Mesoporous silica coated spicules for photodynamic therapy of metastatic melanoma.

We report on the fabrication of mesoporous silicon dioxide coated Haliclona sp. spicules (mSHS) to enhance the delivery of the insoluble photosensitizer protoporphyrin IX (PpIX) into deep skin layers and mediate photodynamic therapy for metastatic melanoma in mice. The mSHS are dispersed sharp edged and rod-like micro-particles with a length of approximate 143.6 ± 6.4 µm and a specific surface area of 14.9 ± 3.4 m2/g. The mSHS can be topically applied to the skin, adapting to any desired skin area and lesion site. The insoluble PpIX were incorporated into the mesoporous silica coating layers of mSHS (mSHS@PpIX) with the maximum PpIX loading capacity of 120.3 ± 3.8 µg/mg. The mSHS@PpIX significantly enhanced the deposition of PpIX in the viable epidermis (5.1 ± 0.4 µg/cm2) and in the dermis (0.5 ± 0.2 µg/cm2), which was 154 ± 11-fold and 22 ± tenfold higher than those achieved by SHS, respectively. Topical delivery of PpIX using mSHS (mSHS@PpIX) completely eradicated the primary melanoma in mice in 10 days without recurrence or metastasis over 60 days. These results demonstrate that mSHS can be a promising topical drug delivery platform for the treatment of diverse cutaneous diseases, such as metastatic melanoma.

Experimental Study on the Roundness of Deep Holes in 7075 Aluminum Alloy Parts by Two-Dimensional Ultrasonic Elliptical Vibration Boring.

The 7075 aluminum alloy deep hole pipe finds extensive applications in the aerospace industry due to its remarkable attributes, such as high strength, exceptional wear resistance, and favorable mechanical properties. However, traditional boring processes for 7075 aluminum alloy deep hole pipes tend to generate elevated cutting forces, potentially leading to deformation issues in these deep holes. In response to these challenges, this study introduces a novel approach involving the use of a two-dimensional ultrasonic elliptical vibration tool. This tool features a single excitation asymmetric structure and aims to enhance the deep hole machining process in 7075 aluminum alloy. The research methodology involved several key steps. First, theoretical analysis and simulation were performed to study the motion trajectory of the cutting edge of the tool. Second, practical experiments were conducted comparing two-dimensional ultrasonic elliptical vibration boring with conventional boring for 7075 aluminum alloy deep hole pipes. The results demonstrate that, in contrast to conventional boring, two-dimensional ultrasonic vibration boring could achieve a maximum reduction of 54.1% and an average reduction of 50.4% in the roundness value of the deep holes. The impact of machining parameters on deep hole roundness is assessed through experimental analysis, leading to the determination of optimal processing parameters. In summary, this experimental research has a certain reference significance for the application of 7075 aluminum alloy deep hole parts in the aerospace field.

Transdermal delivery of heparin using low-frequency sonophoresis in combination with sponge spicules for venous thrombosis treatment.

This study reports that the use of low-frequency sonophoresis (LFS) in combination with sponge Haliclona sp. spicules (SHS), referred to as cSoSp (combined Sonophoresis and Spicules), can enhance the transdermal drug delivery in a synergistic manner. The topical application of cSoSp in vitro significantly enhanced the skin absorption of Fluorescent-Dextrans (4000 Da, FD-4K), a model drug of low-molecular-weight heparin (LMWH). The utilization of cSoSp dramatically increased the transdermal flux of FD-4K (188.6 ± 93.7 ng cm-2 h-1) compared to LFS (5.8 ± 3.1 ng cm-2 h-1) and SHS (3.2 ± 1.2 ng cm-2 h-1) among others. The mechanism of action of cSoSp could be attributed to the synergism between plenty of long-lasting nano-channels created by SHS and the disorders of SC lipids made by shock waves of LFS, which improves the homogeneity of the cavitation effects. Furthermore, LMWH (3000 Da) was transdermally delivered by using cSoSp to treat both superficial venous thrombosis (SVT) and deep venous thrombosis (DVT) in the marginal ear vein of rabbits with a good therapeutic effect. Furthermore, skin irritation and toxicity studies using guinea pigs indicated that cSoSp was nonirritating without any morphological changes in the keratinocytes. cSoSp offers a promising strategy to enhance the transdermal delivery of hydrophilic macromolecules such as heparin.