G. PETRIASHVILI et al.: LIGHT-STIMULATED LOWERING OF GLUCOSE CONCENTRATION ...
119–125
LIGHT-STIMULATED LOWERING OF GLUCOSE
CONCENTRATION IN A DEXTROSE SOLUTION MEDIATED BY
MEROCYANINE MOLECULES
S SVETLOBO STIMULIRANO ZMANJ[ANJE VSEBNOSTI
GLUKOZE V DEKSTROZNI RAZTOPINI S POMO^JO
MEROSIANINSKIH MOLEKUL
Gia Petriashvili,
1
Ketevan Chubinidze,
1*
Tamara Tatrishvili,
2
Elene Kalandia,
1
Ana Petriashvili,
1
Mariam Chubinidze
3
1
Institute of Cybernetics of Georgian Technical University, Z. Anjaparidze 5, 0186 Tbilisi, Georgia
2
Tbilisi State University, Department of Macromolecular Chemistry, I. Chavchavadze Ave.1, 0179 Tbilisi, Georgia
3
Jo Ann University Hospital, Ljubljana 35, 0159 Tbilisi, Georgia
Prejem rokopisa – received: 2022-10-03; sprejem za objavo – accepted for publication: 2023-01-23
doi:10.17222/mit.2022.639
Diabetes mellitus is a chronic metabolic disease characterized by elevated blood glucose levels and has become a global chal-
lenge. Currently, the widespread and regular treatment of diabetes mellitus involves the administration of insulin. However, in-
sulin is no longer considered the first choice for type 2 diabetes, and an expanding range of new treatment modalities are emerg-
ing as noninsulin-based medications that are promising alternatives to regulate blood glucose levels. In this regard, controlling
the glucose level in blood by external stimuli, such as light, offers a new route to governing the blood glucose concentration
with the required dose and at the appropriate time. Here, we report on a light-stimulated glucose-lowering method based on
spiropyran-merocyanine photoisomerization. We show that upon exposure to violet light (405 nm), the closed isoform of
spiropyran molecules inside liquid crystal microspheres transforms into the open merocyanine isoform, which in turn stimulates
merocyanine to translocate through the interface of the liquid crystal/dextrose emulsion. Merocyanine readily interacts with glu-
cose molecules and causes a lowering of the emulsion’s total glucose concentration by 20 %.
Keywords: diabetes mellitus, dextrose, merocyanine, light-stimulated
Sladkorna bolezen je kroni~na metaboli~na bolezen za katero je zna~ilna visoka vsebnost glukoze v ~love{ki krvi in zaradi svoje
raz{irjenosti po svetu postaja globalni izziv. Trenutno obstaja vrsta zakonitih na~inov zdravljenja sladkornih bolezni, ki
vklju~ujejo uporabo inzulina. Zdravljenje z inzulinom se ne upo{teva ve~ kot prva izbira za zdravljenje diabetesa tipa 2. Uvaja
se nova raz{irjena vrsta zdravil, ki ne temeljijo na doziranju inzulina. To so obetajo~e alternativne re{itve za reguliranje ravni
glukoze v krvi. Pri tem se lahko kontrolira raven glukoze v krvi z zunanjo stimulacijo, kot je na primer svetloba, ki ponuja nov
na~in uravnavanja koncentracije glukoze v krvi z zahtevano dozo in ob pravem ~asu. Opisana je metoda, ki temelji na svetlobno
stimuliranem zmanj{evanju glukoze s spiropiran-merosianinsko fotoizomerizacijo. Izkazalo se je, da se zaradi izpostavljenosti
vijoli~ni svetlobi z valovno dol`ino 405 nm, zaprte izoformne spiropiranske molekule znotraj teko~e kristalne mikrosfere
pretvorijo v odprto merosianinsko izoformo, ki posledi~no stimulra premestitev merosianina preko fazne meje teko~i
kristal-dekstrozna emulzija. Merosianin tako brez te`av reagira z molekulami glukoze in povzro~i zmanj{anje celotne
emulzijske glukoze za petino.
Klju~ne besede: sladkorna bolezen, dekstroza, merosianin, svetlobna stimulacija.
1 INTRODUCTION
Diabetes mellitus, more simply called diabetes is a
chronic, metabolic disease causing the majority of heart
attacks, strokes, kidney failures, blindness and lower
limb amputation. Nowadays, the number of people suf-
fering from diabetes and its complications is increasing,
in part due to the current worldwide lifestyle: sedentary
lifestyle, high-fat diet, obesity and longer life span. Dia-
betes has become a global health problem since it is the
most common clinical disorder, affecting nearly 10 % of
the world’s population and constantly increasing day by
day. The World Health Organization (WHO) reported
that about 1.1 million people die of diabetic complica-
tions annually, and the death rate is expected to increase
up to 50 % in 2030.
1
The glucose absorbed from the gas-
trointestinal tract is distributed to tissues via systemic
circulation under the control of insulin, a hormone,
which causes sugar to move from the bloodstream to the
body’s cells and is stored and utilized as an energy
source. People suffering from type 2 diabetes are resis-
tant to insulin, which keeps a person’s blood sugar at
high levels.
2
Although insulin represents a lifesaving
therapeutic aid for people suffering from diabetes, at
present, it is no longer considered the first choice for
type 2 diabetes, and an expanding range of new thera-
peutic possibilities is emerging. While these may lack
the potency of insulin, at a minimum, they allow a major
reduction in the intensity of insulin use. Therefore, the
Materiali in tehnologije / Materials and technology 57 (2023) 2, 119–125 119
UDK 544.526:542.952.16:616.379-008.64 ISSN 1580-2949
Original scientific article/Izvirni znanstveni ~lanek MTAEC9, 57(2)119(2023)
*Corresponding author's e-mail:
chubinidzeketino@yahoo.com (Ketevan Chubinidze)

search for new glucose-lowering drugs with minimal or
no side effects is undoubtedly an active challenging area
for research and development worldwide.
3
Until now, multiple novel mechanisms potentially
mediating a reduction in plasma glucose concentrations
are being explored, and various antidiabetic drugs have
been used to improve the pathological condition in pa-
tients with diabetes. Sulfonylurea drugs, glinide, dipep-
tidyl-peptidase 4 inhibitors, thiazolidinediones, acarbose,
metformin, and sodium-glucose cotransporter 2 (SGLT2)
inhibitors are used as oral medications for the diabetes
treatment. Recently, Japan and South Korea have devel-
oped novel glucose-lowering drugs, such as anagliptin,
gemigliptin, evogliptin, teneligliptin, telegliptin, gaso-
gliptin, and retagliptin.
4–7
Some medications reduce the
glucose concentration produced by the liver and slow
down the conversion of carbohydrates into sugar. Other
medications improve the way insulin works in the body
by allowing more glucose to enter into muscles, fat and
liver, lowering the blood glucose by delaying the break-
down of carbohydrates and reducing the glucose absorp-
tion in the small intestine. However, in any case, it is of
great importance to control the intake of antidiabetic
drugs to prevent drug overdose. Controlled drug delivery
systems have emerged as an alternative to the conven-
tional sort to improve the bioavailability and extent of
the drug release, and to maintain drug plasma levels
within the therapeutic window with minimal side effects.
Among the controlled drug-releasing strategy, the stim-
uli-responsive method appears as a promising approach
to governing and targeting the temporal and spatial pre-
sentation of drugs in the body. When these stimuli-re-
sponsive drug delivery systems are administered, the
drug release is activated and then modulated through
some action or external input and facilitated by the en-
ergy supplied externally. The stimuli-responsive systems
can control drug biodistribution in response to specific
stimuli, either exogenous (variations in temperature,
magnetic field, ultrasound intensity, light or electric
pulses) or endogenous (changes in pH, enzyme concen-
tration or redox gradients).
8,9
Light-activated and light-controlled drug delivery
systems offer distinct advantages over other stimuli be-
cause the light is a fascinating and green stimulus with a
micron- or submicron-sized focusing area with controlla-
ble wavelength and energy, non-invasive and non-de-
structive nature, precisely controlled direction and avail-
ability that can release a drug at a desired time and place,
so it only targets cells and not the surrounding healthy
tissues.
10
One of the unique examples of light-controlled
molecular switches is the spiropyran (SP), whose
closed-ring, hydrophobic isomer transforms into a highly
polar, open-ring merocyanine (MC) isoform upon expo-
sure to UV light, whereas the reverse reaction can be in-
duced by visible light or heat. SPs are the most promi-
nent example of light-activated molecules that are far
more than just simple photoswitches. The range of stim-
uli able to induce its reversible isomerization is truly im-
pressive and includes different solvents, metal ions, ac-
ids, bases, temperature, redox potential and mechanical
force.
11,12
In this regard, using the photoswitches like
SPs, which will control the amount of glucose in the
blood upon exposure to light, would be of great impor-
tance. In this work, we prepared SP-doped liquid crystal
(LC) microspheres, emulsified ina5%de xtrose (D-glu-
cose) solution, and showed that upon exposure to a
light-emitting diode (LED) with violet (405 nm) light,
the SP isoforms convert into their MS isoforms, which in
turn stimulates the MC isoforms to translocate across the
interface of the LC/dextrose solution, and interact with
the glucose molecules, leading to a lowering of the total
glucose concentration in the solution by 20 %.
2 EXPERIMENTAL PART
In the experiments, to prepare a photochromic mix-
ture, we used the following commercially available ma-
terials: as the LC host matrix ZLI-1639 (from Merck), as
the photochromic material SP-1’,3’,3’-Trimethyl-6-ni-
tro-1’,3’-dihydrospiro [chromene-2,2’-indole] and
macromonomer poly (vinyl alcohol) – (PVA) with an av-
erage molecular weight – Mw 55,000–65,000 g·mol
–1
(both from Sigma-Aldrich). Figure 1 shows 3D and 2D
structures of the SP and MC isoforms controlled by light
or temperature.
An SP-doped LC mixture was prepared by doping the
LC host substance with the SP material with the follow-
ing concentration ratio: 99.9 % ZLI-1639 + 0.1 % SP.
The prepared SP-LC mixture was stirred in its isotropic
phase at about 80 °C for 10 min using a laboratory glass
vial. To investigate the absorption behavior of the SP-LC
mixture upon exposure to light, we first built a planar op-
tical cell using two glass plates. A 99.4 % water + 0.6 %
PVA solution was deposited on the glass substrates by
spin-coating and then rubbed to obtain planar alignment
of the LC material. The spacing between the plates was
set to 24 μm, using Mylar films. The SP-LC mixture was
infiltrated by capillarity inside the optical cell. The
SP-doped LC microspheres were obtained by emulsify-
ing the SP-LC material ina5%de xtrose solution, the
name of a simple sugar made from corn or wheat that is
G. PETRIASHVILI et al.: LIGHT-STIMULATED LOWERING OF GLUCOSE CONCENTRATION ...
120 Materiali in tehnologije / Materials and technology 57 (2023) 2, 119–125
Figure 1: 3D and 2D structures of an SP (closed) and MC (opened)
molecule and light-controlled reversible molecular conformations of
SP and MC isoforms

chemically identical to glucose or blood sugar. Petri-dish
containers (a diameter of 4 cm, height of 2.5 cm) filled
with SP-LC/dextrose emulsions, were used to enclose
the substances. Emulsions were poured into cuvettes
with 1 cm gaps, transparent in the UV/visible ranges of
the optical spectrum. To obtain a light-stimulated
SP-to-MC conversion, we irradiated samples using an
LED, with an emission peak at 405 nm of the optical
spectrum. The distance from the LED to the SP-LC/dex-
trose emulsion was set at 10 cm. The light intensity on
the sample surface, measured with an optical power/en-
ergy meter, was 0.25 mW/cm
2
. An optical microscope
(OM) served for the visualization of the substance at the
microscale level. The absorption spectra of the SP-LC
mixture and SP-LC/dextrose emulsion were collected us-
ing an optical fiber-coupled spectrometer (Ava-Spec
AVS-2048-2) having a 1 nm resolution. Experiments
were carried out at 37 °C. To precisely measure the vol-
ume of the solutions, we used a laboratory pipette with a
0.01 mL accuracy. For the vigorous agitation of the
SP-LC/dextrose and SP-LC/water emulsions, we utilized
a magnetic stirrer hot plate (MSHP) with variable speed
settings ranging from 100 to 2500 min
–1
, with a con-
trolled mixing speed. The MSHP heats samples with a
0.2 °C accuracy, from ambient temperature to 300 °C.
The expanded beam, 40 mm in diameter, is incident on a
Petri dish filled with the emulsions. To study the light-in-
duced absorption spectra of the SP-LC mixture, we irra-
diated an optical cell with an LED. During 12 min of ex-
posure, the maximum absorption of the SP-LC mixture
was increased significantly from 0.05 to 2.5 arbitrary
units. In Figure 2, Curve 1 corresponds to the absorption
before the light irradiation. Curves 2, 3, 4 and 5 show the
absorption peaks after (2, 6, 10 and 12) s of exposure, re-
spectively.
The experimental set-up for the preparation, irradia-
tion and monitoring of the SP-LC/dextrose and
SP-LC/water emulsions is depicted in Figure 3. The
emitted light is directed normally to the emulsions lo-
cated in a Petri dish container. The backscattering image
of the emulsions is detected and captured by the OM
coupled with a high-resolution CCD camera. The dis-
tance from the LED to the upper surface of the samples
is set at 10 cm. To monitor the glucose concentration in
the SP-LC/dextrose emulsion, before and after the light
irradiation, we used a standard, clinically validated glu-
cose meter (GLM), which accurately measures the cur-
rent blood glucose using a finger stick blood sample
placed on a test strip and inserted into the device.
For the preparation of the SP-LC/dextrose emulsion,
5 mg of SP-LC mixture was extracted from a glass vial
and dropped in the Petri dish container filled with 75 mL
o f5%d e xtrose solution. The emulsion was mixed at
about 37 °C for 20 min, at 800 min
–1
. Since the SP-LC
and dextrose solutions are immiscible, this procedure is
functional for forming SP-LC microspheres with their
sizes depending on the stirring speed and duration. First,
the non-irradiated SP-LC/dextrose emulsion was ex-
tracted from the Petri dish container and poured into a
cuvette with a laboratory pipette; then the light absorp-
tion was measured using a spectrometer. Then we carried
out the above-described procedures to prepare the
SP-LC/dextrose emulsion, but in this case, during the
mixing, the SP-LC/dextrose emulsion was irradiated for
12 min with the LED. The obtained emulsion was ex-
tracted from the Petri dish container, poured into the
cuvette, and the absorption spectrum was measured
again using the spectrometer. In Figure 4, the left part
shows the absorption curves of the SP-LC/dextrose
emulsion before (a) and after (b) light exposure, and the
right part of the figure shows the cuvettes where the left
G. PETRIASHVILI et al.: LIGHT-STIMULATED LOWERING OF GLUCOSE CONCENTRATION ...
Materiali in tehnologije / Materials and technology 57 (2023) 2, 119–125 121
Figure 3: Experimental set-up for the preparation, irradiation and ex-
amination of SP-LC/dextrose and SP-LC/water emulsions
Figure 2: Absorption dependence on the exposure time for mixture
99.1 % ZLI-1639 + 0.1 % SP when irradiated with the LED

cuvette (a) is filled with the SP-LC/dextrose emulsion
before exposure to LED, and the right cuvette (b) is
filled with the emulsion after exposure to LED. As seen
in Figure 4, the absorption spectra of the SP-LC/dex-
trose emulsion without and with irradiation differ signifi-
cantly. In particular, compared to the non-irradiated sam-
ple, there is a significant increase in the light absorption
of the irradiated emulsion in the near UV and visible
ranges of the optical spectrum with absorption maxima
at 380 nm and 495 nm. Here we note that the absorption
peak of glucose is located at 285 nm of the optical spec-
trum.
Next, we compared the absorption spectrum of an
SP-LC/dextrose emulsion with the absorption spectrum
of an SP-LC/water emulsion. For this purpose, we filled
a Petri dish container with distilled water and dropped
the SP-LC solution into the water at such a concentration
ratio as described above. The obtained solution was
mixed at about 37 °C for 20 min, at 800 min
–1
. The same
procedure as in the SP-LC/dextrose emulsion case was
repeated and the absorption spectra of the SP-LC/dex-
trose emulsion (a) and SP-LC/water emulsion (b) were
compared. It was found that compared to the absorption
spectrum of the SP-LC/dextrose emulsion, the absorption
spectrum of the SP-LC/water emulsion further increases
in the near UV and visible part of the optical spectrum
with absorption maxima at 385 nm and 505 nm, respec-
tively. The left part of Figure 5 shows the absorption
spectra of the SP-LC/dextrose (a) and SP-LC/ water (b)
emulsions after 12 min of exposure, while the right part
of Figure 5 demonstrates the cuvettes filled with the ir-
radiated SP-LC/dextrose emulsion (a) and irradiated
SP-LC/water emulsion (b).
Figure 6 shows the SP-LC/dextrose emulsion under
the OM, placed in a Petri dish container before (a) and
after (b) the light irradiation. The emulsion before and
after the exposure to LED markedly differs. The non-ir-
radiated emulsion is milky in color, while the irradiated
emulsion is reddish purple.
Next, we monitored the light-controlled glucose con-
centration in the SP-LC/dextrose solutions using a porta-
ble glucometer based on the enzymatic biosensing tech-
nology. Its mechanism relies on the enzymatic
electrochemical detection of glucose and involves the
sampling of capillary blood from a finger to be analyzed
with the use of test strips and a glucometer.
13
To measure
the glucose concentration in the blood, the following
standard and popular units are used: mg/dL and mmol/L.
Therefore, we used a glucometer to convert the glucose
concentration from percent to mg/dL units. First, we
G. PETRIASHVILI et al.: LIGHT-STIMULATED LOWERING OF GLUCOSE CONCENTRATION ...
122 Materiali in tehnologije / Materials and technology 57 (2023) 2, 119–125
Figure 4: Absorption spectra of the non-irradiated and irradiated
emulsions (left part of the picture) and the cuvettes filled with emul-
sions before and after irradiation with LED (right part of the picture)
Figure 6: Optical microscope images of SP-LC/dextrose emulsion: (a) before and (b) after exposure to LED
Figure 5: Absorption spectra (the left part of the figure) and the
cuvettes filled with irradiated SP-LC/dextrose and SP-LC/water emul-
sions (the right part of the figure)

measured the glucose concentration ina5%de xtrose so-
lution. Then the dextrose solution was diluted several
times with distilled water, and the glucose level in the re-
sulting mixture was measured each time. We found that
5 % dextrose corresponds to 500 mg/dL (or
27.78 mmol/L), while 2.5 % dextrose corresponds to
250 mg/dL, etc. We first measured the glucose concen-
tration ina5%de xtrose solution using a glucometer to
study the variation in the glucose concentration as a
function of exposure time. After that, we prepared the
SP-LC/dextrose emulsion and exposed it to the LED for
1 min, 2 min, and so on for 12 min. After each LED ex-
posure, the SP-LC/dextrose emulsion was extracted from
the Petri dish container with a test strip, and the glucose
level was measured using the glucometer. The experi-
ments were carried out ten times, and the obtained data
were calculated as the arithmetic means according to
Equation (1):
En Et
n
t n
() ()
∑ ∑
(1)
where n is the number of experiments conducted, and t
is the exposure time. In our case, the number of experi-
ments is 10, and in each experiment, the exposure time
varied from 0 min to 12 min. Accordingly, Equation (1)
can be rewritten as follows:
En Et
t n
() ()
= =
∑ ∑
0
12
1
10
10
(2)
Based on Equation (2), we plotted the variation in the
glucose concentration in the SP-LC/dextrose emulsion as
a function of exposure time. As shown in Figure 7, upon
exposure to LED, the glucose concentration in the
SP-LC/dextrose emulsion gradually decreases by 20 per-
cent over 12 min. Interestingly, the concentration of glu-
cose in the emulsion rapidly decreases at the beginning
of irradiation, while further decrease in the glucose con-
centration slows down during irradiation.
We note that after the LED is turned off, the glucose
concentration in the SP-LC/dextrose emulsion increases
over time. However, this increase is insignificant and
never returns to its original level.
3 RESULTS AND DISCUSSION
The photochromism of SPs arises from a light-driven
ability to isomerize between the SP and MC forms. The
stable state of an SP is a non-colored closed molecular
form that can be transformed into its MC state upon irra-
diation with UV/violet light. More specifically, the car-
bon–oxide bond of SP molecules is cleaved when it is
transformed into the polar-colored MC form. Ref.
14
shows that upon exposure to UV/violet light, the
photochromic molecules inside LC microspheres experi-
ence an interconversion from the hydrophobic, oil-solu-
ble, non-polar SP state to the hydrophilic, water-soluble,
highly polar MC state. Light-induced photoisomerization
destabilizes the LC/water interface, stimulates the
translocation of MC molecules across the LC/water bar-
rier, and results in their homogeneous distribution
throughout the aqueous environment. Similarly, in our
experiments, upon exposure to LED, the SP molecules
doped in LC microspheres are photoisomerized from the
SP isoforms to the MC ones, which in turn causes MCs
to translocate through the LC/dextrose barrier, and
spread evenly in the dextrose solution. Figure 8 shows
the emulsion before exposure to LED (a) and after expo-
sure to LED (b).
To describe the interaction of the MC molecules with
D-glucose molecules, we used the Chem Draw Ultra
software. Based on the calculations, we found that the
electronegativity of the oxygen of the OH group of MC
is –0.301345. On the other hand, the electronegativity of
the oxygen of the hemiacetal hydroxyl group of the car-
bon atom (C1) of D-glucose is –0.397001. Therefore, we
guess that due to its high electronegativity, the
G. PETRIASHVILI et al.: LIGHT-STIMULATED LOWERING OF GLUCOSE CONCENTRATION ...
Materiali in tehnologije / Materials and technology 57 (2023) 2, 119–125 123
Figure 8: Photoinduced isomerization of an SP-MC molecule, fol-
lowed by the MC isoform’s translocation through the LC/dextrose so-
lution’s barrier
Figure 7: Change in glucose concentration in SP-LC/dextrose emul-
sion as a function of LED exposure time

hemiacetal hydroxyl oxygen of the glucose binds to the
carbon of MC. The OH group of MC forms water with
the hydrogen of glucose. The interaction between MC
and glucose gives the following compound: 2-(hydro-
xymethyl)-6-(4-nitro-2-((Z)-2-((R)-1,3,3-trimethylindo-
lin-2yl)vinyl)phenoxy)tetrahydro-2H-pyran-3,4,5-triol,
whose structural formula and 3D ball-and-stick model is
shown in Figure 9.
We assume that MC molecules act as inhibitors of
glucose molecules, causing the glucose concentration to
lower in the SP-LC/dextrose emulsion. However, despite
the obtained results, several issues need to be addressed.
The first challenge is the low penetration of violet light
into the tissue, and the second challenge is linked to vio-
let light that can photo-damage the tissue. The real solu-
tion to these challenges is the two-photon absorption
phenomenon stimulating the SP-MC photoisomerization.
Compared with single-photon violet-light excitations, the
two-photon near-infrared (NIR) excitations can dramati-
cally increase light penetration into the tissue because
cellular systems absorb much more weakly in this range
of the optical spectrum. Besides, in comparison with vio-
let light, NIR photons have the potential to cause less
photodamage to the tissue and living cells. In our experi-
ments, the average size of the obtained LC microspheres
was in a range of 5–20 μm. For real applications, the av-
erage size of the microspheres must be reduced to
submicron dimensions, which is achievable by control-
ling the stirring speed. On the other hand, we note that
an alternative and effective solution to these challenges
may be pre-irradiation of the SP-LC mixture poured into
a container, followed by administering the activated sub-
stance to the human body by injection or orally.
4 CONCLUSIONS
This study investigated a light-stimulated glu-
cose-lowering effect in an SP-LC/dextrose emulsion
based on SP-MC photoisomerization phenomena. We
have shown that upon exposure to the LED with violet
(405 nm) light, SP isoforms are converted to MS
isoforms, followed by their translocation across the
LC/dextrose interface and interaction with the glucose
molecules. This process causes the lowering of the total
glucose concentration in a solution by 20 %. We expect
that the proposed modality could provide a possibility to
dynamically regulate the concentration of glucose in the
blood with the required dose and at the appropriate time
to manage and treat type 2 diabetes noninvasively.
The authors confirm that the paper is original and has
not been published in this form anywhere else and it is
not under consideration for publication elsewhere.
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