1. Introduction
Bacterial infections
have long posed a significant public health threat due to their ability to
cause widespread disease and death. To prevent chronic wound infections,
antibacterial drugs (e.g., antibiotics and antibacterial agents) are
commonly used.[1] Despite their excellent
antibacterial activities, these substances are highly cytotoxic, and their use
is restricted by high production costs at the nanoscale and unstable chemical
properties.[2,3] This threat has been
exacerbated by the increase in antibiotic resistance emergence, which
diminishes the effectiveness of treatments and complicates the management of
common infections. The widespread resistance of clinically important pathogenic
bacteria to available antibiotics has become a global problem due to the
ever-increasing number of strains resistant to multiple antibiotics.[4,5]
Therefore, the development of novel antimicrobial substances is urgently
needed.
Biopolymers
are used in drug delivery systems due to their biocompatibility,
biodegradability, and ability to protect and release therapeutic agents in a
controlled manner. These materials can be engineered to improve the stability
and solubility of drugs, target specific tissues or cells, reduce side effects,
and enhance the overall efficacy of
treatment.[6]
Dextrin, a
polysaccharide derived from the hydrolysis of starch, is characterized by its
high safety profile, non-toxicity, biocompatibility, and biodegradability.[7]
Due to these advantageous properties, dextrin is widely employed across various
fields, including the food industry, medicine, and tissue engineering.[8]
Notably, its superior biocompatibility and wide range of properties, dextrin
and its derivatives have been extensively studied as functional ingredients for
various medical applications, particularly the prevention and treatment of
bacterial infections in wounds.[9] Additionally, good
solubility allows it to be used as a carrier for active components and
antibacterial substances.
Poly(vinyl
alcohol) (PVA) is well spread in biomedical applications due to its excellent biocompatibility,
it functions as a stabilizer and is easily degradable, rendering it a suitable
component for various medical formulations. Specifically, starch-PVA blends are
utilized in drug delivery, taking advantage of PVA's ability to improve the
stability, controlled release, and biodegradability of the drug delivery
system. This combination enhances therapeutic efficacy, while minimizing potential side effects,
making it a promising choice for the development of advanced biomedical
materials.[10-12] Iodine
exhibits potent antibacterial properties that affect various structures of
microbial cells.[13] Due to its
broad-spectrum antimicrobial activity, iodine has been extensively utilized for
decades as a disinfectant and antiseptic.[14] More importantly, highly
effective antibacterial iodine provides an alternative approach to lowering the
possibility of high drug resistance of pathogenic microorganisms caused by
antibiotic misuse.[15] The complexes formed by
iodine and carrier feature high antibacterial activity, good stability, and low
toxicity. In recent years, natural polymers have been employed for the
incorporation of iodine, leading to the development of polymer-iodine composite
materials, such as chitosan derivative-iodine microspheres and
polysaccharide-iodine composite membranes, which demonstrate remarkable
antibacterial activity.[16-19]
Classical
studies by Makhayeva et al.[20] provided a detailed
examination of the complexation mechanism between iodine and
polyvinylpyrrolidone (PVP), demonstrating that complex formation involves
charge transfer and results in a stable structure with antiseptic properties.
Telfah et al.[21] showed that the degree
of iodine incorporation and the stability of the resulting complexes vary
depending on the nature of the polymer (e.g., PEO, PVA, or
polyurethanes), offering possibilities for tuning iodine release kinetics. Pesek
et al.[22] analyzed the spectroscopic
characteristics of iodine-polymer complexes,
confirming that the complex structure influences optical properties, which can
be exploited in analytical applications. Tashiro et al.[23]
investigated the conductive properties of polymer–iodine complexes and
demonstrated their potential applicability in organic electronics.
Furthermore,
studies by Moulay et al.[24] emphasized the
suitability of polymer–iodine complexes for developing controlled-release
systems for active iodine, which is particularly relevant in the fields of
medical materials and packaging. Collectively,
these findings highlight the importance of polymer matrix selection and
complexation conditions in designing materials with tailored functional
properties.
In this
study, we propose a novel approach by combining dextrin and PVA to create an
effective iodine delivery system with enhanced antimicrobial properties and
biocompatibility, demonstrating high potential for wound management
applications. The dextrin/PVA/iodine (D/PVA/I) complex was prepared by adding
potassium iodide-iodine solutions to the polymer matrix, a semi-viscous medium
capable of stabilizing and encapsulating iodine species formed of a homogeneous
aqueous mixture of dextrin and PVA. The physicochemical properties and structures of the
complexes were determined using various techniques, such as ultraviolet-visible (UV-Vis) spectroscopy,
Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic
resonance (1H NMR) spectroscopy, X-ray diffraction (XRD), and thermogravimetric
analysis (TGA).
Furthermore,
in vitro antibacterial tests and cytotoxicity assays were used to
evaluate the antibacterial activity and cytocompatibility of the
dextrin/PVA/iodine complex, respectively. These findings lay the foundation for further
development of the dextrin/PVA/iodine complex as a biomedical material for clinical
applications.
2. Materials and methods
2.1 Materials
The reagents used
for the present work were of analytical grade, obtained from commercial
sources, and used without further purification. Potassium
iodide from Sigma-Aldrich (St. Louis, MO, USA, ³ 99%), iodine from Labpharm
(JSC "Troitsky iodine plant",
Russia, ³ 98%),
Dextrin (molecular
weight ~4000 kDa and deacetylation degree of 95%) from
Sigma-Aldrich (St. Louis, MO, USA, ³ 99%), PVA
from Sigma-Aldrich (molecular
weight ~31000 kDa St.
Louis, MO, USA, ³ 99%), nutrient agar (Himedia, India),
Tryptic Soy Agar (Himedia, India),
Muller-Hinton Broth (Himedia, India), ampicillin sodium salt (Merck, Germany),
sodium chloride >99% (Mikhailovsky
chemical reagents plant, Russia), and ethanol
(96% [Talgar Spirt’, Kazakhstan]).
2.2 Test strains
and growth conditions
The microorganisms
used in this study were selected based on their clinical significance,
multidrug resistance (MDR) profiles, and biofilm formation capacity. These
characteristics are crucial in chronic and nosocomial infections. This allowed
for a comprehensive assessment of the antimicrobial efficacy of the tested
compounds against both Gram-positive and Gram-negative bacteria. The
test strains included both reference strains obtained from the American Type
Culture Collection (ATCC, Rockville, MD, USA) and included multidrug resistant
strains of bacteria. Some of the strains used in the experiment were obtained
from their own museum collectionб were they deposited and patented as
resistant strains. Gram-positive bacteria were presented by strains Staphylococcus
aureus ATCC BAA-39, Staphylococcus aureus ATCC BAA-3359, Streptococcus
pneumoniae ATCC BAA-660 and Streptococcus pneumoniae SCAID
PHRX1-2018. ATCC BAA-196, Esсherichia coli ATCC BAA-2524, Esсherichia coli SCAID WND 1-2021
(patent #7713),
Pseudomonas aeruginosa SCAID PHRX1-2019 (patent #6286), Acinetobacter
baumannii ATCC BAA-1790, Klebsiella
pneumoniae
ATCC 700603, Klebsiella pneumoniae ATCC 2524 and clinical MDR isolate Pseudomonas
aeruginosa TA2.
Stock
cultures were stored under the low temperature conditions at −80 °C. Before the
experiments test strains were cultivated and twice passaged on Tryptic Soy Agar
and Nutrient Agar as recommended in the ATCC handling information. The cells
were incubated at 37
°C
for 18-24 h.
2.3 Test system
Cytotoxicity
of D/PVA/I-1, D/PVA/I-2 and D/PVA/I-3 was measured on two cell lines: MeT-5A
(SV40 – immortalized human mesothelial cell line, ATCC-CRL-9444, USA) and MCF-7
(human breast adenocarcinoma, ATCC-HTB-22, USA). These cell lines are
specifically produced for scientific laboratory studies. The cells proliferate
efficiently at a cell area of 1×105 cells/cm2,
reaching 100% growth within two to three days of cultivation. The culture
development was RPMI-1640 medium supplemented with 10% fetal bovine serum. The
cells were cultured under the following conditions: 37 °C, 5%
CO2 and 95% humidity. Viability after cryopreservation ≥ 90%
(trypan blue staining before culture). The source of cell cultures is ATCC. In
addition, to determine D/PVA/I-1, D/PVA/I-2 and D/PVA/I-3 substances’ toxic
effect on immune cells, human peripheral blood mononuclear cells (Human peripheral blood
mononuclear cells) were used as a test system.
2.4 Method of preparation of working solutions
2.4.1 Preparation
of iodine-potassium iodide solutions
A total of 1.16 g of potassium
iodide (KI) was
weighed in
a 100 mL glass flask and dissolved in 25 mL of purified
water. The solution was left to cool to room
temperature, 0.89 g of iodine (I2) was added, the flask was stopped, and the flask was swirled until the iodine was completely
dissolved.
2.4.2 Preparation of PVA Solution
A 100 mL glass flask was
filled with 25 mL of distilled water preheated to 40 °C, after which 0.330 g of
polyvinyl alcohol powder was added. Afterwards, the solution was thoroughly
mixed.
2.5 Preparation of the
dextrin/PVA/iodine complex
A 250 mL two-neck
round-bottom flask was filled with 50 mL of distilled water and heated using a
flask heater (LAB-FH-500 euro), while stirred. Once heated to 40 °C, a PVA
solution was poured into the flask. The
temperature was then gradually reduced to 25 °C, after which a potassium
triiodide solution was introduced into the mixture. The resulting solution was
thoroughly mixed for 10 minutes. The prepared sample was left in the flask for
12–24 hours to achieve equilibrium. The sample was dried under vacuum at a temperature of 40
оС and stored in the dark
for later use. To
obtain complexes with different iodine contents, three dextrin/PVA/iodine complexes, labelled D/PVA/I-1, D/PVA/I-2, and D/PVA/I-3, were prepared by
adjusting the molar ratio of the Dextrin, iodine and potassium iodide (D:I2:KI
=1.0:0.04:0.08, 1.0:0.02:0.04, and 0.004:0.008,
respectively).
2.6 UV-Vis spectroscopy
UV-Vis spectra of the
samples were collected using a LAMBDA-35 UV-Vis spectrophotometer (PerkinElmer, USA). The samples were dissolved in a water solution (1
mg/mL), and the solvent was used as a reference. The scanning range was
190-1100 nm.
2.7 FTIR spectroscopy
The samples were
processed via the ZnS pellet method, and their FTIR spectra were collected
using an FTIR spectrometer (Nicolet 6700
FTIR spectrophotometer, Thermo Scientific, USA).
The test
conditions
were as follows:
wavenumber range, 4000-400 cm-1; scan number, 32; and resolution, 4 cm-1.
2.8 1H NMR spectroscopy
1H NMR spectra of the
samples were collected using a superconducting Fourier NMR spectrometer JNM-ECA
500 (JEOL, Japan) operating at 500 MHz, and the solvent used was DCl/D2O (1/100,
V/V).
2.9 XRD analysis
The samples were
analyzed using an XRD diffractometer, SmartLab (Rigaku Ultima IV, Japan), under
the following conditions: Cu Kα radiation (λ = 1.54059 Å), a
one-dimensional detector (D/teX Ultra, Rigaku) with a Kβ filter, and step-scan
measurements conducted within a 2θ range of 5-90°, with a step width
(Δ2θ) of 0.1° and a scanning speed of 5°/min. Phase identification
and investigation of the crystalline structure were performed using the PDXL:
Integrated X-Ray Powder Diffraction Software and the international database
ICDD PDF-2.
2.10 Thermogravimetric
(TG) analysis
Thermal stability
analysis of the samples was performed using a TG/DSC STA 449 F1 Jupiter
(NETZSCH, Germany) under
the following conditions: nitrogen as the carrier
gas, a flow rate of 50 mL/min, a temperature range of 30-600 °C, and a heating rate of 10 °C/min.
2.11 Determination of the iodine content
The
concentration of halogens (iodine) in the complexes was measured by sodium
thiosulfate titration.[25] The
concentration of molecular iodine per 1000 g of the complex was measured by Eq. (1):
(1)
where V1
is the volume of 0.05 M sodium thiosulfate spent for complete titration; K1
is the correction
on
sodium thiosulfate concentration in the buffer, for 0.05 M solution K1
= 0.5; and m is the weight of the complex in g.
The
concentration of KI was measured by Eq. (2) using titration with
silver nitrate.[25]
(2)
where
V1 is the volume of 0.05 M sodium
thiosulfate spent for complete titration; V2 is the
volume of 0.05 M AgNO3 spent for complete titration; and K1
= K2 = 0.5, m is the weight of the complex in g.
2.12 In vitro antimicrobial
activity assay
Antimicrobial activity assay was performed using serial
broth microdilution method according to the guidelines of the Clinical and
Laboratory Standards Institute with some modifications.[26,27] The experiment was carried out in sterile 96-well polystyrene plates
(BIOLOGIX, Jinan, Shandong, China).
(1) Serial two-fold dilution preparation: All the wells of the 96-well plate were filled with 100 µL of 0.9 %
saline. Then 100 µL of samples was added into the first well in the raw of the
plate. Further serial
two-fold dilutions were performed: 100 μL of the saline+sample solution from the first well (A1) was
mixed and transferred into the next well (A2) in the raw. 100 μL of the twice diluted solution from the second well (A2) was
moved to the next well in the raw (A3) and so on, etc. until the required number of dilutions
was achieved.
All experiments were performed in triplicate.
(2) Cell suspension
preparation and inoculation:
The stock inoculum
for each test-strain was prepared by the direct colony method: an aliquot of
the test strain was taken with a bacteriological loop, transferred to a test
tube with a sterile saline, and thoroughly homogenized until a homogeneous
suspension was obtained. The density of the suspension of each studied strain
was 0.5 units (according to McFarland), which corresponds to ~1.5×108
CFU/mL. To prepare the working suspensions of bacteria, the stock inoculum was
diluted
with saline 100 times to a final concentration of ~ 1.5 × 106 CFU/mL.
Thereafter, 10 μL of prepared bacterial suspensions were added into each well of
the raw with test items. After 30 min incubation at 37 °C, 10 μL suspensions from each well were streak-plated onto nutrient
agar/tryptic soy agar medium. The minimal bactericidal concentrations of iodine-containing
compounds (MBCs) were determined as the lowest
concentrations of the antimicrobial agent inhibiting culture growth after 30
min of incubation.
2.13 In
vitro cytotoxicity assay
To determine the cytotoxic concentrations of the test
substances, the cells (MCF7 and MeT-5A) were seeded in a 96-well plate at a
concentration of 3×104 cells/unit and left for 24 hours in a CO2
incubator (except for mononuclear cells, they were seeded in wells at a
concentration of 1×105 cells/unit). After 24 hours, the medium was
replaced with a fresh medium containing the test substances of the following
concentrations: 5.0, 2.5, 1.25, 0.625, 0.312, 0.156, 0.078, 0.039 and 0.019
mg/ml. Each concentration rate was used thrice. RPMI-1640 medium was used as a
diluent. The duration of exposure of the cells to the test substances was 48
hours in a СО2 incubator.
The negative control consisted of cells without the addition of the test
substances.
The arithmetic mean value of optical density (OD)
() for the concentration of each test substance was calculated using Eq. (3).
(3)
where yi is the result of
measuring the OD for each object in the group; n is the
number of objects
in the group.
The
percentage of viability for each replicate of each concentration of the test
substance was calculated using Eq. (4).
(4)
where Yi is the result of OD measurement
for each group; 
NC is the arithmetic mean value of OD () for the negative control.
The standard deviation and percentage of viable cells for
each concentration of the test substance were calculated using Eq. (5).
(5)
2.14
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay
Cytotoxicity analysis was performed
using the MTT method. This method for determining cell viability is based on
the ability of living cells to convert soluble yellow
3-(4,5-dimethylthiazol-2-yl)-2,5-tetrazolium bromide into insoluble purple-blue
intracellular formazan crystals. Nonviable dead cells do not have this ability.
Four hours before the end of the studied drugs action, a 5 mg/ml MTT solution
was added to the cultured cells. The cells were then cultured for the remaining
4 hours in a CO2 incubator at 37 °C, 5% CO2 and 95%
humidity. After removing the culture medium, the formazan crystals were dissolved
in 100 μl DMSO for 10 min. The amount of formazan crystals increases in
direct proportion to the number of viable cells. The OD of dissolved formazan
was measured using a Sunrise RC.4 microplate reader at 540/620 nm.[28]
3.
Results and discussion
3.1 Physicochemical properties of the dextrin/PVA/iodine complexes
Dextrin/PVA/iodine complexes are solutions
of a complex iodine compound with polydentate ligands, represented by
carbohydrate and polymer associates. The active substance of the sample is an
iodine-polymer complex, which serves as a matrix from which the active molecule
iodine is gradually released. The colour, percentage yield and melting points (M.P) or
temperature of decomposition (d) of the dextrin/PVA/iodine complexes are presented in Table 1.
The complex was dark brown in color. The solubility of the complexes in water was determined by the Flask method (to determine
values above 0.01 g/L) according to the OECD guidelines for the testing of chemicals (water solubility).
Table 1: Physicochemical properties of the dextrin/PVA/iodine complexes.
|
No
|
Name of indicators
|
Results
|
|
D/PVA/I-1
|
D/PVA/I-2
|
D/PVA/I-3
|
|
1
|
Empirical formula
|
[C8H14O6·I3]n
|
|
2
|
Molecular weight, g/mol
|
587 g/mol
|
|
3
|
pH
|
4.76
|
4.71
|
4.96
|
|
4
|
Solubility in water, g/100 mL
|
20 g (at 25 °C)
|
20 g (at 25 °C)
|
20 g (at 25 °C)
|
|
5
|
Melting temperature (°C)
|
172 (143-145)
|
182 (128-134)
|
194 (106-110)
|
|
6
|
Colour
|
Dark brown
|
Dark brown
|
Dark brown
|
|
7
|
Iodine content, (%)
|
4.27
|
2.49
|
0.79
|
|
8
|
Viscosity, mm2/s
|
12.06
|
4.50
|
1.14
|
|
9
|
Density, g/cm3
|
1.065
|
1.028
|
0.993
|
|
10
|
Yield (%)
|
95
|
95
|
96
|
3.2 UV-Vis spectral analysis
The UV-Vis spectra of dextrin,
PVA, and dextrin/PVA/iodine complexes are shown in Fig.
1. In the scanning range, the absorption peak of dextrin was located at
~278 nm, which is attributed to the n–π transition of heteroatoms (such as
oxygen) in the dextrin molecule. The n–π transition requires relatively
low energy, resulting in a weak absorption band at ~278–279 nm, which is
consistent with the findings of Zhanguang Chen et al.[29] In the UV-Vis spectrum of PVA, three absorption
peaks were observed at 207 nm, 279 nm, and 327 nm. These bands are assigned to
n→π and π→π transitions, respectively. The
n→π transition is likely due to the C=O groups, while the
π→π transitions can arise from unsaturated bonds, such as C=C
or conjugated C=O, possibly originating from residual acetate or oxidation
byproducts at the terminal or side groups of PVA chains. In the spectrum of the
dextrin/PVA/iodine complex, three new absorption peaks appeared at 199 nm, 287
nm, and 351 nm. These peaks are attributed to the presence of molecular iodine
(I2) and triiodide ions (
), which are known to exhibit strong charge-transfer
transitions in this region. These
findings are consistent with the results reported by Sai et al.,[30]
such absorption features are characteristic of complexes and support the successful formation of a
charge-transfer complex between iodine and the polymer matrix.
Fig. 1: UV-Vis spectra of Dextrin, PVA and D/PVA/I
complex.
3.3 FTIR spectral analysis
The largest mass
fraction in the dextrin/PVA/iodine complex is occupied by dextrin. In this
regard, to clarify the interaction of the complex components, it is relevant to
trace the changes occurring in the spectrum of dextrin in the final complex. Fig. 2
shows the IR spectra of dextrin, PVA, and dextrin/PVA/iodine. As shown in Fig. 2 (b),
the bands at 3312 and 2925 cm-1 of free dextrin are attributed to
the O-H stretching vibration and C-H stretching of the -CH2 group,
respectively. The peak at 1646 cm-1 is attributed to the wide
intense band at С=С.[31-35] Moreover, the peaks at
1417 and 1336 cm-1 are related to the bending vibrations of the CH3
and CH2 groups,[31,32,36,37] and the peaks at 1146,
1076 and 994 cm-1 are related to the stretching vibrations of the
C-O-C glycoside bond and the stretching vibrations of the C-O bonds.[31-34]
The peak at 928 cm-1 is related to ring bond vibrations, and the
peaks at 857 and 761 cm-1 are related to bending vibrations outside
the plane of CH. [31,32,35]
In
the spectrum of PVA, the large bands observed between 3332 cm-1 are linked
to the stretching of O–H from intermolecular and intermolecular hydrogen bonds. The
vibrational band observed at 2916 cm-1 refers to the stretching of C–H bonds from alkyl
groups. The
vibration bands at 1732, 1430, 1374, 1243, 1086 and 837 cm-1
corresponded to the stretching vibration, C=O carbonyl stretch, C–H bending
vibration of CH2, C–H deformation vibration, symmetrical stretching
vibrations of the ring, C–O stretching of acetyl groups and C–C stretching vibration, respectively.[38-40]
Compared
to those of
dextrin,
the spectra of the
dextrin/PVA/I
samples show that the most intense bands in both spectra correspond to C-O
bonds. However, there is a noticeable shift in the wavenumbers. For dextrin, the wavenumber was 994 cm-1,
while in the complex, it shifted to 1016 cm-1.
Shifts are also observed in other less intense bands. After the most intense
peak in the dextrin spectrum, bands with wavenumbers of 925, 857, and 761 cm-1
are present. In the spectrum
of the complex,
the corresponding bands shifted to 923, 850, and 767 cm-1.
These results demonstrate the complexation of iodine with dextrin.
Fig. 2: IR spectra of dextrin (a), PVA (b), and
dextrin/PVA/iodine
(c)
3.4 1H
NMR characterization
1H NMR spectroscopy has proven to be an invaluable method for
investigating the subtle structural differences in polymeric materials. The 1H
NMR spectra of Dextrin, PVA and Dextrin/PVA were shown in Fig. S1. In the 1H NMR
spectrum of dextrin, the anomeric proton of the glucose unit (H1) appears
downfield at 5.244 ppm. Protons attached to carbons C2–C6 of the glucose units
are observed in the range of 3.1–3.7 ppm, with specific signals at 3.102,
3.253, 3.472, 3.610, and 3.668 ppm. A methylene group (CH2) associated
with the branching point is detected at 3.796 ppm. Additionally, a weak signal
from the hydroxyl group (OH) is observed at 5.067 ppm. These findings align
with previously reported data.[41] the 1H
NMR spectrum of polyvinyl alcohol (PVA), several characteristic peaks are
observed. The protons on the carbon attached to the hydroxyl group (–CH2OH)
appear in the range of 3.2-4.0 ppm (3.555, 3.699, and 3.869 ppm). The proton in
the methylene group attached to the main chain carbon (–CH2–CH–) is
observed between 1.4-2.0 ppm (1.429, 1.475, 1.540, 1.756, and 1.938 ppm), with
slight variations due to the polymer's structure and molecular weight. A
methylene proton associated with the carbon at C3 (C–CH2)
is detected at 3.183 ppm. Incomplete hydrolysis would show protons near the
acetate group in the 2.1-2.4 ppm range, but in this sample, complete hydrolysis
occurred, and no residual acetate groups are visible. Hydroxyl protons
(−OH) are seen as a broad signal at 5.087 ppm. These results confirm the
structure of PVA and its complete hydrolysis.
Comparison of the NMR spectra of dextrin, PVA, and their mixture
with iodine and potassium iodide reveals distinct changes in chemical shifts
and signal intensities, particularly in the 3.5-5.5 ppm region, indicating
interactions between the components. In the spectrum of the mixture, signal
broadening and shifts are observed, suggesting alterations in electron density
within hydroxyl and ether groups, likely due to hydrogen bonding and
complexation with iodine. These spectral changes confirm that iodine and
potassium iodide interact with dextrin and PVA, forming a stable polymer-iodine
complex, which may result from both physical adsorption and chemical bonding
through donor-acceptor interactions.
3.5 XRD analysis
The crystal structure of dextrin, PVA and the structural changes in
its complexes with iodine were probed using an X-ray diffractometer, and the
XRD patterns were presented in Fig. 3.
In the XRD
patterns of dextrin, a characteristic broad hump was observed in the range of 2θ = 15-30°, indicating an amorphous
structure. The typical diffraction peak associated with the (020)
crystallographic plane appeared as a broad feature, suggesting that dextrin
exists in an amorphous state. These findings are consistent with previously
reported data.[42,43] The XRD pattern of PVA reveals two
distinct peaks at 20.5° and 42.6°, which are indicative of the semi-crystalline nature of the PVA
membrane.[44] The semi-crystalline structure of PVA is
stabilized by both intramolecular and intermolecular hydrogen bonding.[45] In the D/PVA/I sample, the peak in the 19–20°
2θ region becomes broader and less
pronounced, indicating a reduction in crystallinity due to the interaction of
the components. This confirms the formation of a polymer-iodine complex, in
which iodine destabilizes the crystalline regions of PVA, promoting greater
structural amorphization.
Fig. 3: XRD patterns of
Dextrin, PVA, and D/PVA/I complexes.
3.6 TG
analysis
According to the TG curves (Fig. 4a), the thermal decomposition behavior of the
samples can be roughly divided into three stages at a constant heating rate of
10 °C/min. During the first stage, mass loss
was observed between 28 and 150 °C for
D/PVA/I-1 (5.9%), between 28 and 169 °C
for D/PVA/I-2 (9.4%), and between 28 and 175 °C for D/PVA/I-3 (8.3%). This may be attributed to
moisture loss, indicating that the complexes were not entirely anhydrous. The
second stage, between 150 and 280 °C,
corresponds to the glass transition of the samples, with mass losses of 22.6%,
28.8%, and 31.8% for the three complexes, respectively. In the third stage (218–600 °C), the TG curves sharply decreased, which was
attributed to the cleavage of substituents and the depolymerisation of
polysaccharide chains. In this stage, the mass losses were 24.46% for
D/PVA/I-1, 22.49% for D/PVA/I-2, and 18.72% for D/PVA/I-3. The residual mass
percentage recorded for D/PVA/I was 40.0%.
According to the
differential thermal gravimetric (DTG) curves (Fig. 4b),
the peak temperature indicates the rate of fastest mass loss for the sample at
that temperature. The peak temperatures for mass loss associated with dextrin
dehydration were 74 and 85 °C,
suggesting that dextrin has a high affinity for water and requires more energy
to vaporize water molecules. The onset decomposition temperature of dextrin was
306 °C, while those of D/PVA-I-1, D/PVA-I-2, and
D/PVA-I-3 were 160, 171, and 187 °C,
respectively. Furthermore, the peak decomposition temperature of dextrin was
314 °C, and those of D/PVA-I-1, D/PVA-I-2, and
D/PVA-I-3 were 172, 182, and 194 °C,
respectively. These results suggest that the chemical modification of dextrin
and its complexation with iodine led to a decrease in thermal stability due to
the local amorphization of the crystalline structure of dextrin. To ensure the
stability of the complexes, all technical operations should be carried out at
temperatures below 160 °C.
Fig.
4: (a) TG
analysis curve and
(b) DSC analysis
curve of D/PVA/I
complexes.
Based
on the results of UV-Vis spectroscopy, FTIR spectroscopy, ¹H NMR spectroscopy, XRD
analysis, and thermogravimetric analysis, the structural formula of the dextrin/PVA/iodine complex has been proposed, as illustrated in Fig. 5.
Fig.
5: The
structure of Dextrin/PVA/I complex.
3.7
Antibacterial effect
The emergence of MDR
pathogens poses a significant challenge to public health, leading to limited
therapeutic options and increased mortality rates. In this context, our D/PVA/I
complexes offer a promising alternative. Iodine-containing polymeric systems
have demonstrated efficacy against MDR strains, including S. aureus and E.
coli. Notably, the iodine-containing nano-micelle FS-1 has been shown to
revert antibiotic resistance in S. aureus by inducing oxidative stress
and destabilizing resistance-conferring genomic elements.[46] Furthermore,
iodine-based materials have been effective in managing biofilm-associated
infections, which are often resistant to conventional antibiotics. The D/PVA/I
complexes, with their controlled iodine release, may provide sustained
antimicrobial activity, addressing both planktonic and biofilm-forming
bacterial populations.[47]
The
incorporation of iodine into polymer matrices not only enhances antimicrobial
efficacy but also offers stability and controlled release, making these
complexes suitable for various clinical applications, including wound dressings
and implant coatings. The antibacterial activity of samples
D/PVA/I-1, D/PVA/I-2 and D/PVA/I-3 were tested by the two-fold
dillution test against Gram-positive and Gram-negative bacteria. The test
results are illustrated in Table 2.
Table 2: MBC values of
samples against test-strains.
|
Strains
|
D/PVA/I-1
|
D/PVA/I-2
|
D/PVA/I-3
|
|
MBC values, μg/mL
(I2 Content Concentration per Total Concentration of
the Substance)
|
|
S. aureus ATCC BAA-39
|
0.33
|
0.68
|
10.68
|
|
S. aureus ATCC BAA-33591
|
0.33
|
0.68
|
10.68
|
|
E. coli ATCC 196
|
0.68
|
1.34
|
21.60
|
|
E. coli ATCC 2523
|
0.68
|
1.34
|
21.60
|
|
E. coli SCAID URN 1-2020
|
0.68
|
1.34
|
21.60
|
|
K. pneumoniae ATCC 700603
|
0.68
|
2.67
|
21.60
|
|
K. pneumoniae ATCC 2524
|
0.68
|
2.67
|
21.60
|
|
P. aeruginosa ТА2
|
0.68
|
1.34
|
21.60
|
|
P. aeruginosa WND 1-2022
|
0.68
|
0.68
|
21.60
|
|
A. baumannii ATCC 1790
|
0.33
|
0.33
|
10.68
|
|
S. pneumoniae ATCC 660
|
0.33
|
0.33
|
10.68
|
|
S. pneumoniae SCAID PHRX 1-2018
|
0.68
|
0.68
|
10.68
|
The
provided table presents the mminimum bactericidal concentration (MBC) values,
expressed in micrograms per milliliter (μg/mL), for a series of bacterial
strains subjected to different formulations, designated as D/PVA/I-1,
D/PVA/I-2, and D/PVA/I-3. These formulations represent variations in the iodine
(I2) content relative to the total concentration of the substance,
with each formulation exhibiting distinct antibacterial properties based on its
iodine concentration. The MBC value is defined as the lowest concentration of
the substance required to completely inhibit bacterial growth, making it an
essential metric for evaluating antimicrobial efficacy.
Table 2
shows that the minimum bactericidal concentrations (MBCs) of the D/PVA/I
complexes increase significantly from D/PVA/I-1 to D/PVA/I-3 across all tested
bacterial strains. D/PVA/I-1 exhibits the highest antimicrobial activity
(lowest MBC values), while D/PVA/I-3 demonstrates markedly reduced efficacy,
particularly against Gram-negative bacteria such as E. coli, K. pneumoniae,
and P. aeruginosa (MBCs reaching up to 21.6 μg/mL).
This
trend is closely linked to the structural properties and iodine availability
within the complexes. D/PVA/I-1 likely contains iodine in a more labile or
diffusible form, perhaps due to weaker interactions between iodine and the
polymer matrix, facilitating greater bioavailability. In contrast, D/PVA/I-3
may possess a denser or more crosslinked PVA structure, which could sequester
iodine more tightly, reducing its release and thereby diminishing antimicrobial
potency.
The
disparity in activity between Gram-positive and Gram-negative strains further
supports this, as the outer membrane of Gram-negative bacteria provides an
additional diffusion barrier, amplifying the importance of iodine release
kinetics. Notably, S. aureus and S. pneumoniae remain susceptible even to
D/PVA/I-2, while Gram-negative strains show a sharper decline in sensitivity.
For
Staphylococcus aureus strains (ATCC BAA-39 and ATCC BAA-33591), both
D/PVA/I-1 and D/PVA/I-2 exhibit high MBC values (0.33 μg/mL and 0.68
μg/mL, respectively),
demonstrating strong antibacterial activity. However, the formulation with
lower iodine concentration (D/PVA/I-3) shows a significantly lower MBC (10.68
μg/ml). This suggests that higher iodine concentrations are more effective
against Staphylococcus aureus, which is consistent with the literature
data that emphasizes iodine’s ability to disrupt cell wall synthesis and
protein functions in Gram-positive bacteria.[48] The observed
decrease in bactericidal activity with the lower iodine concentration in
D/PVA/I-3 may indicate that a critical threshold of iodine is required to
effectively combat Staphylococcus aureus.
Similarly,
for Escherichia coli (ATCC 196, ATCC 2523 and SCAID URN 1-2020), the MBC values
increase with decreasing iodine concentrations. The MBC for D/PVA/I-1 is 0.68
μg/mL, doubling for
D/PVA/I-2 (1.34 μg/mL), and
dramatically escalating to 21.6 μg/mL for D/PVA/I-3. This trend suggests that
iodine concentration plays a crucial role in enhancing the bactericidal
efficacy against Gram-negative bacteria such as E. coli. This finding aligns
with existing studies that indicate iodine-based formulations are highly
effective against E. coli, likely due to iodine’s oxidative effects on the cell
membrane and bacterial DNA.[49]
For
Klebsiella pneumoniae strains, the MBC values follow a similar trend,
increasing from 0.68 μg/mL (D/PVA/I-1) to 2.67 μg/mL (D/PVA/I-2), and
reaching 21.6 μg/mL for D/PVA/I-3.
This suggests that while the higher iodine concentrations provide better
bactericidal performance, the lower iodine concentration in D/PVA/I-3 is
significantly less effective against this pathogen. These results are
consistent with literature reports that Klebsiella pneumoniae can be
more resistant to lower concentrations of iodine due to its thicker outer
membrane, which may reduce the penetration of iodine.[50]
Remarkably,
the MBC values for Pseudomonas aeruginosa (TA2 and WND 1-2022 strains)
remain relatively stable across D/PVA/I-1 and D/PVA/I-2, with values around
0.68 μg/mL, respectively.
However, there is a significant decrease in MBC for D/PVA/I-3 (21.6 μg/mL). This suggests a
possible tolerance or resistance mechanism in Pseudomonas aeruginosa at
higher iodine concentrations, which has been previously reported in the
literature.[51]
The resilience of P. aeruginosa to iodine may be attributed to its
robust efflux pumps or the production of biofilms that limit iodine
penetration.[52]
For
Acinetobacter baumannii and Streptococcus pneumoniae (ATCC 660
and SCAID PHRX 1-2018), the MBC for D/PVA/I-1 and D/PVA/I-2 is relatively high
(0.33 μg/mL), and it
decreases to 10.68 μg/mL for D/PVA/I-3. This finding is in line with the literature
suggesting that Streptococcus pneumoniae is generally sensitive to iodine-based
compounds.[53]
The
observed trends in the MBC values of your D/PVA/I complexes align with findings
from other studies on iodine-containing polymeric systems. For instance,
research on PVP-iodine complexes has demonstrated their efficacy against both
Gram-positive and Gram-negative bacteria, with the degree of crosslinking
influencing the release rate and, consequently, the antimicrobial activity.
Similarly, studies on controlled-release iodine foam dressings have highlighted
the importance of iodine availability in combating biofilm formation and
bacterial growth.[54-56] These studies suggest that the structural
characteristics of iodine-polymer complexes, such as crosslinking density and
iodine release kinetics, play a crucial role in determining their antimicrobial
efficacy. The higher MBC values observed in your D/PVA/I-3 complex may be
attributed to a more tightly bound iodine structure, leading to slower release
rates and reduced antibacterial activity.
The
antimicrobial action of iodine is primarily due to its ability to penetrate
bacterial cell walls and disrupt cellular processes. In polymer-iodine
complexes, the release of iodine is influenced by the polymer's structure and
the nature of the iodine-polymer interaction. For example, in PVP-iodine
complexes, iodine is coordinated with the nitrogen atoms of the pyrrolidone
rings, and the release rate can be modulated by adjusting the degree of
crosslinking.[56]
In
the D/PVA/I complexes, variations in iodine content and polymer crosslinking
likely affect the release dynamics, with D/PVA/I-1 exhibiting the most rapid
iodine release and, consequently, the highest antimicrobial activity. The
slower release in D/PVA/I-3 may result in suboptimal iodine concentrations at
the bacterial cell surface, leading to diminished efficacy.
3.8.
Evaluation of cytocompatibility
The cytotoxicity of
D/PVA/I-1, D/PVA/I-2 and D/PVA/I-3 substances was determined by the viability
of MCF7, MeT-5A and human PBMC cells using the MTT method. The cytotoxicity of
D/PVA/I-1, D/PVA/I-2, and D/PVA/I-3 was determined by the viability of MCF7,
MeT-5A, and PBMC human cells using the MTT assay. The results of the studies of
D/PVA/I-1 showed moderate toxicity to the MCF7 tumor line at a concentration of
5 mg/mL (62.4% viable cells) and to PBMC at concentrations of 5 and 2.5 mg/mL
(52.0% and 56.6% viable cells, respectively), while a dose-dependent effect was
observed in PBMC. In the case of the normal MeT-5A cell line, D/PVA/I-1 at
concentrations of 5.0 mg/mL and 2.5 mg/mL resulted in a pronounced toxic effect
on the cells (13.8% and 23.0% viable cells, respectively), as shown in Fig. 6.
Studies
of D/PVA/I-2 showed that moderate toxicity was observed with respect to PBMC
(61.5% viable cells) when exposed to a concentration of 5.0 mg/mL, and
pronounced toxicity was observed with respect to the normal MeT-5A cell line
(47.0% viable cells). No pronounced toxic effect was shown with respect to the
MCF7 tumor line when exposed to D/PVA/I-2, as shown in Fig.
7. Substance D/PVA/I-3 showed no toxic effect for the studied
concentrations on the MCF7 tumor line, the normal MeT-5A cell line, and PBMC.
Fig. 6: Cell viability after 48-hour
exposure to D/PVA/I-1.
Fig. 7: Cell viability
after 48-hour exposure to D/PVA/I-2.
In a
comparative analysis of the CAC50 of substances D/PVA/I-1, D/PVA/I-2 and
D/PVA/I-3 using Tukey's multiple comparison test, no statistically significant
differences were found between the groups (Fig. 8).
Although
the results suggest a relatively low cytotoxic effect of D/PVA/I-1 and
D/PVA/I-2 on the normal MeT-5A cell line and PBMCs, this effect may be
influenced by higher than MCF7 tumor line susceptibility.
Fig. 8: Comparative analysis of the effect
of the studied substances on tumor and normal cell lines and PBMC (CAC50, mean
± SEM; n=4).
4.
Conclusion
In this study,
dextrin/PVA/iodine (D/PVA/I) complexes were successfully synthesized and
structurally characterized using a combination of UV-Vis, FTIR, ¹H NMR, XRD,
and TG analysis. The antimicrobial performance of these complexes was shown to
be influenced by iodine concentration, with D/PVA/I-1 and D/PVA/I-2, which
contain higher iodine levels, demonstrating greater efficacy against both
Gram-positive and Gram-negative bacteria. However, the relationship between
iodine content and bactericidal activity is not strictly linear and appears to
vary depending on the bacterial strain. For instance, Pseudomonas aeruginosa
exhibited tolerance to high iodine levels, suggesting the presence of
resistance mechanisms that warrant further investigation.
The study
also assessed the cytotoxic effects of the complexes. While D/PVA/I-1 and
D/PVA/I-2 showed moderate cytotoxicity toward normal MeT-5A cells at high
concentrations, their toxicity toward peripheral blood mononuclear cells
(PBMCs) was relatively low, indicating a potential safety margin for biomedical
applications. These findings underscore the importance of dose optimization to
balance antimicrobial efficacy with biocompatibility. From a practical
standpoint, the D/PVA/I complexes-particularly the higher iodine
formulations-show promise for clinical and industrial applications, such as in
wound care, antiseptic coatings, and disinfectant formulations. Nevertheless,
further preclinical and clinical studies are required to fully assess their
long-term safety, stability, and effectiveness in real-world conditions.
Additionally, future works should focus on tailoring the formulations to
overcome bacterial resistance and to minimize potential cytotoxic effects.
Acknowledgements
The authors would like to thank the control and analytical
laboratory of SCAID for assisting in preparing the materials for the article. This
research has been/was/is funded by the Committee of Science of the Ministry of
Science and Higher Education of the Republic of Kazakhstan (Grant No.
BR24992760).
Conflict of Interest
There is no conflict of interest.
Supporting Information
Applicable.
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