Injectable click-crosslinked hydrogel containing resveratrol to improve the therapeutic effect in triple negative breast cancer.

Triple-negative breast cancer (TNBC) patients are considered intractable, as this disease has few effective treatments and a very poor prognosis even in its early stages. Here, intratumoral therapy with resveratrol (Res), which has anticancer and metastasis inhibitory effects, was proposed for the effective treatment of TNBC. An injectable Res-loaded click-crosslinked hyaluronic acid (Res-Cx-HA) hydrogel was designed and intratumorally injected to generate a Res-Cx-HA depot inside the tumor. The Res-Cx-HA formulation exhibited good injectability into the tumor tissue, quick depot formation inside the tumor, and the depot remained inside the injected tumor for extended periods. In vivo formed Res-Cx-HA depots sustained Res inside the tumor for extended periods. More importantly, the bioavailability and therapeutic efficacy of Res remained almost exclusively within the tumor and not in other organs. Intratumoral injection of Res-Cx-HA in animal models resulted in significant negative tumor growth rates (i.e., the tumor volume decreased over time) coupled with large apoptotic cells and limited angiogenesis in tumors. Therefore, Res-Cx-HA intratumoral injection is a promising way to treat TNBC patients with high efficacy and minimal adverse effects.

Advances in Injectable In Situ-Forming Hydrogels for Intratumoral Treatment.

Chemotherapy has been linked to a variety of severe side effects, and the bioavailability of current chemotherapeutic agents is generally low, which decreases their effectiveness. Therefore, there is an ongoing effort to develop drug delivery systems to increase the bioavailability of these agents and minimize their side effects. Among these, intratumoral injections using in situ-forming hydrogels can improve drugs' bioavailability and minimize drugs' accumulation in non-target organs or tissues. This review describes different types of injectable in situ-forming hydrogels and their intratumoral injection for cancer treatment, after which we discuss the antitumor effects of intratumoral injection of drug-loaded hydrogels. This review concludes with perspectives on the future applicability of, and challenges for, the adoption of this drug delivery technology.

Preparation of Electrospun Small Intestinal Submucosa/Poly(caprolactone-co-Lactide-co-glycolide) Nanofiber Sheet as a Potential Drug Carrier.

In this work, we chose small intestine submucosa (SIS) as a drug carrier because SIS possesses good biocompatibility, non-immunogenic property and bio-resorbability, and performed electrospinning for preparation of nanofiber sheets (NS). For the preparation of drug-loaded electrospun SIS nanofiber sheets as a drug carrier, we used poly(ε-caprolactone-ran-l-lactide) (PCLA) copolymers to improve the electrospinning performance of SIS. The electrospinning of SIS and PCLA provided the electrospun SIS/PCLA (S/P)-nanofiber sheet (S/P-NS) with adjustable thickness and areas. The electrospun S/P-NS showed different porosities, pore sizes, diameters and tensile strengths depending on the ratios between SIS and PCLA. The electrospun S/P-NS was used as a drug carrier of the dexamethasone (Dex) and silver sulfadiazine (AgS) drug related to anti-inflammation. Dex-loaded S/P-NS and AgS-loaded S/P-NS was successfully fabricated by the electrospinning. In the in vitro and in vivo release, we successfully confirmed the possibility for the sustained release of Dex and AgS from the Dex-S/P-NS and AgS-S/P-NS for three weeks. In addition, the sustained Dex and AgS release suppressed the macrophage infiltration. Collectively, we achieved feasible development of SIS nanofiber sheets for a sustained Dex and AgS delivery system.

In Vivo Imaging of Click-Crosslinked Hydrogel Depots Following Intratympanic Injection.

In this study, we developed injectable intratympanic hyaluronic acid (HA) depots for the treatment of hearing loss. We prepared an injectable click-crosslinking formulation by modifying HA with tetrazine (HA-TET) and trans-cyclooctene (HA-TCO), which crosslinked to form an HA depot (Cx-HA). Preparation of the click-crosslinking HA formulation was facile, and Cx-HA depot formation was reproducible. Additionally, the Cx-HA hydrogel was significantly stiffer than HA hydrogel. To monitor the degradation pattern of hydrogels, we mixed a zwitterionic near-infrared (NIR) fluorophore (e.g., ZW800-1C) in the click-crosslinking HA formulation. Then, HA-TET and HA-TCO solutions containing ZW800-1C were loaded separately into the compartments of a dual-barrel syringe for intratympanic injection. The Cx-HA depots formed quickly, and an extended residence time in the tympanic cavity was confirmed by performing NIR fluorescence imaging. We have successfully prepared an injectable click-crosslinking HA formulation that has promise as an intratympanic drug depot.

Process specific differential metabolomes for industrial gochujang types (pepper paste) manufactured using white rice, brown rice, and wheat.

The metabolic perplexes for gochujang (GCJ) fermentative bioprocess, a traditional Korean pepper paste, has largely remain equivocal for preparative conditions and raw material (RM) additives exacerbating its commercial standardization. Herein, we outlined a differential non-targeted metabolite profiling for three GCJ (white rice-WR; brown rice-BR; wheat-WT) under varying processing steps (P1 - fermentation; P2 - meju addition; P3 - ripening; and P4 - red pepper addition). We correlated the process specific metabolomes with corresponding physicochemical factors, enzymatic phenotypes, and bioactivities for GCJ-types. The P1 was characterized by a uniform increase in the levels of RM-derived lysoPCs. In contrast, P2 was observed with proportionally higher levels of meju-released isoflavones and soyasaponins in WR-GCJ, followed by BR and WT-GCJ. The P3 involved a cumulative increase in primary metabolites in all GCJ samples except lower organic acid contents in WT-GCJ. The pepper derived flavonoids and alkaloids were selectively increased while P4 in all GCJ-types.

Metabolomics reveal that amino acids are the main contributors to antioxidant activity in wheat and rice gochujangs (Korean fermented red pepper paste).

Metabolite profiling of gochujangs (Korean fermented red pepper paste) produced from different kinds of raw materials (WG, wheat gochujang; RG, rice gochujang) was performed using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS). Using principal component analysis (PCA), gochujang samples were differentiated based on the differences in starchy source and secondary materials used in their production. The content of amino acids and sugars was higher in WG, whereas the content of flavonoids, soyasaponins, and γ-aminobutyric acid (GABA) was higher in RG. The content of flavonoids and soyasaponins was related to the higher soybean koji content of RG. The level of antioxidant activity in WG was higher than that in RG and showed a strong positive correlation with amino acid content and a negative correlation with flavonoid content. Although the Trolox equivalent antioxidant capacity of flavonoids was only 10-fold higher than that of amino acids in an antioxidant activity assay, the total amino acid content was as much as several hundred fold higher than total flavonoid content in gochujang. This result suggests that the amino acids could be a main contributor to the antioxidant capacity in gochujang.