Current Drug Metabolism - Volume 23, Issue 8, 2022

Despite the great efforts that have been achieved in breast cancer treatment, it remains a significant cause of death in women and is a serious health problem. Treatment with chemotherapy drugs faces various challenges, such as toxicity and chemoresistance to chemotherapeutic drugs, which hinder their therapeutic success and clinical experiments. This review focuses on targeting nanocarrier approaches to target chemotherapy drugs to receptor targets that are overexpressed on the surface of breast cancer cells. In particular, the most commonly targeted nanocarriers for the chemotherapeutic agents examined by the different researcher groups, such as liposomes, dendrimers, polymeric micelles, lipid particulates, polymeric nanoparticles, and carbon nanotubes, have been reviewed. Moreover, we summarized the molecular receptors or targets that are the most commonly overexpressed in breast cancer cells and the natural and synthetic ligands studied for use as targeting moieties to functionalize chemotherapeutically loaded nanocarriers for potential specific breast cancer targeting.

Cancer accounts for the high mortality rate and limits the life expectancy of an individual. As per the WHO report of 2020, cancer accounts for >10 million deaths globally. Scientists are continuously pitching toward the development of novel techniques to combat this menace and enhance the efficacy of prevailing molecules. In the early phases of the drug development process, >40% of promising new therapeutic molecules are hydrophobic. Low aqueous solubility results in compromised bioavailability on administration. This limitation is a major drawback for the therapeutic use of anticancer drugs. Drug nanocrystals (NCs) have sparked a lot of interest in drug delivery. This might be due to their excellent physicochemical characteristics like tailored dissolution, high drug loading efficiency, extended circulation period, and high structural stability. There are ‘n’ a number of the characteristics that make drug nanocrystals a promising formulation for the treatment of cancer. In the last few years, many hydrophobic or lipophilic drugs like camptothecin, paclitaxel, cyclosporin, busulfan, and thymectacin have been formulated as drug nanocrystals against anticancer therapeutics. Various formulation technologies have been developed in conjunction with nanocrystal development. This includes top-down approaches, bottom-up approaches, as well as combination technology. In this article, we will focus on the various manufacturing processes, biological fate and therapeutic applications of NCs, and future perspectives in the management of cancer.

The pharmaceutical industry is moving towards the future and is witnessing innovation in drug development through the introduction of personalized medicine technologies. Instead of adapting the dose thata patient needs, they were adapted to the manufacturer’s dose. Nowpatient-specific or customized dosing methods and dosing combinations have superior persistence to the standard mass-produced drugs. Printing technology has gained interest during the last few years to manufacture personalized dosage forms. For manufacturing personalized drug products, three-dimensional printing (3DP) has expanded to the pharmaceutical industry. With the approval of the first 3DP product, an unprecedented opportunity for discovering new compounds and technologies has arisen. This article has re-evaluated various printing technology and theirutilization in personalized medicines. Further, we also discussed its history, advantages, challenges and differenttypes of printing technologies with advantages and limitations, particularly in the area of pharmaceutical research.

Background: Vitamin D is a fat-soluble vitamin, and it is a potential key factor in maintaining a healthy status. Various observational studies have reported the association between vitamin D deficiency and an elevated risk of osteoporosis, cardiovascular disease, diabetes mellitus, and certain types of cancer. The number of studies that investigates the genetic determinants of vitamin D hydroxy metabolism has been growing. Still, its association with the genetic variants remains unclear, particularly those genes related to vitamin D metabolism. Aims: This work is a comprehensive review of available evidence of the effect of genetic variants on vitamin D metabolism and their impact on vitamin D status in the human body, disorders including coronavirus disease 2019 infection, and its importance for clinical investigators and public health. Results: Genome-wide association studies and candidate gene studies show that genetic factors are influencing the circulating levels of vitamin D. These genetic changes are implicated in various pathways of vitamin D, such as metabolism and transport. It is also involved in the formation of the ternary complex (vitamin D receptor - retinoid receptor - transcription factor II B). Conclusion: Linkage studies may fail to identify replicated genetic architecture of vitD metabolism. Genome-wide association studies and the candidate gene approach have shown reproducible influences of gene control on vitD status.

Aims: In this study, we aim to establish an integrated research strategy for the rapid chemical profiling of Compound Huanggen Granules (CHG) and absorbed prototypes in plasma by integrating the UHPLC-Q-TOF-MS^E method and data post-processing strategy, to provide some valuable research basis for the further studies on the quality control, pharmacokinetics and pharmacodynamics of CHG. Background: Compound Huanggen Granules (CHG), a traditional Chinese medicine (TCM) hospital preparation, has long been used in clinical practice for the prevention and treatment of liver fibrosis. However, due to the lack of in vitro chemical and in vivo metabolism studies, its pharmacodynamic material basis is still unrevealed. Objective: To simplify the mass data post-processing process and enhance the structural identification efficiency by reducing the possibility of false positive, and rapidly identify the absorbed prototypes in plasma after oral administration of CHG. Methods: An analytical strategy integrating ultra high-performance liquid chromatography coupled with quadrupletime- of-flight mass spectrometry (UHPLC-Q-TOF-MS^E, E represents collision energy) method and data postprocessing strategy based on a self-built in-house components database was established and utilized for the rapid characterization of the multi-constituents of CHG and prototypes in cynomolgus monkey plasma after oral administration. Results: As a result, a total of 81 compounds, including 14 phenolic acids, 6 coumarins, 25 flavonoids, 5 anthraquinones, 5 phenylpropanoids, 15 triterpenoid saponins, and 11 others, were plausibly or unambiguously identified based on their accurate masses, and MS/MS fragment pathways analysis, and also by comparison of retention time and MS data with reference standards. In the in vivo study, according to the extracted ion chromatograms (EICs) of identified components, 34 absorbed prototypical components were rapidly identified in cynomolgus monkey plasma after oral administration. Conclusion: It was demonstrated that the data post-processing strategy applied in this study could greatly simplify the data post-processing process and enhance the structural identification efficiency by reducing the possibility of false positives, and the results obtained might be helpful for further studies on the quality control, pharmacokinetics and pharmacodynamics of CHG.

Aims: This study aimed to investigate the effects of consuming Phoenix dactylifera and fasting on the mRNA expression of major hepatic drug-metabolizing enzymes in mice. Methods: Phoenix dactylifera ethanolic extract was analyzed using LC-MS/MS. We used forty-two male Balb/c mice, which were treated with low (300 mg/kg) and high (2583 mg/kg) doses of Phoenix dactylifera and fasted for 24 hours, two weeks, and one month. Then, we analyzed the expression of cyp3a11, cyp2c29, cyp2d9, and ugt2b1 using real-time polymerase chain reaction assay. In addition, we assessed the relative liver weights of the mice and the hepatic phathohistological alterations. Results: We found that Phoenix dactylifera ethanolic extract contained 38 phytochemical compounds, mainly kaempherol, campesterol, lutein, apigenin, genistein, and isoquercetin. Fasting significantly upregulated the mRNA expression of several drug-metabolizing enzymes in a time-dependent manner and we showed that consuming the low dose of Phoenix dactylifera significantly upregulated the expression of drug-metabolizing enzymes more than the high dose. The results of the histological examinations and relative liver weight showed that fasting and consuming of Phoenix dactylifera did not cause any toxicological alterations in the liver of the mice. Conclusion: It is concluded from this study that fasting and consuming of Phoenix dactylifera upregulated the mRNA expression of major drug-metabolizing enzymes in mouse livers. These findings may explain, at least partly, the variation of drug response during fasting in the month of Ramadan and would direct future clinical studies in optimizing the dosing of pharmacotherapeutic regimen.