Doxorubicin (DOX)-wrapped zinc oxide nanoclusters (ZnO NCs) were developed for the therapy of colorectal cancer. DOX was coated onto the agglomerates of ZnO nanoparticles using a facile coating process. DOX-ZnO NCs with a hydrodynamic size of 170 nm, narrow size distribution, and positive zeta potential were fabricated. The aggregated shape of developed DOX-ZnO NCs was observed by transmission electron microscopy (TEM) imaging. The result of Fourier-transform infrared (FT-IR) analysis suggested the interaction between DOX and ZnO in DOX-ZnO NCs. The existence of DOX in the outer surface of DOX-ZnO NCs was further identified by X-ray powder diffractometer (XRD) and X-ray photoelectron spectroscopy (XPS) analyses. Cellular uptake efficiency and antiproliferation efficacy of developed DOX-ZnO NCs were tested in Caco-2 (human colorectal adenocarcinoma) cells. The cellular accumulated amount of DOX-ZnO NCs was 3.19-fold higher than that of free DOX (p < 0.05). The DOX-ZnO NCs group also exhibited improved antiproliferation potentials, compared with the DOX and ZnO groups, in Caco-2 cells at 0.5 and 1 μg/mL DOX concentrations. All these findings imply that developed DOX-ZnO NCs can be efficient hybrid nanoformulations for the therapy of colorectal cancers.

Hyaluronidase (HAase) inhibitor-incorporated hyaluronic acid (HA) hydrogel cross-linked with 1,4-butanediol diglycidyl ether (BDDE) was designed to reduce the toxicity risk induced by BDDE and its biodegradation rate in subcutaneous tissue. The formulation composition of hydrogel and its preparation method were optimized to have a high swelling ratio and drug content. Quercetin (QCT) and quetiapine (QTP), as an HAase inhibitor and model drug, respectively, were incorporated into the cross-linked hydrogel using the antisolvent precipitation method for extending their release after subcutaneous injection. The cross-linked HA (cHA)-based hydrogels displayed appropriate viscoelasticity and injectability for subcutaneous injection. The incorporation of QCT (as an HAase inhibitor) in the cHA hydrogel formulation resulted in slower in vitro and in vivo degradation profiles compared to the hydrogel without QCT. Single dosing of optimized hydrogel injected via a subcutaneous route in rats did not induce any acute toxicities in the blood chemistry and histological staining studies. In the pharmacokinetic study of rats following subcutaneous injection, the cHA hydrogel with QCT exhibited a lower maximum QTP concentration and longer half-life and mean residence time values compared to the hydrogel without QCT. All of these results support the designed HAase inhibitor-incorporated cHA hydrogel being a biocompatible subcutaneous injection formulation for sustained drug delivery.

A cream formulation containing Artemisia capillaris (AC) extract (ACE) was developed for psoriasis therapy. Although ACE can be dissolved in organic solvents, its topical application is restricted because of toxicities. Therefore, a cream formulation was developed for the convenient and safe local application of ACE on skin lesions. The antipsoriatic properties of the ACE cream were evaluated using an imiquimod‐ (IMQ‐) induced psoriasis‐like mouse model. In psoriasis‐like mouse models, the cumulative score (redness, thickness, and scaling) of the IMQ + ACE cream group was significantly lower than those of the other groups on day 4 (p < 0.05). The results of the hematoxylin and eosin staining of skin tissues revealed that the epidermal thickness value of the IMQ + ACE cream group was significantly lower than those of the other experimental groups (p < 0.05). The expression level of intracellular adhesion molecule‐1 (ICAM‐1), which indicates the leukocyte infiltration into the skin and subsequent interactions with keratinocytes, was also lower in the IMQ + ACE cream group than in the IMQ group. These results indicate that ACE cream formulation could be used safely and conveniently for psoriasis treatment.

The development of metal salts-based nanocomposites is highly desired for the Fenton or Fenton-like reaction-based chemodynamic therapy of cancer. Manganese sulfate (MnSO₄)-dispersed nanoparticles (NPs) were fabricated with a hot-melt extrusion (HME) system for the chemodynamic therapy of colorectal cancer in this study. MnSO₄ was homogeneously distributed in polyethylene glycol (PEG) 6000 (as a hydrophilic polymer) with the aid of surfactants (Span 80 and Tween 80) by HME processing. Nano-size distribution was achieved after dispersing the pulverized extrudate of MnSO₄-based composite in the aqueous media. The distribution of MnSO₄ in HME extrudate and the interactions between MnSO₄ and pharmaceutical additives were elucidated by Fourier-transform infrared, X-ray diffractometry, X-ray photoelectron spectroscopy, and scanning electron microscopy analyses. Hydroxyl radical generation efficiency by the Fenton-like chemistry capability of Mn²⁺ ion was also confirmed by catalytic assays. By using the intrinsic H₂O₂ in cancer cells, MnSO₄ NPs provided an elevated cellular reactive oxygen species level, apoptosis induction capability, and antiproliferation efficiency. The designed HME-processed MnSO₄ formulation can be efficiently used for the chemodynamic therapy of colorectal cancer.

Nanofiber (NF) membrane systems that can provide cascade catalytic reaction and ferroptosis induction were developed for oral cancer therapy. Glucose oxidase (GOx) and aminoferrocene (AF) were introduced into the NF system for glucose deprivation/H₂O₂ generation and OH radical generation, respectively. GOx offers starvation therapy and AF (including iron) provides chemodynamic therapy/ferroptosis for combating oral cancer. GOx (water-soluble) and AF (poorly water-soluble) molecules were successfully entrapped in the NF membrane via an electrospinning process. GOx and AF were incorporated into the polyvinyl alcohol (PVA)-based NF, resulting in PVA/GOx/AF NF with fast disintegration and immediate drug-release properties. In oral squamous cell carcinoma (YD-9 cells), the PVA/GOx/AF NF group exhibited higher cytotoxicity, antiproliferation potential, cellular ROS level, apoptosis induction, lipid ROS level, and malondialdehyde level compared to the other NF groups. The electrospun PVA/GOx/AF NF can be directly applied to oral cancer without causing pain, offering starvation/chemodynamic therapy and ferroptosis induction.