Poor drug solubility or loading, inflexible drug release profiles, and poor storage stability are some of the most difficult issues to surpass in the production of efficient and safe controlled delivery systems. So, due to their suitable properties, ionic liquids (ILs) may be used as new functional materials to overcome these drawbacks. ILs are organic salts, which may be introduced in different types of drug delivery systems.

Herein, 5 ILs — two imidazole-based and three choline-aminoacid —were synthesized and their applicability as functional materials in drug delivery systems, at non-toxic concentrations, was evaluated.

Firstly, their cytotoxicity in human keratinocytes (HaCaT) was evaluated, and considering these results, it was developed the controlled drug delivery systems in the presence and absence of the ILs. Each IL was incorporated at the upper concentration of these salts allowing the maintenance of cell viability. Lipidic implants and transfersomes without and with IL (TransfersomILs) were the chosen lipid-based controlled delivery systems to investigate the impact of adding ILs. In these studies, rutin was used as a model drug with poor aqueous solubility.

Our results showed that the ILs promoted a significantly higher drug loading, with the choline-based ILs displaying better results when compared with the imidazole-based ILs. The incorporation of ILs showed that they seem to modulate the release profile of the drug from the lipidic implants. Regarding TransfersomILs, they demonstrated a higher association efficiency with a higher total amount of drug release, and better colloidal and storage stability when compared with the transfersomes without ILs.

In conclusion, the incorporation of ILs, at non-toxic concentrations, allowed the development of more efficient controlled delivery systems, showing that ILs may be multifunctional and valuable materials to boost the performance of delivery systems.

“Pineapple” is one of the most popular varieties of apricot (Armeniaca vulgaris L.). However, this variety was first obtained in Yerevan (Armenia), where it is called Shalakh or Yerevanian. It has been cultivated throughout Armenia for many centuries. Despite its great popularity the chemical composition, pharmacological properties and use of raw materials from its historical territory and the usual conditions of germination have not been studied before. Apricot seeds are a source for obtaining the oil, which is used as a cosmetic and medicinal product. These effects are mainly caused by the high content of unsaturated fatty acids. Probably, fruits should also be characterized by a high content of unsaturated fatty acids.

The aim of this study was to investigate the fatty acid profile and the content of unsaturated fatty acids in the fruits of the apricot variety Shalakh, collected and harvested in 2020 in the Armavir region in Armenia. The fatty acid composition of the raw material was determined by gas-liquid chromatography with a flame ionization detector on a Shimadzu GC-2014B chromatograph.

As a result of the study, 6 saturated fatty acids (lauric, myristic, palmitic, stearic, arachinic, behenic) and 5 unsaturated fatty acids (palmitoleic, oleic, vaccenic, linoleic, α-linolenic) were found in apricot fruit. The highest content of these compounds is oleic acid - 40.18% and linoleic acid - 35.10%.

The ratio of unsaturated fatty acids to saturated was 4.6:1. We can suggest that the raw materials of the Shalakh apricot variety may have reparative, antioxidant and rejuvenating properties.

Pseudomonas aeruginosa is an opportunistic and nosocomial pathogen associated with respiratory tract infections. Due to the irrational use of antibiotics, P. aeruginosa has developed antibiotic resistance, resulting in increased morbidity and mortality rates. Medicinal plants of reported antibacterial activity can be alternatively used to treat its infections and do not result in resistance. The purpose of our study was to check for the antibiofilm potential of Juglans regia L. (Persian walnut) extracts against waterborne P. aeruginosa. The aqueous and methanol extracts were checked for antibacterial activity by agar well diffusion method. The biofilm formation assay carried out for the plant extracts gave MIC values of 3 and 5 µg/ml for P. aeruginosa strains. The thin layer chromatography (TLC), revealed the active components in the form of two bands. Our study indicated that the native plants of Pakistan have bioactivity against biofilm-forming pathogens.

The family of abietane-type diterpenoids has long attracted natural product researchers, biochemists, organic and medicinal chemists with endless discoveries in terms of isolations, characterization, pharmacology, biosynthesis, chemical synthesis and medicinal chemistry. In our group, we have developed over the last decade a number of studies towards the semisynthesis of a variety of aromatic abietanes as well as biological screenings. The diterpene ferruginol is a very simple phenolic abietane which has demonstrated a plethora of promising biological and pharmacological properties. Some years ago, we developed a multigram semisynthetic procedure to obtain ferruginol itself from the commercially available (+)-dehydroabietylamine, also called leelamine. Over the years, we have investigated ferruginol and related analogues synthesized by us, with the aim of extending the pharmacological knowledge of this unique molecule and characteristic carbon framework and unveil their potential application. In this communication, we disclose how a simple modification in the carbon skeleton of ferruginol such as the introduction of an amino group can lead to a more potent analogue, 18-aminoferruginol or 12-hydroxydehydroabietylamine, in human breast cancer and melanoma cell lines and also changes in the mechanism of action as compared to the parent molecule. This outcome may set a platform for the development of novel anticancer agents based on natural products.

Purpose: Direct compression is a mostly used and required process in the pharmaceutical industry. The co-processing is the most widely explored method for the preparation of directly compressible excipients. The present research work was targeted to develop a novel directly compressible co-processed excipient to prepare fast disintegrating tablets of Carvedilol.

Methods: From the preliminary trials, Lactose was selected as a directly compressible excipient and sodium starch glycolate was used as a super disintegrant. PEG 4000 was used as the binder from the preliminary batches. A melt agglomeration technique was selected to prepare the suitable co-processed excipient. Co-processed excipient was optimized by a central composite design where the concentration of binder (X1) and concentration of disintegrant (X2) was selected as independent variables from the preliminary studies. Carr’s index, wetting time, disintegration time, and Friability were selected as dependent variables as they were having the highest effect on co-processed excipient and tablet properties.

Results: The optimized co-processed excipient was characterized by Kawakita’s and Kuno’s analysis, Heckel plot analysis, granular friability index, and lubricant sensitivity ratio. Results of dilution potential revealed that poorly compressible drug; Carvedilol was sufficiently incorporated into co-processed excipient for the preparation of fast-disintegrating tablets. An in-vitro dissolution study showed faster disintegration of the drug compared to the conventional tablets. Instrumental studies like FT-IR and DSC proved the compatibility of various materials with each other.

Conclusion: The present investigation underlines the fact that co-processing may be adopted for the development of directly compressible adjuvant for the use in pharmaceuticals.

Neuroendocrine neoplasms (NENs) are tumors arising from cells of the endocrine and nervous systems, found in various organs. Both nitrotyrosine and asymmetric dimethylarginine (ADMA) have significant effects on carcinogenesis, inducing oxidative and nitrosative stress and changes in proteins, lipids, and DNA. This study aimed to assess nitrotyrosine and ADMA levels in NEN patients based on tumor location, potentially improving diagnostic and therapeutic approaches.

Participants were divided into two subgroups, each with 10 patients. The first subgroup had pancreatic NENs (P-NENs), and the second had lung NENs (L-NENs). Venous blood samples were collected and processed to obtain blood serum. Nitrotyrosine and ADMA levels were measured using enzyme-linked immunosorbent assay (ELISA) tests. Results are presented as mean values with ± standard error of the mean (SEM). A p-value less than 0.05 was considered statistically significant.

In the P-NEN group, nitrotyrosine averaged 495.888 ± 105.538 nmol/L, while the L-NEN group had levels of 561.587 ± 158.929 nmol/L. The ADMA concentration was 0.378 ± 0.027 µmol/L in the P-NEN patients and 0.346 ± 0.013 µmol/L in the L-NEN group. Statistical analysis revealed no significant differences between the two groups for both analytes. Based on current findings, tumor location does not significantly impact nitrotyrosineand ADMA levels in NEN patients. Further research with larger, diverse samples may offer valuable insights into their relationship, potentially enhancing NEN diagnostic and therapeutic approaches.

The development of an amorphous solid dispersion (ASD) is a promising strategy for stabilizing the amorphous form of poorly water-soluble active pharmaceutical ingredients (APIs). An API–polymer temperature–composition (T–C) phase diagram can facilitate a rational approach to successful ASD formulation design. Since it is typically challenging to accurately measure the API solubility in a polymer under ambient conditions, differential scanning calorimetry (DSC) is employed to measure it at elevated temperatures. The experimental dataset is subsequently extrapolated to lower temperatures of interest using a solid-liquid equilibrium (SLE) curve modeling approach (e.g., the PC-SAFT equation of state (EOS)). However, the currently followed DSC-based protocols (e.g., the melting point depression (MPD) method) are inefficient and cannot provide reliable data points close to the API–polymer glass-transition temperature line. Hence, the “step-wise dissolution” (S-WD) method was recently developed, which is a new DSC-based protocol that is both cost- and time-effective. The S-WD method was employed to assess the veracity of the purely-predicted PC-SAFT EOS-based SLE curve for more than fifteen API–polymer combinations. In general, the PC-SAFT EOS provided satisfactory qualitative descriptions, but not necessarily accurate quantitative predictions. The identification of different API–polymer case types (i.e., Case I/II/III) based on the pure component physicochemical properties was a key finding, which will play an important role in the future development of ASDs comprising expensive anticancer compounds. Both the S-WD and MPD methods were subsequently modified and an optimal protocol was proposed for each one, which can significantly reduce the required experimental effort.

Conjugation of iron oxide nanoparticles (IONPs) to drugs and antibodies increases contrast during Magnetic Resonance Imaging (MRI). Some IONPs are approved by the Food and Drug Administration for use in vivo as MRI contrast agents. The Cuban Neuroscience Center has a family of compounds derived from naphthalene, called Amylovis^®, to be used in the diagnosis and treatment of Alzheimer's disease. In this work, IONPs with different coatings conjugated with Amylovis^® derivatives were synthesized for their potential use as contrast agents to obtain MRI. The presence of the different coatings was verified by means of signals corresponding to the functional groups present in them with the use of FT-IR. The saturation magnetization values ​​and the magnetic behavior of the nanoparticles were determined by VSM. The DLS profiles made it possible to identify the systems with the smallest hydrodynamic diameter and taking into account the Pot ζ values ​​and the sedimentation study using UV-Vis spectroscopy, it was possible to select the most stable systems over time. The affinity of the coatings that originated more stable nanoparticles for the βA_1-42 peptide was evaluated by molecular docking. Molecular docking showed that the coatings do not affect the interaction of the Amylovis^® derivative with the receptor and the newly incorporated polar groups increased the affinity for the receptor.

The structural and biological importance of steroids makes them ideal molecular building blocks for obtaining molecules of greater complexity and lipophilicity. Hence, its conjugation to other molecules of chemical or biological relevance is a current approach in the search for interesting biomedical and chemical applications. On the other hand, 3,4-dihydro-2(1H)-pyridones are compounds derived from 1,4-dihydropyridines, so they could be used for the treatment of cardiovascular diseases and as antivirals. The search for new compounds for the treatment of this type of disease continues to be of interest. In the present work, the synthesis of new compounds of the steroid-[3,4-dihydro-2(1H)-pyridone] type is reported, using a multicomponent methodology starting from steroidal β-ketoesters. Taking into account that magnetic nanoparticles can be used to activate functional groups such as carbonyls and carboxyls, these were used as heterogeneous catalysts to increase the synthesis yield by 10-25%. To determine the possible application of 3,4-dihydro-2(1H)-pyridones in medicinal chemistry as antivirals, a molecular anchoring study was carried out. The enzymes used were the protease (PL^pro) and the 3-chymotrypsin-like protease (3CL^pro) of SARS-Cov-2. These cysteine proteases play a crucial role in the virus life cycle. The study carried out shows that the affinity of the ligand-enzyme complexes obtained was negative in all clusters (-8 to -10 kcal/mol), which indicates that ligand-enzyme binding is favored. All conjugates form hydrogen bonds with proteases and hydrophobic interactions through the steroidal backbone. The functionalization with steroid moiety is a way to increase the biomolecular recognition areas and increase the strength of the union with the enzymatic receptors.

Hydrogels are carriers of active substances often used in pharmaceutical technology. They are biocompatible with human tissues. They show the ability to absorb biological fluids and have the potential to develop new therapies for the treatment of exudative and chronic wounds. Numerous studies support their potential use as hormone carriers. The aim of our research was to develop a hydrogel containing insulin (INS) for administration on the skin. This hormone exhibits reparative and regenerative effects in lesional tissues. Hydrogel carriers of insulin based on hydroxypropyl methylcellulose (HPMC) and hydroxypropyl methylcellulose (HPMC) with chitosan (CTS) were developed. The insulin concentration (Insulatard Penfill, Novo Nordisk Denmark) was 1mg/g of hydrogel. A paddle apparatus (DT 600, ERWEKA GmbH, Germany) equipped with Enhancer Cell type chambers was used for pharmaceutical availability testing. The semipermeable membrane was a Spectra/Por2 dialysis membrane. Rotational rheometry was used for rheological tests. A Lamy RM 200 Touch laboratory rheometer (Lamy Rheology Instruments, Champagne au Mont d'Or, France) equipped with an MK-CP 2445 measuring system and a CP-1 Plus thermostat was used. Measurements were carried out at 25±1°C. Hydrogel flow curves were determined and the thixotropy effect of the analyzed systems was tested. Graphical and mathematical analysis of the results was carried out using Rheometic-P Software. The study showed that the release of INS from the developed formulations occurred in a prolonged manner. From the HPMC+CTS-based hydrogel formulation, 73% of the INS was released at 6.5 hours, while from the HPMC-based hydrogel, 65% of the INS was released after 5.5 hours. Rheological studies confirmed that the developed hydrogels are non-Newtonian, shear-thinning systems and have a yield stress. The analyzed formulations exhibit thixotropy. After pre-formulation studies, it was concluded that the hydrogels based on HPMC+INS and HPMC+CTS+INS show a high application potential.