Anionic Drugs Research Articles

Construction and Evaluation of pH‐Responsive Nitrogen‐Containing Metal–Organic Frameworks as Oral Drug Carriers

ABSTRACTMetal–organic framework (MOF) is a porous material composed of metal ions/clusters and organic ligands. It has attracted much attention due to its high specific surface area, good biocompatibility, chemical modifiability, and diversity of components. Among many MOFs, zirconium‐based MOFs are particularly suitable for biological applications due to their optimal stability and low toxicity to hydrolysis. However, due to the weak coordination bonds between many metal clusters and organic ligands, most MOFs are prone to collapse in acidic environments, and the stability of MOFs as drug carriers cannot be guaranteed so that they cannot be widely used as oral drug carriers. This study synthesized the three MOFs using metal Zr ion clusters as the center and different nitrogen‐containing organic ligands, which are stable in gastric acid, namely, UiO‐66‐PDC, UiO‐66‐NH2, and UiO‐66‐NO2. The anionic drug loxoprofen (LOX) was loaded and characterized using scanning electron microscopy, infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and x‐ray diffraction. The adsorption and release behaviors of LOX and the three MOFs were studied from the molecular point of view by computer simulation. A series of behaviors and mechanisms of pH‐responsive nitrogen‐containing MOFs as oral drug carriers were further explored through rat pharmacokinetic experiments, the everted gut sac experiments, and intestinal absorption mechanism experiments. The experimental results show that there is a strong electrostatic interaction between anionic drug LOX and UiO‐66‐PDC under simulated gastric acid environment, which prolongs the half‐life of the drug, proving that LOX@UiO‐66‐PDC is a promising new oral drug delivery system.

Lab-on-a-chip paper-based electrochemically assisted solid-phase microextraction and ion selective sensor for determination of naproxen in biological fluid samples

BackgroundThe integration of paper-based analytical devices with lab-on-a-chip technology has opened up new possibilities for miniaturized, rapid, low cost and portable diagnostic testing in resource limited settings. This work introduces an integrated lab-on-a-chip platform coupling paper-based analytical devices (LOC-PADs) for dual usage: electrochemically controlled solid-phase microextraction (EC-SPME) and determination of naproxen (NAP) by potentiometric ion-selective electrode (ISE) in biological samples. ResultsConductive papers were successfully fabricated by a chemical procedure. Thereupon, a conducting molecularly imprinted polymer (CMIP) film based on PPy and an anionic model drug (NAP) as a template were applied to the conductive paper substrate via electrochemical methods. A microfluidic chip device was employed to assess the analytical performance of the fabricated paper-based CMIP. The designed chip is divided into two parts with a microfluidic channel between them. The first chamber is an extraction zone for EC-SPME of NAP by using the CMIP paper as a selective sorbent. The second chamber is the detection zone and consists of a paper-based NAP ion selective sensor for potentiometric detection of drug. The analytical process was investigated and optimized for each chamber. Remarkable selectivity towards NAP was achieved in the concentration range from 4.0 × 10−7 to 1.0 × 10−2 mol L−1 with determination coefficient (R2 = 0.99) and the limit of detection (LOD) was 2.0 × 10−7 mol L−1. Anionic Nernstian compliance was gained −58.5 ± 0.5 mV decade−1, and response time in the detection step was 7s for ISE. Satisfactory spiking recovery values within the acceptable range of 90–110 % with RSDs ≤7 % were achieved for the analysis of real samples with fully portable LOC device. SignificanceThe LOC-PADs were favorably used for selective extraction and determination of NAP in serum and saliva samples, respectively. EC-SPME caused sample clean-up, reduced or eliminated different interferences and enhanced selective response of ISE as detection zone of device. Integration of EC-SPME and ISE in a single chip enabled easy and fast determination of trace amounts of NAP in limited real sample volumes, and fully portable advantages.

Competitive sorption of two anionic drugs on chitosan

Competitive sorption of two anionic drugs on chitosan

MgSiO3 Fiber Membrane Scaffold with Triggered Drug Delivery for Osteosarcoma Synergetic Therapy and Bone Regeneration.

In this research, a novel MgSiO3 fiber membrane (MSFM) loaded with indocyanine green (ICG) and doxorubicin (DOX) was prepared. Because of MgSiO3's unique lamellar structure composed of a silicon-oxygen tetrahedron, magnesium ion (Mg2+) moves easily and can be further replaced with other cations. Therefore, because of the positively charged functional group of ICG, MSFM has a rather high drug loading for ICG. In addition, there is electrostatic attraction between DOX (a cationic drug) and ICG (an anionic drug). Hence, after loading ICG, more DOX can be adsorbed into MSFM because of electrostatic interaction. The ICG endows the MSFM outstanding photothermal therapy (PTT) performance, and DOX as a chemotherapeutic drug can restrain tumor growth. On the one hand, H+ exchanged with the positively charged DOX based on the MgSiO3 special lamellar structure. On the other hand, the thermal effect could break the electrostatic interaction between ICG and DOX. Based on the above two points, both tumor acidic microenvironment and photothermal effect can trigger DOX release. What's more, in vitro and in vivo antiosteosarcoma therapy evaluations displayed a superior synergetic PTT-chemotherapy anticancer treatment and excellent biocompatibility of DOX&ICG-MSFM. Finally, the MSFM was proven to greatly promote cell proliferation, differentiation, and bone regeneration performance in vitro and in vivo. Therefore, MSFM provides a creative perspective in the design of multifunctional scaffolds and shows promising applications in controlled drug delivery, antitumor performance, and osteogenesis.

Predictions of biorelevant solubility change during dispersion and digestion of lipid-based formulations

Computational approaches are increasingly explored in development of drug products, including the development of lipid-based formulations (LBFs), to assess their feasibility for achieving adequate oral absorption at an early stage. This study investigated the use of computational pharmaceutics approaches to predict solubility changes of poorly soluble drugs during dispersion and digestion in biorelevant media. Concentrations of 30 poorly water-soluble drugs were determined pre- and post-digestion with in-line UV probes using the MicroDISS Profiler™. Generally, cationic drugs displayed higher drug concentrations post-digestion, whereas for non-ionized drugs there was no discernible trend between drug concentration in dispersed and digested phase. In the case of anionic drugs there tended to be a decrease or no change in the drug concentration post-digestion. Partial least squares modelling was used to identify the molecular descriptors and drug properties which predict changes in solubility ratio in long-chain LBF pre-digestion (R2 of calibration = 0.80, Q2 of validation = 0.64) and post-digestion (R2 of calibration = 0.76, Q2 of validation = 0.72). Furthermore, multiple linear regression equations were developed to facilitate prediction of the solubility ratio pre- and post-digestion. Applying three molecular descriptors (melting point, LogD, and number of aromatic rings) these equations showed good predictivity (pre-digestion R2 = 0.70, and post-digestion R2 = 0.68). The model developed will support a computationally guided LBF strategy for emerging poorly water-soluble drugs by predicting biorelevant solubility changes during dispersion and digestion. This facilitates a more data-informed developability decision making and subsequently facilitates a more efficient use of formulation screening resources.

Distinguishing Molecular Properties of OAT, OATP, and MRP Drug Substrates by Machine Learning.

The movement of organic anionic drugs across cell membranes is partly governed by interactions with SLC and ABC transporters in the intestine, liver, kidney, blood-brain barrier, placenta, breast, and other tissues. Major transporters involved include organic anion transporters (OATs, SLC22 family), organic anion transporting polypeptides (OATPs, SLCO family), and multidrug resistance proteins (MRPs, ABCC family). However, the sets of molecular properties of drugs that are necessary for interactions with OATs (OAT1, OAT3) vs. OATPs (OATP1B1, OATP1B3) vs. MRPs (MRP2, MRP4) are not well-understood. Defining these molecular properties is necessary for a better understanding of drug and metabolite handling across the gut-liver-kidney axis, gut-brain axis, and other multi-organ axes. It is also useful for tissue targeting of small molecule drugs and predicting drug-drug interactions and drug-metabolite interactions. Here, we curated a database of drugs shown to interact with these transporters in vitro and used chemoinformatic approaches to describe their molecular properties. We then sought to define sets of molecular properties that distinguish drugs interacting with OATs, OATPs, and MRPs in binary classifications using machine learning and artificial intelligence approaches. We identified sets of key molecular properties (e.g., rotatable bond count, lipophilicity, number of ringed structures) for classifying OATs vs. MRPs and OATs vs. OATPs. However, sets of molecular properties differentiating OATP vs. MRP substrates were less evident, as drugs interacting with MRP2 and MRP4 do not form a tight group owing to differing hydrophobicity and molecular complexity for interactions with the two transporters. If the results also hold for endogenous metabolites, they may deepen our knowledge of organ crosstalk, as described in the Remote Sensing and Signaling Theory. The results also provide a molecular basis for understanding how small organic molecules differentially interact with OATs, OATPs, and MRPs.

Characterization of Human Organic Anion Transporter 4 (hOAT4) and Mouse Oat5 (mOat5) As Functional Orthologs for Renal Anion Uptake and Efflux Transport.

Organic anions (OAs) are compounds including drugs or toxicants that are negatively charged at physiologic pH and are typically transported by organic anion transporters (OATs). Human OAT4 (SLC22A11) is expressed in the apical membrane of renal proximal tubules. Although there is no rodent ortholog of hOAT4, rodents express Oat5 (Slc22a19), an anion exchanger that is also localized to the apical membrane of renal proximal tubule cells. The purpose of this study was to determine the functional similarity between mouse Oat5 and human OAT4. Chinese hamster ovary (CHO) cells expressing SLC22A11 or Slc22a19 were used to assess the transport characteristics of radiolabeled ochratoxin (OTA). We determined the kinetics of OTA transport; the resulting Michaelis constant (Kt) and maximal rate of mediated substrate transport (Jmax) values were very similar for both hOAT4 and mOat5: Kt 3.9 and 7.2 μM, respectively, and Jmax 4.4 and 3.9 pmol/cm2, respectively. For the profile of OTA inhibition by OAs, IC50 values were determined for several clinically important drugs and toxicants. The resulting IC50 values ranged from 9 μM for indomethacin to ∼600 μM for the diuretic hydrochlorothiazide. We measured the efflux of OTA from preloaded cells; both hOAT4 and mOat5 supported the efflux of OTA. These data support the hypothesis that OAT4 and Oat5 are functional orthologs and share selectivity for OTA both for reabsorption and secretion. SIGNIFICANCE STATEMENT: This study compares the selectivity profile between human organic anion transporter (OAT4) and mouse Oat5. Our data revealed a similar selectivity profile for ochratoxin A (OTA) reabsorption and secretion by these two transporters, thereby supporting the hypothesis that hOAT4 and mOat5, although not genetic orthologs, behave as functional orthologs for both uptake and efflux. These data will be instrumental in selecting an appropriate animal model when studying the renal disposition of anionic drugs and toxicants.

Using the Dynamic Well-Stirred Model to Extrapolate Hepatic Clearance of Organic Anion-Transporting Polypeptide Transporter Substrates without Assuming Albumin-Mediated Hepatic Drug Uptake.

Extrapolating in vivo hepatic clearance from in vitro uptake data is a known challenge, especially for organic anion-transporting polypeptide transporter (OATP) substrates, and the well-stirred model (WSM) commonly yields systematic underpredictions for those anionic drugs, hypothetically due to "albumin-mediated hepatic drug uptake". In the present study, we demonstrate that the WSM incorporating the dynamic free fraction (f D), a measure of drug protein binding affinity, performs reasonably well in predicting hepatic clearance of OATP substrates. For a selection of anionic drugs, including atorvastatin, fluvastatin, pravastatin, rosuvastatin, pitavastatin, cerivastatin, and repaglinide, this dynamic well-stirred model (dWSM) correctly predicts hepatic plasma clearance within 2-fold error for six out of seven OATP substrates examined. The geometric mean of clearance ratios between the predicted and the observed values falls in the range of 1.21-1.38. As expected, the WSM with unbound fraction (f u) systematically underpredicts hepatic clearance with greater than 2-fold error for five out of seven drugs, and the geometric mean of clearance ratios between the predicted and the observed values is in the range of 0.20-0.29. The results suggest that, despite its simplicity, the dWSM operates well for transporter-mediated uptake clearance, and that clearance under-prediction of OATP substrates may not necessarily be associated with the chemical class of the anionic drugs, nor is it a result of albumin-mediated hepatic drug uptake as currently hypothesized. Instead, the superior prediction power of the dWSM confirms the utility of the dynamic free fraction in clearance prediction and the importance of drug plasma binding kinetics in hepatic uptake clearance. SIGNIFICANCE STATEMENT: The traditional well-stirred model (WSM) consistently underpredicts organin anion-transporting polypeptide transporter (OATP)-mediated hepatic uptake clearance, hypothetically due to the albumin-mediated hepatic drug uptake. In this manuscript, we apply the dynamic WSM to extrapolate hepatic clearance of the OATP substrates, and our results show significant improvements in clearance prediction without assuming albumin-mediated hepatic drug uptake.

Fabrication of flexible paper-based conducting molecularly imprinted polymer as analytical devices: Electrochemically assisted solid phase microextraction and selective flexible sensor for determination of naproxen

An electrochemical method is presented for the preparation of paper-based conductive molecular imprinted polymer (CMIP) film as a recognition element of a sensor and a selective absorber in separation methods. The paper became conductive by chemically incorporating polypyrrole (PPy) doped with anion dopant. The effects of the anion dopant and oxidant type on the conductivity of the modified paper were studied. Afterward, a CMIP film based on PPy and an anionic drug as a template was electrochemically synthesized on conductive paper surface, which was then utilized as a selective sorbent for electrochemically assisted solid phase microextraction (EC-SPME) and a recognition element in fabricating flexible drug-selective sensor. Factors affecting the performance of the paper-based EC-SPME device were studied in naproxen (NAP) analysis. All quantitative analytical parameters in the EC-SPME device were obtained by UV–vis absorption spectroscopy. Under the optimal conditions, linearity was achieved within the range of 2.0 × 10−7–2.0 × 10−5 mol/L with determination coefficient (R2 = 0.99) and the limit of detection (LOD) was 0.6 × 10−7mol/L. Moreover, a fabricated paper-based NAP-selective sensor, showed Nernstian response slopes of −61.6 ± 0.5 mV decade−1 over the linear range of 4.0 × 10−7–1.0 × 10−2 mol/L and LOD was 2.0 × 10−7 mol/L. The applicability and efficiency of the paper-based analytical devices were investigated for NAP determination as a model drug in human serum samples. The recoveries were obtained in the range of 90.0–103.0 %. Accordingly, paper-based CMIPs were found to be a novel fabrication method for efficient, selective, flexible and cost-effective material for analytical devices.

A 3D Phosphorescent Supramolecular Organic Framework in Aqueous Solution

AbstractSupramolecular organic framework (SOF) has recently garnered significant research interest in the field of luminescent materials. However, SOF with room‐temperature phosphorescence emission in solution is very rare due to the quenching of dissolved oxygen and free molecular motions, which would lead to nonradiative deactivation of triplet exciton in liquid state. In this work, a 3D cationic phosphorescent SOF is synthesized through host‐guest interaction between CB[8] and a tetrahedral monomer TBBP, which can rapidly adsorb anionic guests in solution. When anionic dyes are introduced, triplet to singlet Förster resonance energy transfer (TS‐FRET) in solution can be achieved, and delayed fluorescence with large Stokes shift can be realized. Additionally, when anionic drugs are introduced, the phosphorescence of TBBP‐CB[8] can be quenched due to charge transfer, enabling the detection of drugs through phosphorescence signals. Taking advantage of the fast adsorption property of 3D SOF, an INHIBIT logic gate with three inputs and two outputs is constructed. These findings provide a novel method to prepare phosphorescent functional materials and a new pathway to construct TS‐FRET system in solution.

Mixed host co-assembled systems for broad-scope analyte sensing.

Here we report a systems chemistry oriented approach for developing information-rich mixed host chemosensors. We show that co-assembling macrocyclic hosts from different classes, DimerDye sulfonatocalix[4]arenes and cucurbit[n]urils, effectively increases the scope of analyte binding interactions and therefore, sensory outputs. This simple dynamic strategy exploits cross-reactive noncovalent host-host complexation interactions while integrating a reporter dye, thereby producing emergent photophysical responses when an analyte interacts with either host. We first demonstrate the advantages of mixed host co-assembled chemosensors through an increased detection range of hydrophobic, cationic, neutral, and anionic drugs. We then implement mixed host sensors in an array-based platform for the differentiation of illicit drugs, including cannabinoids, benzodiazepine analogs, opiates, anesthetics, amphetamine, and common adulterating substances. Finally, the potential of this approach is applied to profiling real-world multi-component illicit street drug samples, proving to be more effective than classical sensor arrays.

Two biocompatible iron-based CPMs for high-capacity adsorption and pH-responsive sustained release of diclofenac sodium

This study focused on synthesizing two iron-based crystalline porous materials (CPMs) with cationic framework and their loading capacities and sustained release behavior for diclofenac sodium (DS), an anionic drug.

Therapeutic coordination polymers: tailoring drug release through metal-ligand interactions.

Developing tunable materials which exhibit sustained drug release is a considerable challenge. Herein, we report the concept of Therapeutic Coordination Polymers (TCPs); non-porous coordination polymers constructed from biocompatible components which demonstrate tunable zero-order drug release kinetics upon degradation of metal-ligand bonds. TCPs were constructed from three principal components: (i) a cationic metal center (M = Mg2+, Mn2+, Zn2+, or Cu2+); (ii) an anionic drug (Diclofenac); and (iii) an alkyl bis-imidazole organic ligand which behaves as a "linker" between metal centers. Most drug-release materials, such as amorphous polymer dispersions, or metal-organic frameworks rely on a diffusion-based mechanism for drug release, but the degradation-controlled release of drugs from non-porous one-periodic coordination polymers has been largely unexplored. TCPs described herein exhibit a high wt% of pharmaceutical (>62%), tailorable zero-order drug release rate kinetics which span over three orders of magnitude, and stimuli-responsive drug release behavior making them well suited for extended drug-release applications.

The Use of Carboxyfluorescein Reveals the Transport Function of MCT6/SLC16A5 Associated with CD147 as a Chloride-Sensitive Organic Anion Transporter in Mammalian Cells

Oral drug absorption involves drug permeation across the apical and basolateral membranes of enterocytes. Although transporters mediating the influx of anionic drugs in the apical membranes have been identified, transporters responsible for efflux in the basolateral membranes remain unclear. Monocarboxylate transporter 6 (MCT6/SLC16A5) has been reported to localize to the apical and basolateral membranes of human enterocytes and to transport organic anions such as bumetanide and nateglinide in the Xenopus oocyte expression system; however, its transport functions have not been elucidated in detail. In this study, we characterized the function of MCT6 expressed in HEK293T cells and explored fluorescent probes to more easily evaluate MCT6 function. The results illustrated that MCT6 interacts with CD147 to localize at the plasma membrane. When the uptake of various fluorescein derivatives was examined in NaCl-free uptake buffer (pH 5.5), the uptake of 5-carboxyfluorescein (5-CF) was significantly greater in MCT6 and CD147-expressing cells. MCT6-mediated 5-CF uptake was saturable with a Km of 1.07 mM and inhibited by several substrates/inhibitors of organic anion transporters and extracellular Cl ion with an IC50 of 53.7 mM. These results suggest that MCT6 is a chloride-sensitive organic anion transporter that can be characterized using 5-CF as a fluorescent probe.

Molecular interactions of cationic/anionic surfactants in presence of anionic antibiotic drug cloxacillin sodium at different temperatures: Micellization and thermodynamic studies

The physicochemical properties and interactions of surfactant–drug aggregates are regarded as essential features to achieve optimum therapeutic action of the drug. In this article, the effect of various concentrations of anionic antibiotic drug cloxacillin sodium (ClxNa) on the micellization of cationic surfactants such as cetyltrimethylammonium bromide (CTAB), tetradecyltrimethylammonium bromide (TTAB) and anionic surfactant sodium dodecyl sulphate (SDS) have been investigated using electrical conductance measurement at different temperatures (288.15 K, 293.15 K, 298.15 K, 303.15 K, 308.15 K, and 313.15 K). The results suggest an increase in critical micelles concentration (CMC) values for cationic surfactants (CTAB/TTAB) with a rise in drug concentration (0 mM up to 10 mM) whereas anionic surfactant SDS shows a decrease in CMC at higher drug concentrations (from 2.5 mM up to 10 mM) at all the studied temperatures. The degree of counterion dissociation (α) values for TTAB aggregates show a slight increase with [ClxNa], except at a few lower temperature ranges whereas such a regular trend was not obtained for CTAB and SDS aggregates. Temperature-dependent CMC values show a nonlinear nature with a rise in temperatures and follow a U-shaped curve for all studied pure surfactant and surfactant–ClxNa systems. Micellization for all surfactant-drug systems is found to be spontaneous. Investigation of other temperature-dependent thermodynamic parameters such as change in standard enthalpy (ΔHm0), and entropy (ΔSm0) of micellization suggest that surfactant–drug interactions are both endothermic (ΔHm0 < 0, particularly at lower temperatures) and exothermic (ΔHm0 < 0, at higher temperatures), whereas micellization is largely entropically driven (ΔSm0 > ΔHm0).

Layered Double Hydroxides as an Intercalation System for Hydrophobic Molecules.

Layered double hydroxides (LDHs) have been extensively studied as drug delivery systems due to their favorable characteristics, including biocompatibility, high loading efficiency, and pH-responsive release. However, the current research predominantly focuses on LDHs as carriers for various anionic drugs, while there are only limited reports on LDHs as carriers for hydrophobic drugs. In this study, we successfully achieved the loading of a hydrophobic drug mimic, Nile red (NR), into LDHs using sodium dodecyl sulfate (SDS) as an intermediate storage medium. Furthermore, we optimized the experimental methods and varied the SDS/NR molar ratio to optimize this intercalation system. With an increase in the SDS/NR molar ratio from 2/1 to 32/1, the loading efficiency of LDH-SDS-NR for NR initially increased from 1.32% for LDH-SDS-NR_2/1 to 4.46% for LDH-SDS-NR_8/1. Then, the loading efficiency slightly decreased to 3.64% for LDH-SDS-NR_16.8/1, but then increased again to 6.31% for LDH-SDS-NR_32/1. We believe that the established method and the obtained results in this study broaden the application scope of LDHs as delivery systems for hydrophobic drugs and contribute to the further expansion of the application scope of LDHs.

In situ synthesis of UV-responsive mesoporous SiO2 drug release systems using the associates of anionic drugs and cationic silica source as templates

In situ synthesis of UV-responsive mesoporous SiO2 drug release systems using the associates of anionic drugs and cationic silica source as templates

Electrically controlled transdermal drug release of ionic and non-ionic drug from kappa-iota carrageenan cryogel

The goals of this study were to fabricate and characterize the kappa (K) and iota (I) carrageenan (CAR) cryogel matrix for electrically controlled transdermal ionic namely diclofenac (DCNa) and non-ionic namely theophylline (Theo) delivery. The CAR cryogels were prepared by freeze-drying method based on the effects of CAR types which were different sulfate ester group content in the structure, K-CAR concentrations, and blending K and I-CAR. According to the results, the increasing K-CAR concentrations affected to reduce the swelling behavior and pore size of cryogels. However, the swelling behavior was increased and pore size was decreased with blending K/I-CAR. The release mechanism of DCNa and Theo was a non-fickian and fickian diffusion depending on drug types, cryogels composition, and applied electric potentials. The amount of drug release was decreased with increasing K-CAR concentrations and decreased with a blending K/I-CAR. However, the amount of drug release was increased with increasing electric potential, especially an anionic drug. The amount of DCNa was higher than that of Theo with and without applied electric potential. The maximum amount of drug release was 78.06 and 58.78% for DCNa and Theo, respectively. Thus, the CAR cryogel is suitable for controlled release of ionic and non-ionic drug with and without applied electric field.

Examining layer‐by‐layer assembly of polyelectrolyte‐drug interactions using Quartz Crystal Microbalance with Dissipation

AbstractThe incorporation of drug molecules into layer‐by‐layer (LbL) assemblies attracts great interest in biomedical applications. This work describes the preparation and characterization of LbL multilayers including drugs, namely ibuprofen (IBF‐Na) and Diclofenac sodium salt (DCF‐Na) as anionic molecules. The main aim is to enhance the drug loading capacity within the LbL assembly. The effects of drug‐LbL multilayered films obtained from poly(diallyl dimethylammonium chloride) (PDADMAC)/IBF‐Na and PDADMAC/DCF‐Na interactions on multilayer growth and loading of model molecules are examined using UV‐Visible and Quartz‐Crystal Microbalance with Dissipation (QCM‐D). The wet mass of PDADMAC/IBF‐Na is found to be 67.2 ng/cm2, while PDADMAC/DCF‐Na film exhibits 201.6 ng/cm2 mass adsorption. Furthermore, the multilayer stabilities are assessed against neutral, acidic, and basic solutions. The results demonstrate that the LbL films have robustness, without any signs of multilayer degradation. By the way, the incorporation of IBF‐Na into the feed solution leads to the formation of a rigid structure, whereas the inclusion of DCF‐Na results in a comparatively flexible structure. The use of a higher molecular weight and more polar drug in the feed causes a noticeable rise in surface hydrophilicity and surface roughness. PDADMAC/IBF‐Na and PDADMAC/DCF‐Na display average contact angles of 46 ± 1.3° and 76 ± 2° while they have roughness values of 5.9 and 8.0 nm, respectively. LbL multilayers fabricated from a polycation and anionic drug can be considered as a promising material platform for controlled drug loading due to their tunable physicochemical and morphological properties as well as surface wettability.

CYTOGENETIC EFFECTS OF SURFACTANTS

Introduction. The widespread use of surfactants in economic activity and life has led to global pollution. The negative impact of surfactants on various characteristics of living organisms has been revealed, which makes a research on the safety of surfactants extremely relevant. Aim. The aim of this work was to study the genotoxic potential of anionic and cationic surfactants. Methods. The influence of anionic (sodium stearate and alkylbenzenesulpho-acid) and cationic (Praepagen TQ) surfactants on the value of the mitotic index, as well as on the regularity of mitosis and meiosis of Triticum aestivum L. cv. Odesa fantasy by standard cytogenetic methods. Main results. Under the action of surfactants in the root meristem of sprouts, the mitotic index significantly decreased and the number of cells containing chromosomal aberrations increased. Among the abnormalities at the ana-telophase stage, cells with lagging chromosomes, fragments, the formation of chromosomal bridges, and complex disorders were observed. These changes were directly proportional to the concentration of the drugs. The action of the cationic drug was less harmful than the action of both anionic drugs. Treatment of plants with surfactants led to a highly reliable increase in the proportion of abnormal MCPs in both the first and second division of meiosis, directly proportional to the concentration of surfactants applied. No differences were found between the first and second meiotic divisions in terms of the frequency of formation of defective MCPs. Both anionic surfactants had a stronger effect than the cationic one; with the use of alkylbenzenesulfonic acid, the degree of violations in microsporocytes was the greatest. Conclusions. A significant decrease in the mitotic index and an increase in the proportion of cells containing chromosomal aberrations in the root meristem of sprouts, as well as a significant increase in the proportion of abnormal MCPs in both the first and second division of meiosis, were found to be directly proportional to the concentration of surfactant. According to all the parameters studied, the action of the cationic drug “Praepagen TQ” was milder than the action of both anionic surfactants.