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1 H NMR-spectra (D2O, 600 MHz) of MCD (A), MCD-EG, molar ratio 2:1 (B), MCD-Lev-EG, molar ratio 4:1:1 (C). (D) Proposed structure of MCD inclusion complexes with EG, apiol, Lev. 1 H NMR-spectra (D2O, 500 MHz) of HPCD (E), HPCD-apiol, molar ratio 2:1 (F).
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Allylpolyalkoxybenzenes (APABs) and terpenoids from plant essential oils exhibit a range of remarkable biological effects, including analgesic, antibacterial, anti-inflammatory, antioxidant, and others. Synergistic activity with antibiotics of different classes has been reported, with inhibition of P-glycoprotein and impairment of bacterial cell me...
Citations
... Apiol (1-allyl-2,5-dimethoxy-3,4-methylenedioxybenzene), a component of parsley oil, inhibits cytochrome P450 3A4 (IC 50 7.9 µM) [19,36,44,58,[77][78][79][80], which metabolizes xenobiotics in the liver, reducing their bioavailability. Apiol demonstrates weak antibacterial and anticancer activities, but at the same time, it dramatically enhances the effect of antibiotics (for example, moxi-or levofloxacin) [44,77] and cytostatics (doxorubicin, paclitaxel, etc.) [49] by inhibiting P-glycoprotein. ...
... Apiol (1-allyl-2,5-dimethoxy-3,4-methylenedioxybenzene), a component of parsley oil, inhibits cytochrome P450 3A4 (IC 50 7.9 µM) [19,36,44,58,[77][78][79][80], which metabolizes xenobiotics in the liver, reducing their bioavailability. Apiol demonstrates weak antibacterial and anticancer activities, but at the same time, it dramatically enhances the effect of antibiotics (for example, moxi-or levofloxacin) [44,77] and cytostatics (doxorubicin, paclitaxel, etc.) [49] by inhibiting P-glycoprotein. ...
... This can provide the possibility of using aromatic adjuvants (which are otherwise not applicable) as an antitumor agent and to obtain an efficient combined antitumor formulation. CDs and heparin can protect the substance from destruction and inactivation, increase the half-life, and in addition, due to adsorption on cell membranes, increase the membrane permeability [49,77]. ...
Allylbenzenes (apiol, dillapiol, myristicin and allyltetramethoxybenzene) are individual components of plant essential oils that demonstrate antitumor activity and can enhance the antitumor activity of cytotoxic drugs, such as paclitaxel, doxorubicin, cisplatin, etc. Triphenylphosphine (PPh3) derivatives of allylbenzenes are two to three orders of magnitude more potent than original allylbenzenes in terms of IC50. The inhibition of efflux pumps has been reported for allylbenzenes, and the PPh3 moiety is deemed to be responsible for preferential mitochondrial accumulation and the depolarization of mitochondrial membranes. However, due to poor solubility, the practical use of these substances has never been an option. Here, we show that this problem can be solved by using a complex formation with cyclodextrin (CD-based molecular containers) and polyanionic heparin, stabilizing the positive charge of the PPh3 cation. Such containers can solubilize both allylbenzenes and their PPh3 derivatives up to 0.4 mM concentration. Furthermore, we have observed that solubilized PPh3 derivatives indeed work as adjuvants, increasing the antitumor activity of paclitaxel against adenocarcinomic human alveolar basal epithelial cells (A549) by an order of magnitude (in terms of IC50) in addition to being quite powerful cytostatics themselves (IC50 in the range 1–10 µM). Even more importantly, CD-solubilized PPh3 derivatives show pronounced selectivity, being highly toxic for the A549 tumor cell line and minimally toxic for HEK293T non-tumor cells, red blood cells and sea urchin embryos. Indeed, in many cancers, the mitochondrial membrane is more prone to depolarization compared to normal cells, which probably explains the observed selectivity of our compounds, since PPh3 derivatives are known to act as mitochondria-targeting agents. According to the MTT test, 100 µM solution of PPh3 derivatives of allylbenzenes causes the death of up to 85% of A549 cancer cells, while for HEK293T non-cancer cells, only 15–20% of the cells died. The hemolytic index of the studied substances did not exceed 1%, and the thrombogenicity index was < 1.5%. Thus, this study outlines the experimental foundation for developing combined cytostatic medications, where effectiveness and selectivity are achieved through decreased concentration of the primary ingredient and the inclusion of adjuvants, which are safe or practically harmless substances.
... We considered 3 analytical applications of CD206 receptor-based biosensing. The first one is targeted delivery systems of the drugs to macrophages, which we considered in a series of our papers [22][23][24][33][34][35][36][37][38]. The development of the macrophage CD206 receptor-based biosensor would provide an effective testing system for optimizing of the structure of the specific ligands to alveolar macrophages for the therapy of the macrophageassociated diseases. ...
Progress in macrophage research is crucial for numerous applications in medicine, including cancer and infectious diseases. However, the existing methods to manipulate living macrophages are labor-intense and inconvenient. Here, we show that macrophage membranes can be reconstituted after storage for months at 4 °C, with their CD206 receptor selectivity and specificity being similar to those in the living cells. Then, we have developed a mannose ligand, specific to CD206, linked with PEG as an IR spectroscopy marker to detect binding with the macrophage receptor. PEG was selected due to its unique adsorption band of the C–O–C group at IR spectra, which does not overlap with other biomolecules’ spectroscopic feature. Next, competitive binding assay versus the PEG-bound ligand has enabled the selection of other higher-affinity ligands specific to CD206. Furthermore, those higher-affinity ligands were used to differentiate activated macrophages in a patient’s bronchoalveolar (BAL) or nasopharyngeal (NPL) lavage. CD206− control cells (HEK293T) showed only non-specific binding. Therefore, biochips based on reconstituted macrophage membranes as well as PEG-trimannoside as an IR spectroscopic marker can be used to develop new methods facilitating macrophage research and macrophage-focused drug discovery.
... Some natural extracts contain substances (allylmethoxybenzenes, terpenoids, etc.) [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] with a good potential as enhancers or adjuvants in combination with antibacterial drugs, including LF and MF [15,17,18,27], so that the latter can be used more efficiently and at lower doses. Also, flavonoids, terpenoids, and some polyphenols may have multiple biological effects, including antiviral, antithrombotic, anti-ischemic, anti-inflammatory, antihistamine, antioxidant [28,29], and even stimulation of mucus formation by stomach cells. ...
... Some natural extracts contain substances (allylmethoxybenzenes, terpenoids, etc.) [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] with a good potential as enhancers or adjuvants in combination with antibacterial drugs, including LF and MF [15,17,18,27], so that the latter can be used more efficiently and at lower doses. Also, flavonoids, terpenoids, and some polyphenols may have multiple biological effects, including antiviral, antithrombotic, anti-ischemic, anti-inflammatory, antihistamine, antioxidant [28,29], and even stimulation of mucus formation by stomach cells. ...
... The preparation of methyl-β-cyclodextrin (MCD) inclusion complexes was performed as earlier described [18]. ...
Bacterial infections are usually found in the stomach and the first part of the small intestine in association with various pathologies, including ulcers, inflammatory diseases, and sometimes cancer. Treatment options may include combinations of antibiotics with proton pump inhibitors and anti-inflammatory drugs. However, all of them have high systemic exposure and, hence, unfavorable side effects, whereas their exposure in stomach mucus, the predominant location of the bacteria, is limited. Chitosan and nanogels based on chitosan presumably are not absorbed from the gastrointestinal tract and are known to adhere to the mucus. Therefore, they can serve as a basis for the local delivery of antibacterial drugs, increasing their exposure at the predominant location of therapeutic targets, thus improving the risk/benefit ratio. We have used E. coli ATCC 25922 (as a screening model of pathogenic bacteria) and Lactobacilli (as a model of a normal microbiome) to study the antibacterial activity of antibacterial drugs entrapped in a chitosan nanogel. Classical antibiotics were studied in a monotherapeutic regimen as well as in combination with individual terpenoids and flavonoids as adjuvants. It has been shown that levofloxacin (LF) in combination with zephirol demonstrate synergistic effects against E. coli (cell viability decreased by about 50%) and, surprisingly, a much weaker effect against Lactobacilli. A number of other combinations of antibiotic + adjuvant were also shown to be effective. Using FTIR and UV spectroscopy, it has been confirmed that chitosan nanogels with the drug are well adsorbed on the mucosal model, providing prolonged release at the target location. Using an ABTS assay, the antioxidant properties of flavonoids and other drugs are shown, which are potentially necessary to minimize the harmful effects of toxins and radicals produced by pathogens. In vivo experiments (on sturgeon fish) showed the effective action of antibacterial formulations developed based on LF in chitosan nanogels for up to 11 days. Thus, chitosan nanogels loaded with a combination of drugs and adjuvants can be considered as a new strategy for the treatment of infectious diseases of the gastrointestinal tract.
... In order to determine the average distance (r) between the ligand (CF in drug form) and HSA Trp-214 (absorption at 280 nm) [21,24,25]) Equations (7)-(9) were applied. Formula (7): ...
... With the increase in CF's concentration, the HSA's fluorescence intensity decreased significantly (Figure 2b), and the band shifted at 7 nm towards the higher wavelengths ( Figure 2a). The effect suggests that the Trp-214 microenvironment changes to become more hydrophilic via CF's binding as hydrophilization of the fluorophore environment leads to its red shift [24,42,43]. The data is confirmed by [44,45]. ...
... Several studies have reported that albumin's secondary structure undergoes changes upon the formation of the drug-HSA complex [20,45,51,53,54]. Our research involved the use of FTIR [24,55,56] and circular dichroism spectroscopy [45,[57][58][59] to investigate the changes in the albumin's secondary structure content upon the formation of drug-form HSA complexes. We focused on the Amide I and Amide II bands in the FTIR spectra, which are sensitive to changes in the protein's secondary structure. ...
Here, we propose a drug delivery system for ciprofloxacin (CF) based on cyclodextrin (CD) polymer. We obtained a 3D matrix system with encapsulated drug molecules by crosslinking CF+CD non-covalent complexes with 1.6-hexamethylene isocyanate. The obtained polycarbamide (MAX-system) represents particles (~225 nm in diameter) that demonstrate CF’s sustained release. We investigated how the carrier affects the drug’s interaction with the biological macromolecule human serum albumin (HSA) and CF’s antibacterial properties. Compared to a binary CF–HSA system, CD decreases CF’s binding efficiency to HSA by two times, whereas CF encapsulation in a polymer matrix doubles the Ka value and prevents protein aggregation. The changes in HSA’s secondary structure indicate no alterations in the main mechanism of complex formation between CF and HSA in the presence of both CD-based carriers. CD as well as MAX systems practically do not change CF’s activity against E. coli and B. subtilis, but for MAX systems, prolonged action is realized due to CF’s sustained release. We believe that our findings are important for the further development of new, efficient drug forms.
... The molecular containers we are developing can allow us to realize their potential and achieve their synergistic effect with antibiotics: when the combined preparation of fluoroquinolone and its adjuvant is included in the delivery system, a dual mechanism of action of the adjuvants is shown: increasing the permeability of bacterial cells to the antibiotic and inhibiting the efflux of bacterial proteins, which allows for an increase in the accumulation of the drugs in bacterial cells. So, for the combination of fluoroquinolone-terpenoid, we observed a 2-3-fold increase in the effectiveness of the antibiotic (a 2-3-fold decrease in MIC) [42][43][44]. ...
... Eugenol at the highest commercial quality was purchased from Acros Organics (Geel, Belgium). Apiol with 98-99% purity was obtained by high-efficiency distillation using a pilot plant device at N.D. Zelinsky Institute of Organic Chemistry RAS (Moscow, Russia) [42]. ...
The drug resistance of pathogenic bacteria is often due efflux pumps—specific proteins that remove foreign compounds from bacterial cells. To overcome drug resistance, adjuvants are often used that can inhibit efflux pumps or other systems that ensure the resistance of bacteria to the action of antibiotics. We assumed that a new level of effectiveness with the use of an antibiotic + an adjuvant pair could be achieved by their joint delivery into the pathogen. To test this hypothesis, we constructed a series of molecular carriers based on poly-(olygo-, dendry)mers based on cyclodextrin-grafted PEI or mannan, as well as glycol chitosan, covalently bound to antibiotic, adjuvant, and the oligosaccharide ligand to the macrophage mannose receptor (CD206), which we studied earlier and showed high efficiency and selectivity of delivery of a therapeutic “cargo” to macrophages. Moxifloxacin was used as an antibiotic, and terpenoid and allylbenzene compounds were used as adjuvants, for which we previously discovered the ability to inhibit bacterial efflux pumps. We show that: (a) the resulting structures were stable in vitro for a long time (up to 10 days); (b) they were adsorbed on bacterial cells, providing a local increase in the concentration of the antibiotic and adjuvant in pathogen cells; (c) they were internalized by bacterial cells, ensuring the accumulation of both antibiotic and adjuvant inside bacterial cells; (d) the adjuvant, after entering the bacterial cell, provided inhibition of the efflux pumps; (e) due to this action of the adjuvant, combined with the targeted delivery by the carrier, the antibiotic’s half-life in rats increased by more than 2 times, the effective concentration of the drug in the blood plasma (AUC) increased up to 8–10 times; (f) a significant increase in the effectiveness of the antibacterial action against Gram+ and Gram- cells was achieved (up to 3 times). Potentially, such an approach would significantly increase the effectiveness of therapies for a number of infectious and other diseases, reduce the dosage of antibiotics, shorten the duration of treatment, and reduce the risk of developing bacterial resistance. Moreover, the use of a polymer carrier with covalently bound organic molecules of different structures will avoid problems linked to different (suboptimal) solubility and bio-distribution of the administered molecules, which would be almost inevitable when using the same compounds separately. It would be very difficult to find antibiotic/adjuvant pairs that simultaneously achieve optimal concentrations in the same target cells. In our case, terpenoids and alkylbenzenes used as adjuvants are practically insoluble as individual compounds, and their unacceptable pharmacological properties would not allow them to be used as efflux pump inhibitors.
... Moreover, except for fraction II, higher concentrations (10 mg/mL or more) of the studied fractions were needed to inhibit the growth of S. aureus, S. epidermidis, and E. coli (Table 6). Such antimicrobial actions of fractions I-III might be underlain by their content of fatty acid derivatives, alkylbenzenes, and alkyl amines (for fraction I) (Culler et al., 1979;Cowan, 1999;McGaw et al., 2002;Zlotnikov et al., 2022), flavonoids and other phenolics (for fraction II) (Xie et al., 2015;Ginovyan et al., 2017;Tak o et al., 2020), and Hammoda et al., 2018). ...
Various metabolomics approaches have greatly contributed to the study of natural products from medicinal plants. Among thousands of plant species, Narcissus pseudonarcissus L. (Amaryllidaceae) is reputed for its ornamental, industrial, and medicinal applications. This plant is also used traditionally for microbial infections, inflammations, skin complaints, and cancers. Long ago, N. pseudonarcissus has gained considerable research interest thanks to its diverse alkaloids that have been widely studied. However, the non-alkaloidal principles and different bioactivities of this plant were poorly deliberated in previous works. Therefore, this work evaluates the biological potential of N. pseudonarcissus bulbsꞌ total ethanol extract (TEE) and its derived fractions (I‒IV), along with exploring the overlooked non-alkaloidal metabolites of this amaryllid. Overall, GC‒MS-based analysis of the bulbs led to the identification of varied metabolites, e.g., long-chain alkyl amines, alkylbenzenes, long-chain hydrocarbons, fatty acid derivatives, and phenylpropanoids. Most of these phytochemicals are first characterized herein in either the genus Narcissus or the family Amaryllidaceae. Additionally, the acidic EtOAc fraction (II) exhibited the highest scavenging potential of the 2,2ꞌ-diphenyl-1-picrylhydrazyl radical and the greatest ferric reducing power, possibly due to its relatively higher contents of phenolics and flavonoids that were also estimated herein. On the other hand, the basic EtOAc fraction (III) exerted the maximum anti-proliferative actions against Caco-2 (colon) and Mcf-7 (breast) tumor cells, while all the tested fractions were inactive against HepG-2 (liver) cancer cells. Finally, different N. pseudonarcissus fractions demonstrated varied inhibitory activities against a group of pathogenic bacteria and fungi. Among them, fractions II and III were further observed as good synergists with some standard antimicrobial agents, even against some resistant microbial strains. These data could support the reported use of N. pseudonarcissus in traditional medical systems and help widen its future phytochemical and biological prospection.
... We varied the concentration of HSA and analyzed the changes in the anisotropy by Hill's linearization in n-binding site model (5) [22]: ...
Modern medical needs call for the efficient remedies against bacterial diseases including severe pulmonary infections reported as a secondary SARS-Cov-2 infection. Here, we propose imprinted drug ciprofloxacin (CF) into the polymer based on methyl-β-cyclodextrin (MCD) via template synthesis. The obtained polycarbamide nanoparticles possess CF's sustained drug release. The interaction of human serum albumin (HSA) with CF and CF-MCD carriers was conducted by FRET, FTIR, fluorescence, and circular dichroism spectroscopy. These studies uncovered that MCD decreases CF's binding efficiency by 2 times, whereas CF’s encapsulation in polymer matrix doubles the Ka value. The changes in HSA’s secondary structure indicate no alterations in the main mechanism of complex formation between CF and HSA in the presence of MCD-based carries. The drug delivery system demonstrates prolonged CF release at pH 7.4 in presence of HSA (model conditions of blood plasma). CF-MCD carriers inhibit E. coli and B. subtilis growth, but for MAX systems we observed a MIC’s increase (~2 times). We believe that our findings are important for further development of new efficient drug forms.
... We varied the concentration of CD tori in the CD polymers and analyzed the changes in the intensity of the AM emission spectra by Hill's linearization in the n-binding site model (2) [24]: ...
Respiratory infectious diseases have challenged medical communities and researchers. Ceftriaxone, meropenem and levofloxacin are widely used for bacterial infection treatment, although they possess severe side effects. To overcome this, we propose cyclodextrin (CD) and CD-based polymers as a drug delivery system for the drugs under consideration. CD polymers demonstrate higher binding affinity for levofloxacin (Ka ≈ 105 M) compared to drug–CD complexes. CDs slightly alter the drugs’ affinity for human serum albumin (HSA), whereas CD polymers increase the drugs’ binding affinity up to 100 times. The most significant effect was observed for more the hydrophilic drugs ceftriaxone and meropenem. The drug’s encapsulation in CD carriers leads to a decrease in the degree of change in the protein’s secondary structure. The drug–CD carrier–HSA complexes demonstrate satisfying antibacterial activity in vitro, and even a high binding affinity does not decrease the drug’s microbiological properties after 24 h. The proposed carriers are promising for a drug form with a prolonged drug release.
... MDR is directly caused by efflux pumps and low influx. Therefore, efflux inhibitors are promising enhancers of antitumor drugs, but many of them are toxic substances (derivatives of quinoline, naphthalene and piperazine, carbonyl cyanide), so we suggest focusing on pure substances extracted from plants (such as rosemary phytochemicals [26], Thai herbs [27], allylbenzene's derivatives and terpenoids [28,29], bicalutamide [30]). We have previously studied the process of inhibition of efflux pumps in bacterial cells of E. coli and B. subtilis by eugenol, menthol, apiol and their analogues [28,29]. ...
... Therefore, efflux inhibitors are promising enhancers of antitumor drugs, but many of them are toxic substances (derivatives of quinoline, naphthalene and piperazine, carbonyl cyanide), so we suggest focusing on pure substances extracted from plants (such as rosemary phytochemicals [26], Thai herbs [27], allylbenzene's derivatives and terpenoids [28,29], bicalutamide [30]). We have previously studied the process of inhibition of efflux pumps in bacterial cells of E. coli and B. subtilis by eugenol, menthol, apiol and their analogues [28,29]. These substances can likely be effective efflux inhibitors in tumor cells and agents acting on ion channels. ...
... For EG and its analogues, anti-inflammatory, analgesic, and antimicrobial action have been shown; moreover, EG is a synergist of antibiotics [29,[31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48]. In the aspect of antitumor activity about EG, it is known that this safe substance is comparable in strength to toxic cisplatin on some types of cells (e.g., U-937, HL-60, HepG2, 3LL Lewis, SNU-C5-IC50 is from 20 to 130 µM) [49]. ...
Oncological diseases are difficult to treat even with strong drugs due to development the multidrug resistance (MDR) of cancer cells. A strategy is proposed to increase the efficiency and selectivity of cytotoxic agents against cancer cells to engage the differences in the morphology and microenvironment of tumor and healthy cells, including the pH, membrane permeability, and ion channels. Using this approach, we managed to develop enhanced formulations of cytotoxic agents with adjuvants (which are known as efflux inhibitors and as ion channel inhibitors in tumors)—with increased permeability in A549 and a protective effect on healthy HEK293T cells. The composition of the formulation is as follows: cytotoxic agents (doxorubicin (Dox), paclitaxel (Pac), cisplatin) + adjuvants (allylbenzenes and terpenoids) in the form of inclusion complexes with βcyclodextrin. Modified cyclodextrins make it possible to obtain soluble forms of pure substances of the allylbenzene and terpenoid series and increase the solubility of cytotoxic agents. A comprehensive approach based on three methods for studying the interaction of drugs with cells is proposed: MTT test—quantitative identification of surviving cells; FTIR spectroscopy—providing information on the molecular mechanisms inaccessible to study by any other methods (including binding to DNA, surface proteins, or lipid membrane); confocal microscopy for the visualization of observed effects of Dox accumulation in cancer or healthy cells depending on the drug formulation as a direct control of the correctness of interpretation of the results obtained by the two other methods. We found that eugenol (EG) and apiol increase the intracellular concentration of cytostatic in A549 cells by 2–4 times and maintain it for a long time. However, an important aspect is the selectivity of the enhancing effect of adjuvants on tumor cells in relation to healthy ones. Therefore, the authors focused on adjuvant’s effect on the control healthy cells (HEK293T): EG and apiol demonstrate “protective” properties from cytostatic penetration by reducing intracellular concentrations by about 2–3 times. Thus, a combined formulation of cytostatic drugs has been found, showing promise in the aspects of improving the efficiency and selectivity of antitumor drugs; thereby, one of the perspective directions for overcoming MDR is suggested.
... Multiple drug resistance is directly caused by efflux pumps and low influx. In addition, adjuvants from plant extracts themselves have anticancer activity [12][13][14][15][16][17][18][19] and show synergism with cytostatics by inhibiting efflux (pumping the drug out of cells) and increasing the permeability of the membrane of cancer cells, and have prospects to show high selectivity relative to healthy due to the difference in morphology and molecular patterns of the cells of healthy and cancer. We have previously studied the process of inhibition of efflux pumps in bacterial cells of E. coli and B. subtilis by eugenol, menthol, apiol, and their analogs [19,20]. ...
... In addition, adjuvants from plant extracts themselves have anticancer activity [12][13][14][15][16][17][18][19] and show synergism with cytostatics by inhibiting efflux (pumping the drug out of cells) and increasing the permeability of the membrane of cancer cells, and have prospects to show high selectivity relative to healthy due to the difference in morphology and molecular patterns of the cells of healthy and cancer. We have previously studied the process of inhibition of efflux pumps in bacterial cells of E. coli and B. subtilis by eugenol, menthol, apiol, and their analogs [19,20]. It is logical to assume the effectiveness of these substances in tumor cells due to the similarity of structural motifs with the inhibitors used in the literature. ...
... Eugenol of the highest commercial quality was purchased from Acros Organics (Flanders, Belgium). The preparation of apiol and plant extracts was carried out in the same way as described earlier [19]. ...
The main factors that determine the low effectiveness of chemotherapy are the low target bioavailability of antitumor drugs and the efflux process. In attempts to overcome this problem, several approaches are proposed here. Firstly, the development of polymeric micellar systems based on chitosan grafted by fatty acids (different types to optimize their properties), which, on the one hand, increase the solubility and bioavailability of cytostatics and, on the other hand, effectively interact with tumor cells due to the polycationic properties of chitosan, allowing for more effective penetration of cytostatic drugs into the cells. Secondly, the use of adjuvants—synergists of cytostatics (such as eugenol) included in the same micellar formulation—that selectively enhance the accumulation and retention of cytostatics in the tumor cells. pH- and temperature-sensitive polymeric micelles developed show high entrapment efficiency for both cytostatics and eugenol (EG) > 60% and release the drug in a prolonged manner for 40 h in a weakly acidic medium corresponding to the microenvironment of tumors. In a slightly alkaline environment, the drug circulates longer (more than 60 h). The thermal sensitivity of micelles is realized due to an increase in the molecular mobility of chitosan, which undergoes a phase transition at 32–37 °C. The effect of the cytostatic drug doxorubicin (Dox) on cancerous A549 cells and model healthy cells of human embryonic renal epithelium (HEK293T) was studied by FTIR spectroscopy and fluorescence microscopy. Micellar Dox penetrates into cancer cells 2–3 times more efficiently when using EG adjuvant, which inhibits efflux, as demonstrated by a significant increase in the ratio of intra- and extracellular concentrations of the cytostatic. However, here it is worth remembering about healthy cells that they should not be damaged: according to changes in the FTIR and fluorescence spectra, the penetration of Dox into HEK293T when using micelles in combination with EG is reduced by 20–30% compared to a simple cytostatic. Thus, experimental developments of combined micellar cytostatic drugs have been proposed to increase the effectiveness of cancer treatment and overcome multiple drug resistance.
