1.Biodegradable, elastomeric coatings with controlled anti-proliferative agent release for magnesium-based cardiovascular stents.
Gu X1, Mao Z2, Ye SH1, Koo Y3, Yun Y3, Tiasha TR4, Shanov V4, Wagner WR5. Colloids Surf B Biointerfaces. 2016 Apr 7;144:170-179. doi: 10.1016/j.colsurfb.2016.03.086. [Epub ahead of print]
Vascular stent design continues to evolve to further improve the efficacy and minimize the risks associated with these devices. Drug-eluting coatings have been widely adopted and, more recently, biodegradable stents have been the focus of extensive evaluation. In this report, biodegradable elastomeric polyurethanes were synthesized and applied as drug-eluting coatings for a relatively new class of degradable vascular stents based on Mg. The dynamic degradation behavior, hemocompatibility and drug release were investigated for poly(carbonate urethane) urea (PCUU) and poly(ester urethane) urea (PEUU) coated magnesium alloy (AZ31) stents. Poly(lactic-co-glycolic acid) (PLGA) coated and bare stents were employed as control groups. The PCUU coating effectively slowed the Mg alloy corrosion in dynamic degradation testing compared to PEUU-coated, PLGA-coated and bare Mg alloy stents. This was confirmed by electron microscopy, energy-dispersive x-ray spectroscopy and magnesium ion release experiments.
2.Investigation on Drug Solubility Enhancement Using Deep Eutectic Solvents and Their Derivatives.
Li Z1, Lee PI2. Int J Pharm. 2016 Apr 11. pii: S0378-5173(16)30301-5. doi: 10.1016/j.ijpharm.2016.04.018. [Epub ahead of print]
Deep eutectic solvent (DES) is a room temperature liquid typically formed by mixing two solid compounds, such as a quaternary ammonium salt (QAS) (e.g. choline chloride) and a hydrogen bond donor (HBD) (e.g. urea or a carboxylic acid) at their eutectic composition. Very often, a range of room temperature liquids can also be obtained near the eutectic composition. Hence, it is more convenient to introduce a more general term deep eutectic solvent derivatives (DESDs) to describe a wide range of DES-like derivatives including those derived from ternary mixtures. The melting point of the mixture is lowered because the hydrogen bonding between DESD components reduces the lattice energy of components of the eutectic system. Based on the analysis of available data for 22 such choline chloride-based DES pairs, we found that the observed melting point depression can be statistically correlated with the difference between the hydrogen bonding contribution (δh) and the polar contribution (δp) to the solubility parameter of the hydrogen bond donor (HBD) component.
3.A tunable delivery platform to provide local chemotherapy for pancreatic ductal adenocarcinoma.
Indolfi L1, Ligorio M2, Ting DT3, Xega K4, Tzafriri AR5, Bersani F4, Aceto N4, Thapar V4, Fuchs BC4, Deshpande V4, Baker AB6, Ferrone CR4, Haber DA7, Langer R8, Clark JW4, Edelman ER9. Biomaterials. 2016 Mar 31;93:71-82. doi: 10.1016/j.biomaterials.2016.03.044. [Epub ahead of print]
Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating and painful cancers. It is often highly resistant to therapy owing to inherent chemoresistance and the desmoplastic response that creates a barrier of fibrous tissue preventing transport of chemotherapeutics into the tumor. The growth of the tumor in pancreatic cancer often leads to invasion of other organs and partial or complete biliary obstruction, inducing intense pain for patients and necessitating tumor resection or repeated stenting. Here, we have developed a delivery device to provide enhanced palliative therapy for pancreatic cancer patients by providing high concentrations of chemotherapeutic compounds locally at the tumor site. This treatment could reduce the need for repeated procedures in advanced PDAC patients to debulk the tumor mass or stent the obstructed bile duct. To facilitate clinical translation, we created the device out of currently approved materials and drugs.
4.Controlled Release of Chemotherapeutic Platinum-bisphosphonate Complexes from Injectable Calcium Phosphate Cements.
Farbod K1, Sariibrahimoglu K2, Curci A3, Hayrapetyan A4, Hakvoort JN5, van den Beucken J6, Iafisco M7, Margiotta N8, Leeuwenburgh SC9. Tissue Eng Part A. 2016 Apr 15. [Epub ahead of print]
Herein we present a method to release chemotherapeutic platinum-bisphosphonate (Pt-BP) complexes from apatitic calcium phosphate cements (CPCs). Pt-BP-loaded hydroxyapatite nanoparticles (HA NPs) were added at different ratios to the powder phase of the cements, which contained poly(D,L-lactic-co-glycolic) acid (PLGA) microspheres as porogens to accelerate their degradation. In vitro release kinetics of Pt-BP complexes revealed that the release rate of Pt-species can be tuned by varying the amount of drug-loaded HA NPs as well as modifying the chemical structure of the Pt-BP complex to tailor its affinity with HA NPs. In addition, the incorporation of PLGA microspheres into the CPCs increased the degradation rate of the materials without affecting the release rate of Pt-species. Finally, the anti-proliferative activity of the free Pt-BP complexes and Pt-BP-loaded CPCs was evaluated using both human osteosarcoma cancer cells (MG-63) and human bone marrow-derived mesenchymal stromal cells (h-BMMSCs).