local heat source when exposed to an NIR laser, these nanostructures cause a phase transition of the microneedles, thereby increasing the mobility of the polymer chains and triggering drug release from the microneedles. On IR thermal images, the light-triggered melting behavior of the LaB6@SiO2-loaded microneedles was observed. By adjusting the irradiation time and the laser on/off cycles, the amount of molecules released was controlled accurately. Drug release was switched on and off for at least three cycles, and a consistent dose was delivered in each cycle with high reproducibility. The designed microneedles were remotely triggered by laser irradiation for the controlled release of a chemotherapeutic drug, doxorubicin hydrochloride, in vivo. This system would enable dosages to be adjusted accurately to achieve a desired effect, feature a low off-state drug leakage to minimize basal effects and can increase the flexibility of pharmacotherapy performed to treat various medical conditions.

PEGylation site-dependent structural heterogeneity study of monoPEGylated human parathyroid hormone fragment hPTH(1-34).

The structures of C- and N-terminally monoPEGylated human parathyroid hormone fragment hPTH(1-34) as well as their unmodified counterparts, poly(ethylene glycol) (PEG) and hPTH(1-34), have been studied by small-angle neutron scattering (SANS). The scattering results show that free hPTH(1-34) in 100 mM phosphate buffer (pH 7.4) aggregates into clusters. After conjugation with PEG, the PEG-peptide conjugates self-assemble into a supramolecular core-shell structure with a cylindrical shape. The PEG chains form a shell around the hPTH(1-34) core to shield hPTH(1-34) from the solvent. The detailed structural information on the self-assembled structures is extracted from SANS using a model of the cylindrical core with a shell of Gaussian chains attached to the core surface. On the basis of the data, because of the charge-dipole interactions between the conjugated PEG chain and the peptide, the conjugated PEG chain forms a more collapsed conformation compared to free PEG. Moreover, the size of the self-assembled structures formed by the C-terminally monoPEGylated hPTH(1-34) is about 3 times larger than that of the N-terminally monoPEGylated hPTH(1-34). The different aggregation numbers of the self-assembled structures, triggered by different PEGylation sites, are reported. These size discrepancies because of different PEGylation sites could potentially affect the pharmacokinetics of the hPTH(1-34) drug.