Stabilization and Movable Ligand-Modification by Folate-Appended Polyrotaxanes for Systemic Delivery of siRNA Polyplex.

To achieve a systemic targeted delivery of siRNA using polymeric carriers, there is a dilemma between ligand modification and stabilization of the polyplex. Namely, ligand modification often leads to destabilization of the polyplex in the blood circulation. In fact, we previously developed cyclodextrin (CD)/polyamidoamine dendrimer conjugates (CDE) as siRNA carriers, and the interaction of CDE/siRNA was decreased by the conjugation with folate-polyethylene glycol, leading to the destabilization. To overcome this dilemma, in this study, folate-appended polyrotaxanes (Fol-PRX) were developed. Fol-PRX stabilized CDE/siRNA polyplex by intermolecularly connecting CDE molecules through a host-guest interaction between adamantane at the terminals of Fol-PRX and ß-CD in the polyplex. Moreover, the intermolecular connection of the polyplex with Fol-PRX provided movable folate moieties on the surface. As a result, Fol-PRXs enhanced the in vivo antitumor activity of the polyplex after intravenous administration, suggesting their utility as the dual-functional materials for systemic delivery of siRNA polyplexes.

Development and Characterization of Furfuryl-Gelatin Electrospun Scaffolds for Cardiac Tissue Engineering.

In this study, three types of electrospun scaffolds, including furfuryl-gelatin (f-gelatin) alone, f-gelatin with polycaprolactone (PCL) in a 1:1 ratio, and coaxial scaffolds with PCL (core) and f-gelatin (sheath), were developed for tissue engineering applications. Scaffolds were developed through single nozzle electrospinning and coaxial electrospinning, respectively, to serve as scaffolds for cardiac tissue engineering. Uniform fibrous structures were revealed in the scaffolds with significantly varying average fiber diameters of 760 ± 80 nm (f-gelatin), 420 ± 110 nm [f-gelatin and PCL (1:1)], and 810 ± 60 nm (coaxial f-gelatin > PCL) via scanning electron microscopy. The distinction between the core and the sheath of the fibers of the coaxial f-gelatin > PCL electrospun fibrous scaffolds was revealed by transmission electron microscopy. Thermal analysis and Fourier transformed infrared (FTIR) spectroscopy revealed no interactions between the polymers in the blended electrospun scaffolds. The varied blending methods led to significant differences in the elastic moduli of the electrospun scaffolds with the coaxial f-gelatin > PCL revealing the highest elastic modulus of all scaffolds (164 ± 3.85 kPa). All scaffolds exhibited excellent biocompatibility by supporting the adhesion and proliferation of human AC16 cardiomyocytes cells. The biocompatibility of the coaxial f-gelatin > PCL scaffolds with superior elastic modulus was assessed further through adhesion and functionality of human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes, thereby demonstrating the potential of the coaxially spun scaffolds as an ideal platform for developing cardiac tissue-on-a-chip models. Our results demonstrate a facile approach to produce visible light cross-linkable, hybrid, biodegradable nanofibrous scaffold biomaterials, which can serve as platforms for cardiac tissue engineered models.

Synthesis and Characterization of Polyethylene Glycol-Grafted Photoreactive Polyethylene Glycols for Antibiofouling Applications.

Notably, antibiofouling is an important and predominant technique adopted to improve the surfaces of biomaterials. In this study, polyethylene glycol-grafted polyethylene glycols bearing azidophenyl groups were synthesized and immobilized on polystyrene surfaces via photoirradiation. The prepared polymers were found to be highly soluble in water, and photoimmobilization with fluorescent proteins was confirmed based on micropatterning using a photomask. These polymers suppressed nonspecific interactions between proteins and cells on the substrate. Considering that photoimmobilization can be adopted for the covalent bond modification of various surfaces, the developed water-soluble and highly antibiofouling polymers appear to be useful in biomaterial preparation.

Colon-specific tablets containing 5-fluorouracil microsponges for colon cancer targeting.

Most anticancer medications undergo major first-pass metabolism in the intestinal wall, the liver, or both. 5-fluorouracil (5-FU) is known to have erratic oral bioavailability due to first-pass metabolism. The present study aimed to develop 5-FU-loaded microsponges (MS) compressed in enteric-coated tablets as a new colon targeting to colorectal cancer. MS was prepared as a controlled release system for 5-FU and characterized for drug encapsulation efficiency, and surface morphology. Further, hydroxypropyl methylcellulose (HPMC) was mixed with pectin and characterized for their flow as a tablet coat enclosing the core tablets of 5-FU-MS. Moreover, in vitro drug release behavior was studied in different pH media, while the X-ray imaging was used to monitor the in vivo movement of prepared tablets containing 5-FU-MS throughout the GI system. The results showed that MS were spherical in shape and have several pores on their surfaces. The encapsulation efficiency was from 71.80 ± 1.62% - 101.3 ± 2.60%, while the particle size was from 53.11 ± 41.03 - 118.12 ± 48.21 nm. The formulated tablets were fulfilling all official and other specifications and exhibited sustained release of 5-FU only inside the colon. The in vivo human volunteer study of X-ray has shown that the tablets ultimately reached the colon without disturbing in the upper GI system. The obtained carrier formulation is considered as a novel system to deliver 5-FU to the colon tumor with 100% targeting without any drug release in the upper GIT or first-pass metabolism.