Design and assembly of a nanoparticle, antibody, phthalocyanine scaffold for intracellular delivery of photosensitizer to human papillomavirus-transformed cancer cells.

In photodynamic therapy (PDT), internalization and uptake of the photosensitizer (PS) by the cells is a passive process that relies on the enhanced permeability and retention (EPR) effect of tumour tissues due to their vasculature, increased LDL receptors, and decreased lymphatic drainage in vivo. But as worries about PDT resistance grow, using passive techniques to administer PSs is becoming less and less viable. According to reported resistance mechanisms, it is necessary to improve PS delivery by changing PS absorption and bioavailability in order to enhance the therapeutic outcome. Therefore, in this study, a multifunctional photosensitizing agent with specific monoclonal antibodies (mAbs) to E6 oncoproteins was developed for PDT of human papillomavirus (HPV)-transformed cancer cells. Using PEGylated Gold Nanoparticles (PEGy-AuNP) at the core, anti-E6 mAbs and phthalocyanines were bound together. This compound demonstrated enhanced internalization of PS, resulting in enhanced PDT effects. In spite of being demonstrated in vitro, the substance in this work is intended for in vivo application, and conclusions are drawn to suggest possible outcomes for in vivo models based on observed data. By making PSs more bioavailable, facilitating their entry into cells, and preventing efflux through intracellular binding, this strategy may reduce cellular resistance to PDT.

[Intestinal absorption and metabolism of Puerariae Lobatae Radix decoction by in situ closed-loop method].

Biopharmaceutics classification system of Chinese materia medica (CMMBCS) emphasizes characteristic of the multi-component environment based on the drug solubility and permeability. In this study, the in situ closed-loop method combined with LC-MS technique was utilized to study the intestinal absorption and metabolism of Puerariae Lobatae Radix decoction (PLRD), providing selection basis for intestinal permeability components in CMMBCS. A total of 36 components were identified from PLRD. Among them, 17 components could be detected in the plasma sample, indicating that 17 components could be absorbed into blood, so these 17 components could be used as intestinal permeability evaluation components in CMMBCS. The other 19 components were not detected in the plasma sample, suggesting that they may not be absorbed or metabolized by the gut wall enzymes.

Intestinal absorption and metabolism of Puerariae Lobatae Radix decoction by in situ closed-loop method / 中国中药杂志

Biopharmaceutics classification system of Chinese materia medica (CMMBCS) emphasizes characteristic of the multi-component environment based on the drug solubility and permeability. In this study, the in situ closed-loop method combined with LC-MS technique was utilized to study the intestinal absorption and metabolism of Puerariae Lobatae Radix decoction (PLRD), providing selection basis for intestinal permeability components in CMMBCS. A total of 36 components were identified from PLRD. Among them, 17 components could be detected in the plasma sample, indicating that 17 components could be absorbed into blood, so these 17 components could be used as intestinal permeability evaluation components in CMMBCS. The other 19 components were not detected in the plasma sample, suggesting that they may not be absorbed or metabolized by the gut wall enzymes.

[Absorption and metabolism of Chuanxiong Rhizoma decoction with multi-component sequential metabolism method].

The multiple components in Chinese herbal medicines (CHMS) will experience complex absorption and metabolism before entering the blood system. Previous studies often lay emphasis on the components in blood. However, the dynamic and sequential absorption and metabolism process following multi-component oral administration has not been studied. In this study, the in situ closed-loop method combined with LC-MS techniques were employed to study the sequential process of Chuanxiong Rhizoma decoction (RCD). A total of 14 major components were identified in RCD. Among them, ferulic acid, senkyunolide J, senkyunolide I, senkyunolide F, senkyunolide G, and butylidenephthalide were detected in all of the samples, indicating that the six components could be absorbed into blood in prototype. Butylphthalide, E-ligustilide, Z-ligustilide, cnidilide, senkyunolide A and senkyunolide Q were not detected in all the samples, suggesting that the six components may not be absorbed or metabolized before entering the hepatic portal vein. Senkyunolide H could be metabolized by the liver, while senkyunolide M could be metabolized by both liver and intestinal flora. This study clearly demonstrated the changes in the absorption and metabolism process following multi-component oral administration of RCD, so as to convert the static multi-component absorption process into a comprehensive dynamic and continuous absorption and metabolism process.

Absorption and metabolism of Chuanxiong Rhizoma decoction with multi-component sequential metabolism method / 中国中药杂志

The multiple components in Chinese herbal medicines (CHMS) will experience complex absorption and metabolism before entering the blood system. Previous studies often lay emphasis on the components in blood. However, the dynamic and sequential absorption and metabolism process following multi-component oral administration has not been studied. In this study, the in situ closed-loop method combined with LC-MS techniques were employed to study the sequential process of Chuanxiong Rhizoma decoction (RCD). A total of 14 major components were identified in RCD. Among them, ferulic acid, senkyunolide J, senkyunolide I, senkyunolide F, senkyunolide G, and butylidenephthalide were detected in all of the samples, indicating that the six components could be absorbed into blood in prototype. Butylphthalide, E-ligustilide, Z-ligustilide, cnidilide, senkyunolide A and senkyunolide Q were not detected in all the samples, suggesting that the six components may not be absorbed or metabolized before entering the hepatic portal vein. Senkyunolide H could be metabolized by the liver, while senkyunolide M could be metabolized by both liver and intestinal flora. This study clearly demonstrated the changes in the absorption and metabolism process following multi-component oral administration of RCD, so as to convert the static multi-component absorption process into a comprehensive dynamic and continuous absorption and metabolism process.

Application analysis on theory of “correlation in quality, curative effect, and metabolism” in quality control of genuine medicinal materials / 中草药

Genuine medicinal materials (GMM) is the representative of high quality materials, the particular area, excellent quality, and good efficacy make it into the essence of traditional Chinese medicine (TCM). But the scientific connotation of the GMM quality and the relationship between the quality and efficacy of GMM are the emphases and difficulty in its study. The evaluation on the theory system of “correlation in quality, curative effect, and metabolism” is carried on the curative effect with GMMs and non-GMMs as research objects and the simultaneous detection of multi-components as means. The “correlation in quality, efficacy, and metabolism” is based on the combination of chemical analysis method, pharmacological model experiment, and mathematical analysis model calculation method. The quality evaluation indexes and methods of GMM are disscused and the quality of GMM is assessed by the various views of absorption, metabolism, and effectiveness of TCM. At first, the fingerprint method to identify and select the quality control components of GMM is adopted and the qualitative and quantitative methods of multi-components in GMM are established in this study. Then the “correlation of quality, curative effect, and metabolism” is experimented through the comparison on physiological animals and model animals, the constituents are comprehensively investigated. Finally, based on the mathematical models for the medicines-related methods, we can get the components with preferred quality control, which associates with the efficacy and the proportional relationship, ascertain the material basis for the efficacy of GMM, establish a scientific optimal quality evaluation system, and provide the new ideas for the research of GMM.