ADMET and DMPK最新文献

Background and purpose: Physicochemical properties of an amorphous solid dispersion (ASD) comprising an experimental grade of hydroxypropyl methylcellulose acetate succinate (HPMCAS-MX) with lower glass transition temperature have been previously investigated. This study aimed to evaluate applicability of HPMCAS-MX to hot-melt extrusion (HME) and dissolution-permeation performance of prepared ASDs using MicroFLUX.

Review approach: A physical mixture of indomethacin (IMC) and HPMCAS-MX or -MG (a commercial grade with higher transition temperature) at 20:80 weight ratio was hot-melt extruded to prepare an ASD (IMC-MX and IMC-MG, respectively). The dissolution-permeation performance and the stability of the ASDs were measured.

Key results: A torque reduction at 120 °C implied that IMC-MX transformed into an amorphous state at this temperature, but IMC-MG required around 170 °C. This result was supported by Raman mapping of the the HME samples. IMC-MG and IMC-MX remained in an amorphous state at 40 °C for three months. The initial dissolution rate and solubility of the ASDs were higher than that of crystalline IMC. The apparent permeability of IMC from IMC-MX and IMC-MG was comparable but was approximately two-fold higher than that from crystalline IMC.

Conclusion: HPMCAS-MX enabled HME process at a lower temperature and improved the dissolution-permeation performance of indomethacin.

Background and purpose: The utilization of doxorubicin (DOX) in clinal trials is also challenging owing to its adverse effects, including low oral bioavailability, generation of reactive oxygen species (ROS), cardiotoxicity, and epithelial barrier damage. Recently, scavenging of ROS reduced the cytotoxicity of DOX, suggesting a new approach for using DOX as an anticancer treatment. Thus, in this study, non-silica and silica redox nanoparticles (denoted as RNP^N and siRNP, respectively) with ROS scavenging features have been designed to encapsulate DOX and reduce its cytotoxicity.

Experimental approach: DOX-loaded RNP^N (DOX@RNP^N) and DOX-loaded siRNP (DOX@siRNP) were prepared by co-dissolving DOX with RNP^N and siRNP, respectively. The size and stability of nanoparticles were characterized by the dynamic light scattering system. Additionally, encapsulation efficiency, loading capacity, and release profile of DOX@RNP^N and DOX@siRNP were identified by measuring the absorbance of DOX. Finally, the cytotoxicity of DOX@RNP^N and DOX@siRNP against normal murine fibroblast cells (L929), human hepatocellular carcinoma cells (HepG2), and human breast cancer cells (MCF-7) were also investigated.

Key results: The obtained result showed that RNP^N exhibited a pH-sensitive character while silanol moieties improved the stability of siRNP in physiological conditions. DOX@RNP^N and DOX@siRNP were formed at several tens of nanometers in diameter with narrow distribution. Moreover, DOX@siRNP stabilized under different pH buffers, especially gastric pH, and improved encapsulation of DOX owing to the addition of silanol groups. DOX@RNP^N and DOX@siRNP maintained anticancer activity of DOX against HepG2, and MCF-7 cells, while their cytotoxicity on L929 cells was significantly reduced compared to free DOX treatment.

Conclusion: DOX@RNP^N and DOX@siRNP could effectively suppress the adverse effect of DOX, suggesting the potential to become promising nanomedicines for cancer treatments.

Background and purpose: The pandemic of COVID-19 has highlighted the need for managing infectious diseases, which spreads by airborne transmission leading to serious health, social, and economic issues. SARS-CoV-2 is an enveloped virus with a 60-140 nm diameter and particle-like features, which majorly accounts for this disease. Expanding diagnostic capabilities, developing safe vaccinations with long-lasting immunity, and formulating effective medications are the strategies to be investigated.

Experimental approach: For the literature search, electronic databases such as Scopus, Google Scholar, MEDLINE, Embase, PubMed, and Web of Science were used as the source. Search terms like 'Nano-mediated PDT,' 'PDT for SARS-CoV-2', and 'Nanotechnology in treatment for SARS-CoV-2' were used. Out of 275 initially selected articles, 198 were chosen after the abstract screening. During the full-text screening, 80 papers were excluded, and 18 were eliminated during data extraction. Preference was given to articles published from 2018 onwards, but a few older references were cited for their valuable information.

Key results: Synthetic nanoparticles (NPs) have a close structural resemblance to viruses and interact greatly with their proteins due to their similarities in the configurations. NPs had previously been reported to be effective against a variety of viruses. In this way, with nanoparticles, photodynamic therapy (PDT) can be a viable alternative to antibiotics in fighting against microbial infections. The protocol of PDT includes the activation of photosensitizers using specific light to destroy microorganisms in the presence of oxygen, treating several respiratory diseases.

Conclusion: The use of PDT in treating COVID-19 requires intensive investigations, which has been reviewed in this manuscript, including a computational approach to formulating effective photosensitizers.

Background and purpose: The development of vaccines against the SARS-CoV-2 virus has become a big challenge for many countries in 2020-2022. mRNA vaccines were shown to be effective and safe and have been widely used worldwide in the fight against the COVID-19 pandemic. The fundamental factor in creating mRNA vaccines, which ensures effective delivery of mRNA to the host cells, is the composition of lipid nanoparticles, namely the presence of ionized charged lipids, which ensures the binding of mRNA molecules. However, the significant role of liposomes in the development of liposomal vaccines and identification of immunochemical reactions involving lipids should be assessed in the context of the development of the pioneering idea of August Wassermann about the use of liposomal antigens in the diagnosis and immunoprophylaxis of serious human diseases.

Experimental approach: The review is devoted to the use of liposomal antigens as antigen-delivery systems for diagnosis and immunoprophylaxis.

Key results: Studies of cardiolipin antigen in serodiagnosis of syphilis became the foundation of antibodies in diagnosing various infectious diseases and pathological conditions, such as tuberculosis, lupus erythematosus, COVID-19, borreliosis, etc. Identification of antiphospholipid antibodies (mainly anticardiolipin) and today is the most important diagnostic tool for antiphospholipid syndrome.

Conclusion: The liposomal system first proposed in 1906 for the diagnosis of syphilis evolved more than a century later into mRNA vaccines, which are used today in the fight against the COVID-19 pandemic.

Background and purpose: Polycaprolactone nanocapsules incorporated with triazole derivatives in the presence and absence of selenium nanoparticles were prepared and evaluated as antiproliferative and anticancer agents. Polycaprolactone nanoparticles were prepared using the emulsion technique.

Experimental approach: The prepared capsules were characterized using FT-IR, TEM and DLS measurements. The synthesized triazolopyrimidine derivative in the presence and absence of selenium nanoparticles encapsulated in polycaprolactone was tested for its in vitro antiproliferative efficiency towards human breast cancer cell line (MCF7) and murine fibroblast normal cell line (BALB/3T3) in comparison to doxorubicin as a standard anticancer drug.

Key results: The results indicated that encapsulated polycaprolactone with selenium nanoparticles (SeNPs) and triazole-SeNPs were the most potent samples against the tested breast cancer cell line (MCF7). On the other hand, all compounds showed weak or moderate activities towards the tested murine fibroblast normal cell line (BALB/3T3).

Conclusion: As the safety index (SI) was higher than 1.0, it expanded the way for newly synthesized compounds to express antiproliferative efficacy against tumour cells. Hence, these compounds may be considered promising ones. However, they should be examined through further in-vivo and pharmacokinetic studies.

Background and purpose: The widely-used and practically insoluble diprotic acidic dye, bromothymol blue (BTB), is a neutral molecule in strongly acidic aqueous solutions. The Schill (1964) extensive solubility-pH measurement of bromothymol blue in 0.1 and 1.0 M NaCl solutions, with pH adjusted with HCl from 0.0 to 5.4, featured several unusual findings. The data suggest that the difference in solubility of the neutral-form molecule in 1M NaCl is more than 0.7 log unit lower than the solubility in pure water. This could be considered as uncharacteristically high for a salting-out effect. Also, the study reported two apparent values of pK_a1, 1.48 and 1.00, in 0.1 M and 1.0 M NaCl solutions, respectively. The only other measured value found for pK_a1 in the literature is -0.66 (Gupta and Cadwallader, 1968).

Experimental approach: It was reasoned that the there can be only a single pK_a1 for BTB. Also, it was hypothesized that salting-out alone might not account for such a large difference in solubility observed at the two levels of salt. A generalized mass action approach incorporating activity corrections for charged species using the Stokes-Robinson hydration equation and for neutral species using the Setschenow equation, was selected to analyze the Schill solubility-pH data to seek a rationalization of these unusual results.

Key results: BTB reveals complex speciation chemistry in saturated aqueous solutions which had been poorly understood for many years. The appearance of two different values of pK_a1 at different levels of NaCl and the anomalously high value of the empirical salting-out constant could be rationalized to normal values by invoking the formation of a very stable neutral dimer (log K₂ = 10.0 ± 0.1 M^-1). A 'normal' salting-out constant, 0.25 M^-1 was then derived. It was also possible to estimate the 'self-interaction' constant. The data analysis in the present study critically depended on the pK_a1 = -0.66 reported by Gupta and Cadwallader.

Conclusion: A more reasonable salting-out constant and a consistent single value for pK_a1 have been determined by considering a self-interacting (aggregation) model involving an uncharged form of the molecule, which is likely a zwitterion, as suggested by literature spectrophotometric studies.

Background and purpose: Propolis has high potential beneficial bioactive properties such as anti-oxidative, antimicrobial, and anti-tumour activities. However, the bitter taste and the insolubility nature of propolis in water lead to some limitations in their usage in functional food applications.

Experimental approach: Herein, we evaluated the effects of nanoencapsulation of propolis at the different concentration levels (0, 0.4, 0.8, 1.0, and 1.2 %) into the polyvinyl alcohol (PVA) nanoparticles using the electrospraying method, on the structural, physical, antioxidant, antimicrobial and thermal properties.

Key results: The results revealed that the fabricated nanocapsules (PVA-NPs) obtained under optimal conditions had uniform size distribution and unstable particles with small particle size between 104-258 nm, a polydispersity index <0.317, and a zeta potential between -5 and +5 mV. The maximum encapsulation efficiency of PVA-NPs was about 25.32 % for 1 % of the initial propolis loading level. DSC thermal experiments showed an increase in the thermal stability of the propolis loaded PVA nanoparticles as compared to the neat PVA nanoparticles. The percent inhibition of DPPH radical scavenging activity of the nanocapsules was between 80 and 89 %. SEM analysis revealed that PVA-NPs had a spherical shape with a rough surface and were composed of long and thin fibres at nanometric diameters. FT-IR analysis showed that no indications of any chemical reactions were found between the constituents of the core and wall material due to their physical mixing. Antibacterial efficacy was evaluated by the Broth dilution method and PVA-NPs exhibited good inhibitory activity against S. aureus at low concentration ratios, whereas it had no inhibitory activity against E. coli O157:H7.

Conclusion: PVA-NPs fabricated using the electrospraying technique can be used for the development of a new promising natural and bioactive agent in the food and pharmaceutical industry.

Background and purpose: Modern technologies are making advanced paths to address emerging issues. The development of carbon dots (CDs) technology at a tiny level has been researched to have made impeccable strides in advancing the modern scientific field, especially in nanomedicine.

Experimental approach: Researchers have gained much attention on CDs of their unique properties in the synthesis, easy surface modifications, excellent optical properties, low toxicity, and water solubility. Doping carbon dots with other elements makes them more convenient for their use in the medical sector.

Key results: The manuscript provides a detailed discussion of the two main methods, including the hydrothermal pathway. CDs are synthesized bottom-up by building up molecules at the atomic scale and top-down by transforming large carbon particles into nanoscale dimensions.

Conclusion: The present article discussed the role, importance, and recent advancements in the synthesis of CDs, by using various approaches giving importance to the hydrothermal process. Recent investigations, their mechanism, and theranostic applications have also been reported.

Reliable, rapid, highly selective and sensitive analytical methods for the determination of antineoplastic agent 5-fluorouracil (5-FU) in human body fluids (blood serum/plasma and urine) are required to improve the chemotherapy regimen to reduce its toxicity and improve efficacy. Nowadays, electrochemical techniques provide a powerful analytical tool for 5-FU detection systems. This comprehensive review covers the advances in the development of electrochemical sensors for the quantitative determination of 5-FU, mainly focused on original studies reported from 2015 to date. We have summarized recent trends in the electrochemical sensor systems applied for the analysis of 5-FU in pharmaceutical formulations and biological samples, and critically evaluated the key performance metrics of these sensors (limit of detection, linear range, stability and recovery). Challenges and future outlooks in this field have also been discussed.