Complex hydrogels formed with chitosan (CS) and ring-opened polyvinyl pyrrolidone (roPVP) as a swellable mucoadhesive gastroretentive drug dosage form (smGRDDF) were prepared and characterized. CS/roPVP hydrogels were produced by blending CS with roPVP obtained by basic treatment of PVP. Effects of the heating time and NaOH concentration employed for preparing roPVP, and CS molecular weights (Mws), and roPVP/CS ratios on the swelling ability of the resultant hydrogels were characterized. Rheological characteristics were further examined. Results demonstrated that roPVP obtained in a 0.5 M NaOH solution heated to 50 °C for 4 h was suitable for producing complex hydrogels with CS. At a roPVP/CS ratio of 20:1, hydrogels composed of three different Mws of CS possessed optimal swelling and mucoadhesive abilities and rheological properties. In vitro dissolution revealed sustained drug release. A pharmacokinetic study exhibited that the plasma profile of alendronate followed a sustained manner with 3-fold enhancement of the oral bioavailability. In conclusion, the smGRDDF composed of CS/roPVP complex hydrogels was successfully developed and is potentially applicable to improve the clinical efficacy of bisphosphonates.

The potential clinical application of gadolinium-neutron capture therapy (Gd-NCT) for glioblastoma multiforme (GBM) treatment has been compromised by the fast clearance and nonspecific biodistribution of gadolinium-based agents. We have developed a stem cell–nanoparticle system (SNS) to actively target GBM for advanced Gd-NCT by magnetizing umbilical cord mesenchymal stem cells (UMSCs) using gadodiamide-concealed magnetic nanoparticles (Gd-FPFNP). Nanoformulated gadodiamide shielded by a dense surface composed of fucoidan and polyvinyl alcohol demonstrates enhanced cellular association and biocompatibility in UMSCs. The SNS preserves the ability of UMSCs to actively penetrate the blood brain barrier and home to GBM and, when magnetically navigates by an external magnetic field, an 8-fold increase in tumor-to-blood ratio is achieved compared with clinical data. In an orthotopic GBM-bearing rat model, using a single dose of irradiation and an ultra-low gadolinium dose (200 μg kg−1), SNS significantly attenuates GBM progression without inducing safety issues, prolonging median survival 2.5-fold compared to free gadodiamide. The SNS is a cell-based delivery system that integrates the strengths of cell therapy and nanotechnology, which provides an alternative strategy for the treatment of brain diseases.

In this study, lecithin-stabilized polymeric micelles (LsbPMs) were prepared to load quercetin (QUE) in order to improve its bioavailability and increase its antitumor activity. Its combination with doxorubicin (DOX) to minimize DOX-mediated cardiac toxicity and increase the antitumor activity of QUE-loaded LsbPMs was also examined. LsbPMs were prepared following a previously reported procedure. Results demonstrated that optimal QUE-loaded LsbPMs contained quercetin, D-α-tocopheryl polyethylene glycol succinate, and lecithin at a weight ratio of 6:40:80. Drug-release studies showed that QUE released from LsbPMs followed a controlled release pattern. A cytotoxicity assay revealed that QUE-loaded LsbPMs had significant anticancer activities against MCF-7, SKBR-3, and MDA-MB-231 human breast cancer cells and CT26 mouse colon cancer cells. In animal studies, intravenous administration of QUE-loaded LsbPMs resulted in efficient growth inhibition of CT26 colon cancer cells in a Balb/c mice model. In a pharmacokinetics study compared to free QUE, intravenous and oral administration of QUE-loaded LsbPMs was found to have significantly increased the relative bioavailability to 158% and 360%, respectively, and the absolute bioavailability to 5.13%. The effect of QUE-loaded LsbPMs in combination with DOX resulted in efficient growth inhibition of CT26 colon cancer cells and reduced cardiac toxicity in the Balb/c mice model.

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