Gold (III) Derivatives in Colon Cancer Treatment

Cancer is one of the leading causes of morbidity and mortality worldwide. Colorectal cancer (CRC) is the third most frequently diagnosed cancer in men and the second in women. Standard patterns of antitumor therapy, including cisplatin, are ineffective due to their lack of specificity for tumor cells, development of drug resistance, and severe side effects. For this reason, new methods and strategies for CRC treatment are urgently needed. Current research includes novel platinum (Pt)- and other metal-based drugs such as gold (Au), silver (Ag), iridium (Ir), or ruthenium (Ru). Au(III) compounds are promising drug candidates for CRC treatment due to their structural similarity to Pt(II). Their advantage is their relatively good solubility in water, but their disadvantage is an unsatisfactory stability under physiological conditions. Due to these limitations, work is still underway to improve the formula of Au(III) complexes by combining with various types of ligands capable of stabilizing the Au(III) cation and preventing its reduction under physiological conditions. This review summarizes the achievements in the field of stable Au(III) complexes with potential cytotoxic activity restricted to cancer cells. Moreover, it has been shown that not nucleic acids but various protein structures such as thioredoxin reductase (TrxR) mediate the antitumor effects of Au derivatives. The state of the art of the in vivo studies so far conducted is also described.

Melatonin/Cyclodextrin Inclusion Complexes: A Review

Melatonin (MLT) is involved in many functions of the human body, mainly in sleeping-related disorders. It also has anti-oxidant potential and has been proven very effective in the treatment of seasonal affective disorders (SAD), which afflict some people during short winter days. Melatonin has been implicated in a range of other conditions, including Parkinson’s disease, Alzheimer’s and other neurological conditions, and in certain cancers. Its poor solubility in water leads to an insufficient absorption that led scientists to investigate MLT inclusion in cyclodextrins (CDs), as inclusion of drugs in CDs is a way of increasing the solubility of many lipophilic moieties with poor water solubility. The aim of this review is to gather all the key findings on MLT/CD complexes. The literature appraisal concluded that MLT inclusion leads to a 1:1 complex with the majority of CDs and increases the solubility of the hormone. The interactions of MLT with CDs can be studied by a variety of techniques, such as NMR, FT-IR, XRD and DCS. More importantly, the in vivo experiments showed an increase in the uptake of MLT when included in a CD.

The improvement of biocompatibility by incorporating porphyrins into carbon dots with photodynamic effects and pH sensitivities

Photodynamic therapy (PDT) is a promising new treatment for cancer; however, the hydrophobic interactions and poor solubility in water of photosensitizers limit the use in clinic. Nanoparticles especially carbon dots have attracted the attention of the world’s scientists because of their unique properties such as good solubility and biocompatibility. In this paper, we integrated carbon dots with different porphyrins to improve the properties of porphyrins and evaluated their efficacy as PDT drugs. The spectroscopic characteristics of porphyrins nano-conjugates were studied. Singlet oxygen generation rate and the light- and dark-induced toxicity of the conjugates were studied. Our results showed that the covalent interaction between CDs and porphyrins has improved the biocompatibility. The synthesized conjugates also inherit the pH sensitivity of the carbon dots, while the conjugation also decreases the hemolysis ratio making them a promising candidate for PDT. The incorporation of carbon dots into porphyrins improved their biocompatibility by reducing toxicity.

Effect of the clathrate complex of selenopyran and β-cyclodextrin on the rate of healing of a conditionally aseptic full-thickness planar wound in rats

Introduction. Selenopyran is an organic selenium compound with sharply hydrophobic properties. An increase in solubility in water (and as a consequence – and bioavailability) is possible due to the formation of inclusion complexes with cyclodextrins.Aim. The aim of this work was to study the effect of a gel containing a clathrate complex of selenopyran with β-cyclodextrin on the rate of wound healing on a model of a conditionally aseptic full-thickness planar wound in rats.Materials and methods. The object of the study was a gel containing a clathrate complex of selenopyran with β-cyclodextrin (the content of selenopyran in the gel was 0.1 %). A model of a full-thickness planar wound in sexually mature male rats was used. 20 individuals were divided into 2 groups – intact (without treatment) and experimental (received gel treatment). Efficacy was assessed by the change in wound area at 3, 5, 7, 9, 11 and 14 days after application of wound.Results and discussion. The results of the study showed that the relative area of the wounds in the treated animals by the 3rd day of the experiment was less than in the intact ones. On the fifth day of the experiment, the differences were statistically significant (57.49 ± 12.51 % in treated animals versus 85.27 ± 26.61 % in intact animals). By the 14th day of the experiment, there were practically no differences in the groups of animals.Conclusion. The results obtained indicate that when using a gel containing selenopyran in combination with β-cyclodextrin, it accelerates the transition from the inflammation phase to the proliferation phase. This is most likely due to the antioxidant properties of selenopyran. Considering the lower concentration of selenopyran in comparison with the therapeutic concentrations of other antioxidants (taurine, allantoin), it can be considered as a promising wound healing agent for further study.

Study of the technological properties of excipients in the development of the composition of orally dispersible tablets

Introduction. The article presents the results of studying the technological properties of individual excipients widely used in the compositions of existing orally dispersed tablets (ODT) for subsequent planning a multifactorial experiment. Samples of excipients were analyzed according to such pharmacopoeial indicators as description, flowability, bulk density, compressibility, fractional composition, solubility in water.Aim. The aim of the work is to create a list and study the technological properties of candidate substances for the role of auxiliary substances in the composition being developed by the ODT.Materials and methods. The technological properties of excipient samples were studied according to the methods of the State Pharmacopoeia of the XIV edition using the flowability tester GTL (ERWEKA, Germany), the bulk density tester SVM 221 (ERWEKA, Germany), the tablet press PGR-10 (LabTools, Russia) and the tablet hardness tester TBH 125 TDP (ERWEKA, Germany).Results and discussion. As a result of the study, experimental data on the technological properties of excipient samples were collected, and the selected samples were compared according to pharmaceutical and technological indicators.Conclusion. In the course of the study, a list of auxiliary substances for the development of the composition of ODT was formed and studies of their technological properties were carried out. The obtained experimental data will allow to develop an optimal matrix of a multifactorial experiment for the development of the composition of ODT and justify the choice of excipients.

The Water-Soluble Chitosan Derivative, N-Methylene Phosphonic Chitosan, Is an Effective Fungicide against the Phytopathogen Fusarium eumartii

Chitosan has been considered an environmental-friendly polymer. However, its use in agriculture has not been extended yet due to its relatively low solubility in water. N-Methylene phosphonic chitosan (NMPC) is a water-soluble derivative prepared by adding a phosphonic group to chitosan. This study demonstrates that NMPC has a fungicidal effect on the phytopathogenic fungus Fusarium solani f. sp. eumartii (F. eumartii) judged by the inhibition of F. eumartti mycelial growth and spore germination. NMPC affected fungal membrane permeability, reactive oxygen species production, and cell death. Also, this chitosan-derivative exerted antifungal effects against two other phytopathogens, Botrytis cinerea, and Phytophthora infestans. NMPC did not affect tomato cell viability at the same doses applied to these phytopathogens to exert fungicide action. In addition to water solubility, the selective biological cytotoxicity of NMPC adds value in its application as an antimicrobial agent in agriculture.

Investigation of the Feasibility of Ventricular Delivery of Resveratrol to the Microelectrode Tissue Interface

(1) Background: Intracortical microelectrodes (IMEs) are essential to basic brain research and clinical brain–machine interfacing applications. However, the foreign body response to IMEs results in chronic inflammation and an increase in levels of reactive oxygen and nitrogen species (ROS/RNS). The current study builds on our previous work, by testing a new delivery method of a promising antioxidant as a means of extending intracortical microelectrodes performance. While resveratrol has shown efficacy in improving tissue response, chronic delivery has proven difficult because of its low solubility in water and low bioavailability due to extensive first pass metabolism. (2) Methods: Investigation of an intraventricular delivery of resveratrol in rats was performed herein to circumvent bioavailability hurdles of resveratrol delivery to the brain. (3) Results: Intraventricular delivery of resveratrol in rats delivered resveratrol to the electrode interface. However, intraventricular delivery did not have a significant impact on electrophysiological recordings over the six-week study. Histological findings indicated that rats receiving intraventricular delivery of resveratrol had a decrease of oxidative stress, yet other biomarkers of inflammation were found to be not significantly different from control groups. However, investigation of the bioavailability of resveratrol indicated a decrease in resveratrol accumulation in the brain with time coupled with inconsistent drug elution from the cannulas. Further inspection showed that there may be tissue or cellular debris clogging the cannulas, resulting in variable elution, which may have impacted the results of the study. (4) Conclusions: These results indicate that the intraventricular delivery approach described herein needs further optimization, or may not be well suited for this application.

An Overview of Cellulose Derivatives-Based Dressings for Wound-Healing Management

Presently, notwithstanding the progress regarding wound-healing management, the treatment of the majority of skin lesions still represents a serious challenge for biomedical and pharmaceutical industries. Thus, the attention of the researchers has turned to the development of novel materials based on cellulose derivatives. Cellulose derivatives are semi-synthetic biopolymers, which exhibit high solubility in water and represent an advantageous alternative to water-insoluble cellulose. These biopolymers possess excellent properties, such as biocompatibility, biodegradability, sustainability, non-toxicity, non-immunogenicity, thermo-gelling behavior, mechanical strength, abundance, low costs, antibacterial effect, and high hydrophilicity. They have an efficient ability to absorb and retain a large quantity of wound exudates in the interstitial sites of their networks and can maintain optimal local moisture. Cellulose derivatives also represent a proper scaffold to incorporate various bioactive agents with beneficial therapeutic effects on skin tissue restoration. Due to these suitable and versatile characteristics, cellulose derivatives are attractive and captivating materials for wound-healing applications. This review presents an extensive overview of recent research regarding promising cellulose derivatives-based materials for the development of multiple biomedical and pharmaceutical applications, such as wound dressings, drug delivery devices, and tissue engineering.

Adamantane-Substituted Purines and Their β-Cyclodextrin Complexes: Synthesis and Biological Activity

Cyclin-dependent kinases (CDKs) play an important role in the cell-division cycle. Synthetic inhibitors of CDKs are based on 2,6,9-trisubstituted purines and are developed as potential anticancer drugs; however, they have low solubility in water. In this study, we proved that the pharmaco-chemical properties of purine-based inhibitors can be improved by appropriate substitution with the adamantane moiety. We prepared ten new purine derivatives with adamantane skeletons that were linked at position 6 using phenylene spacers of variable geometry and polarity. We demonstrated that the adamantane skeleton does not compromise the biological activity, and some of the new purines displayed even higher inhibition activity towards CDK2/cyclin E than the parental compounds. These findings were supported by a docking study, which showed an adamantane scaffold inside the binding pocket participating in the complex stabilisation with non-polar interactions. In addition, we demonstrated that β-cyclodextrin (CD) increases the drug’s solubility in water, although this is at the cost of reducing the biochemical and cellular effect. Most likely, the drug concentration, which is necessary for target engagement, was decreased by competitive drug binding within the complex with β-CD.

Green Fabrication and Release Mechanisms of pH-Sensitive Chitosan–Ibuprofen Aerogels for Controlled Transdermal Delivery of Ibuprofen

Ibuprofen is a potent non-steroidal anti-inflammatory drug due to its analgesic, antipyretic, and anti-inflammatory actions. However, its poor solubility in water makes it difficult to manufacture ibuprofen tablets, which limited the application of ibuprofen in drug delivery systems. Polymer–drug aerogels have attracted huge interest in optimizing the drug delivery efficiency and improving the physicochemical characteristics and therapeutic quality. Here, chitosan–ibuprofen aerogels with excellent swelling, high biocompatibility, and better drug delivery efficiency were synthesized by a simple method. Our study found that the chitosan–ibuprofen aerogels exhibited remarkably improved thermal stability, excellent swelling ratio, and high drug loading. As a consequence of these favorable properties, the chitosan–ibuprofen aerogels exhibited improved drug delivery efficiency and achieved drug prolonged administration. Our study highlights the great potential of polymer–drug aerogels in improving the drug delivery efficiency of transdermal drug delivery systems.