Stereocomplexed PLA microspheres: Control over morphology, drug encapsulation and anticancer activity.

Lung cancer is the leading cause of cancer death because of smoking and air pollution. Therefore, new ideas should be provided for lung cancer treatment in which the delivery of anticancer drugs to the local tumor site can be achieved. For this purpose, we propose the use of stereocomplexed spherical microspheres with sizes between 0.5 and 10 µm loaded with doxorubicin (DOX) to be administered through the nasal route. In order to gain control over the microsphere morphology, size, and drug loading capacity, we systematically studied the influence of the solvent used for preparation and the functionalization of their building blocks, namely poly-l-lactide (PLLA) and poly-d-lactide (PDLA) with blocked or unblocked l-proline moieties. We could demonstrate that DOX release is generally determined by the size of the microspheres. The antiproliferative activity of DOX released from the different microspheres was shown in vitro using the A549 lung cancer cell line as a model. Moreover, when in direct contact to the cancer cells, smaller microspheres were uptaken and could serve as a reservoir for local drug release. Our findings not only provide a novel strategy to prepare PLA microspheres with controllable morphology and release of anti-cancer drugs but also offer additional possibilities for the application of stereocomplexed particles in anticancer therapy, with suitable sizes for nasal administration.

Rational design of dendritic thermoresponsive nanogels that undergo phase transition under endolysosomal conditions.

In the last few decades, the synthesis of nanodevices has become a very active research field with many applications in biochemistry, biotechnology, and biomedicine. However, there is still a great need for smart nanomaterials that can sense and respond to environmental changes. Temperature- and pH-responsive nanogels (NGs), which are prepared in a one-pot synthesis from N-isopropylacrylamide (NiPAm) and a Newkome-type dendron (ABC) bearing carboxylic acid groups, are being investigated as multi-responsive drug carriers. As a result, NGs have been developed that are able to undergo a reversible volume phase transition triggered by acidic conditions, like the ones found in endolysosomal compartments of cancer cells. The NGs have been thoroughly characterized using dynamic light scattering and spectroscopies, such as infrared, nuclear magnetic resonance, UV-visible, and stimulated Raman. Strong hydrogen bonds have been detected when the ABC moieties are deprotonated, which has led to changes in the transition temperatures of the NGs and a reversible, pH-dependent aggregation. This pH-dependent phase change was exploited for the effective encapsulation and sustained release of the anticancer drug cisplatin and resulted in a faster release of the drug at endolysosomal pH values. The cisplatin-loaded NGs have exhibited high toxicities against A549 cells in vitro, while the unloaded NGs have been found to be not cytotoxic and hemocompatible.

Immobilization of Stimuli-Responsive Nanogels onto Honeycomb Porous Surfaces and Controlled Release of Proteins.

In this article, we describe the formation of functional honeycomb-like porous surfaces fabricated by the breath figures technique using blends of either amino-terminated poly(styrene) or a poly(styrene)-b-poly(acrylic acid) block copolymer with homopoly(styrene). Thus, the porous interfaces exhibited either amino or acid groups selectively located inside of the holes, which were subsequently employed to anchor stimuli-responsive nanogels by electrostatic interactions. These nanogels were prepared from poly(N-isopropylacrylamide) (PNIPAM) cross-linked with dendritic polyglycerol (dPG) and semi-interpenetrated with either 2-(dimethylamino)ethyl methacrylate (DMAEMA) or 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) to produce positively and negatively charged nanogel surfaces, respectively. The immobilization of these semi-interpenetrated networks onto the surfaces allowed us to have unique stimuli-responsive surfaces with both controlled topography and composition. More interestingly, the surfaces exhibited stimuli-responsive behavior by variations on the pH or temperature. Finally, the surfaces were evaluated regarding their capacity to induce a thermally triggered protein release at temperatures above the cloud point temperature (T(cp)) of the nanogels.