Transfersomes for Optimal Penetration of α-Mangostin (Garcinia
mangostana L.) in Cosmetic Products using Vortexing-Sonication
Deby Tristiyanti 1,2, Yola Desnera Putri*1, Wahyu P Legowo1, Nia K Sari1, Sriwidodo2
1Sekolah Tinggi Farmasi Indonesia, Bandung, West Java, Indonesia
2Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy,
Universitas Padjadjaran, Sumedang, Indonesia
Submitted: 08/12/2023, Revised: 10/07/2024, Accepted: 20/12/2024, Published: 24/01/2025
ABSTRACT
Produk kosmetik berbasis transfersom semakin menarik perhatian karena
teknologi nano vesikel ini dapat meningkatkan penetrasi bahan aktif seperti isolat
manggis dari Garcinia mangostana L. ke dalam kulit. Teknologi ini menawarkan
pengembangan produk kosmetik inovatif yang menjanjikan. Transfersom terdiri
dari fosfolipid (yaitu fosfatidilkolin dari lesitin kedelai) dan surfaktan yang
masing-masing membentuk vesikel dan meningkatkan fleksibilitas transferom
sebagai aktivator tepi. Kami mengembangkan formula dengan isolat manggis
dalam transfersom dan mengukur ukuran partikel dan persen penjebakan bahan
aktif. Rasio yang digunakan adalah F1 (60:40), F2 (50:50), dan F3 (95:5). Setelah
dioptimasi, formula dievaluasi untuk efisiensi penyerapan dan stabilitas fisik
selama penyimpanan. Penelitian ini membuat transfersom dari isolat mangostin
dengan metode vortexing-sonikasi dan homogenizer. Ukuran partikel diukur
dengan alat analisis ukuran partikel dan efisiensi penyerapan dengan
spektrofotometer UV-Vis. Hasil penelitian menunjukkan bahwa formula
transfersom terbaik adalah F2 (50:50), dengan ukuran partikel 433,2 nm, PDI
0,399, zeta potensial -2,43 mV, dan efisiensi penjerapan 99,08%. Transfersom ini
berpotensi sebagai sistem penghantaran isolat mangostin yang efisien ke dalam
kulit dan dapat disimpan dengan lebih baik pada suhu dingin.
Key words: Transferom, vortexing-sonikasi, isolat manggis
Vol. 5, Issue 2, 2023 (432-440)
http://journal.unpad.ac.id/IdJP
*Corresponding author,
e-mail: yoladesneraputri@gmail.com (Y. D. Putri )
https://doi.org/10.24198/idjp.v5i2.51593
© 2023 Y. D. Putri et al
433
1. Introduction
Alpha mangostin (α-mangostin) as
isolates of Garcinia mangostana L have
high antioxidant activity as a DPPH
radical scavenger1. Mangosteen rind
mainly contains xanthones, namely α-
mangostin, and other secondary
metabolites such as flavonoids, and
tannins2.
The delivery of active ingredients
in cosmetic products used topically is
often used, yet transdermal delivery for
systemic action is relatively new, and
research in this field is currently
developing very quickly. The transdermal
route may deliver compounds with low
solubility in water and those with low oral
bioavailability. Further, it is a non-
invasive drug delivery route through the
skin or epidermis, dermis, and other
layers into the systemic circulation3.
The main problem with this
transdermal active ingredient delivery
system is that it has a layer, the stratum
corneum, that makes it difficult for
molecules coming from outside to
penetrate. This layer is tightly packed,
making it difficult to penetrate the skin,
which can hamper the transdermal route4.
Transfersomes are more advantageous
than the liposome system as a nanovesicle
system because they can penetrate
the skin with smaller pores.
Transfersomes can deliver drugs with
various solubility properties and have
elastic properties that allow them to pass
through gaps 5 to 10 times smaller in size
without losing their shape5.
The components that formq
transfersomes consist of phospholipids in
the form of phosphatidylcholine as a
vesicle-forming component, surfactants
as edge activators that function to
increase the flexibility of the
transfersomes, and buffer solutions as a
hydration medium. The composition of
phospholipids and surfactants is a
variable that can affect the optimisation
of the transfersomes formula6,7.
Therefore, this research was carried out to
determine the most stable and better
formula based on its characterisation and
determine the effect of storage at different
temperatures.
1.1. Materials and Methods
The mangostin (Garcinia
mangostana L.) isolate used was
from….., Apa bahan pure mangostin
isolate yang digunakan untuk menghitung
persen adsorbtion? soybean lecithin,
Tween 80, methanol pro analysis,
phosphate buffer pH 7.4, and distilled
water. We also used analytical balances, a
particle size analyser/zetasizer (Horiba®,
japan), homogeniser, Ostwold viscometer
, pH meter (Mettler Toledo, Germany),
and a UV-Vis spectrophotometer
(Genesys 10S Uv-Visible, Thermo
Scientific, New York, NY, USA).
1.2. Preparation of Mangostin isolates
Transfersomes
Optimization of the transfersomes
formula was carried out using the
vortexing-sonication method using a
homogenizer. The components for the
transfersomes were soy lecithin and
tween 80 as the surfactant. Variation of
soy lecithin and tween 80 were prepared
to obtained the optimum formula. Soy
lecithin and tween 80 were mixed first,
then 0.001 gram of mangostin isolate was
added, followed by 100 ml of hydrated
with phosphate buffer pH 7.4. Hydration
was carried out to form a lamellar
structure that formed a ball-like bilayer.
To do the mixing and reduce the size of
the vesicles formed, ultra turrax
homogenizer is needed at 8000 rpm for
30 min. Following, an evaluation
Y. D. Putri et al / Indo J Pharm 5 (2023) 432-440
434
was carried out with transfersomes
storage, including storage temperatures
(<25˚ C and at >25˚ C). The formulation
optimisation of transfersomes from
mangosteen isolates is listed in Table 1.
Y. D. Putri et al / Indo J Pharm 5 (2023) 432-440
Table 1 Transfersomes Formula
Formula Soybean lecithin: tween 80
1
2
3
60:40
50:50
95:5
1.3. Particle Size Distribution and
Polydispersity Index
Particle size distribution is an
important factor in nanoparticle
preparations. The test is determined using
a particle size analyser (PSA). The PSA
was used with the Dynamic Light
Scattering (DLS) method at 25 oC that
utilizes the principle of Brownian motion,
in which the particles and molecules of a
dissolved sample are in constant random
thermal motion8.
Polydispersity index
The polydispersity index is a
parameter that shows the homogeneity
and uniformity of particle sizes in a
nanoparticle preparation. A polydispersity
index value of <0.5 has a homogeneous
size distribution range or indicates a
homogeneous vesicle with high physical
stability. The closer the polydispersity
index value is to zero, the vesicle size
will be more homogeneous9.
1.4. Zeta Potential
This zeta potential measurement
was carried out to predict the stability of
the dispersion formula. Preparations in
the form of nanoparticles with a zeta
potential value of <-30 mV and >30 mV
have higher stability because the particles
in the dispersion system also
have a zeta potential value of <-30 mV
and/or >30 mV and a mutual repulsive
force, and thus no tendency to merge and
flocculate10.
1.5. Adsorption Efficiency
The levels were calculated using
the UV-Vis Spectrophotometric
calibration curve, constructed from a pure
mangostin isolate at serial concentrations
of 5, 10, 15, 20, 25, and 30 ppm. The
equation of each concentration series was
calculated with the maximum wavelength
of mangosteen isolate obtained using a
Uv-Vis spectrophotometer, from which a
linear regression equation was
determined.
The adsorption efficiency (EP)
test was carried out with centrifugation
ultracentrifugation to separate the active
mangostin isolate, which was not
adsorbed. Speed was set at 6000 rpm for
30 min. After the supernatant and
precipitate were formed, the free
mangostin isolate was obtained from the
supernatant, and the absorption was
measured using a Uv-Vis
Spectrophotometer. Drug levels were
determined using the absorbance data
obtained11. The adsorption efficiency (%
EP) was calculated using the following
formula:
% 𝐸𝑃 =𝑇𝐷 − 𝐹𝐷
𝑇𝐷 𝑥 100%
435
where TD is the total compounds
contained in the formula and FD is the
number of compounds detected in the
supernatant (not adsorbed).
1.6. Evaluation of Transfersomes
Preparations
The evaluation was conducted
by organoleptic observation to determine
the physical properties of the
preparations, including shape, color, and
odor to evaluate whether physical
changes occur during storage. The pH of
the preparation was measured using a pH
meter calibrated using standard buffers
(i.e. pH 4, pH 7, and pH 9) at room
temperature. The viscosity was
determined using an Ostwald viscometer.
2. Result
Optimization of the transfersomes
formula was achieved by comparing the
concentrations and differences in the
temperature storage (at <25 ˚C and
>25˚C) to determine a good and stable
base for storage. Transfersomes were
made based on the comparison of the
concentrations of phosphatidylcholine
and Polysorbate 80 used. The
transfersomes were evaluated on days 0,
4, 7, 14, 21, and 28 at the various storage
temperatures. The organoleptic properties
of the transfersomes stored at room
temperature on day 4th in formulas F1 to
F3 showed precipitates. Similarly, the
transfersomes stored in the climatic
chamber produced sediment, while the
transfersomes stored at low temperatures
showed stable results for formulas F1 and
F3 but on the 18th day and with the
appearance of plaques, except for the
formula F2.
Y. D. Putri et al / Indo J Pharm 5 (2023) 432-440
Figure 1. Preparation of Transfersomes
The results of the pH evaluation of the
transfersomes stored at different
temperatures did not show significant
changes in pH, resulting in an average pH
of 6–7. The conditions set in this study
allowed the skin to adapt to the pH of
4.5–8
of the preparation15. The viscosity of the
transfersomes produced an average value
of 0.74 cP, which is influenced by the
relationship between the length of the
flow time; the longer the flow time, the
greater the viscosity of a liquid, while the
shorter the flow time, the lower the
viscosity and size of the liquid. Therefore,
the F2 formula with a 50:50 ratio was
chosen to be added to the mangostin
isolate at 0.001 gram/mL.
436
Y. D. Putri et al / Indo J Pharm 5 (2023) 432-440
3. Discussion
Transfersomes preparations are
used as a delivery medium through the
skin. The manufacturing method used for
mangostin isolate-transfersomes
preparations used vortexing-sonication or
the direct stirring method. This method
can produce transfersomes isolates of
mangosteen that tend to have better
physical stability and particle size. This
method can assist in producing a more
uniform transfersomes structure with a
smaller particle size16.
From the analysis of the
transfersomes preparations using the PSA
and measured in triplicates, the results
were obtained in the form of PDI data or
polydispersity index, which indicates the
homogeneity of the particle size
distribution. The smaller the resulting
PDI value or close to zero, the more
uniform the particle size distribution is14,
while the Z- Average indicates the
average particle size produced. Based on
the Z-Average data, the particle size in
the transfersomes F2 produces a value of
433.2 nm ±SD (Figure 2). The results of
the measurements performed show that
the transfersomes vesicle meets the
transfersomes requirements for a vesicle
size range of 100–400 nm, which is
included in the large unilamellar vesicle
(LUV) category4.
The vesicle size of the
transfersomes is also affected by the
particle size reduction that used an
ultraturax homogenizer at 8000 rpm
because it is influenced by higher speeds
and produces greater frictional forces and
more efficient breakdown. Likewise, the
results of the polydispersity index test
yielded a value of 0.399 (Table 2). If the
polydispersity index value produces a
value of <0.5, then vesicles are
homogeneous with high stability.
Table 2. Transfersomes Particle Size Distribution and Polydispersity Index of F2.
No of
Testing Size(nm) Polydispersity
Index
Testing 1
Testing 2
Testing 3
Average
426.5
437.1
436.1
433.2
0.394
0.415
0.390
0.399
Figure 2. Particle size distribution of the transfersomes produced
437
Y. D. Putri et al / Indo J Pharm 5 (2023) 432-440
The zeta potential measurement
was used to determine the stability of the
preparation against storage conditions and
to know the ability of particles to
aggregate again increasing the particle
size16. The particle may be stable if it has
a potential value of >30 mV or >-30 mV
in the presence of repulsive forces
between particles with the same charge
that can avoid aggregation and avoid
combination to form larger particles.
Based on the zeta potential obtained,
formula 2 produced a value of -2.43
(Table 3 and Figure 3).
Table 3. Transfersomes Zeta Potential.
Formula 2 Testing
Zeta Potential (mV)
Testing 1
Test 2
Testing 3
Average
-2.7
-2.3
-2.3
-2.43
Figure 3. Zeta Potential Measurement
The entrapment efficiency test
was carried out to determine the effect of
the concentration of the active substance
on its adsorption in the vesicles.
Adsorption efficiency can be used as the
main parameter in determining the
formula for the manufacturing of
nanovesicles. The amount of free
mangostin isolate was separated using
ultracentrifugation at 6000 rpm for 30
min. The absorbance of the supernatant
resulting from centrifugation was
measured using a spectrophotometer to
determine the level of mangostin isolate
that was not absorbed. The results of the
equation from linear regression were:
y=0.0535x - 0.022 with a mark
coefficient correlation of 0.97.
The measurements of mangostin
isolates that were absorbed in the
transfersomes showed a 99.08% yield.
The requirement for adsorption efficiency
in transfersomes was not <60%, showing
that the research carried out on
transfersomes preparations containing
mangostin isolate met the requirements
because it was >60% with an adsorption
efficiency level of 99.08%. The higher the
adsorption efficiency value, the higher the
skin penetration ability and the smaller
particle size. Further, it can increase the
flexibility of the lipid bilayer membrane,
thereby allowing the transfersomes to
pass through pores that are smaller than
the size of the vesicle spontaneously.
438
Y. D. Putri et al / Indo J Pharm 5 (2023) 432-440
The entrapment efficiency test
was carried out to determine the effect of
the concentration of the active substance
on its adsorption in the vesicles.
Adsorption efficiency can be used as the
main parameter in determining the
formula for the manufacturing of
nanovesicles. The amount of free
mangostin isolate was separated using
ultracentrifugation at 6000 rpm for 30
min. The absorbance of the supernatant
resulting from centrifugation was
measured using a spectrophotometer to
determine the level of mangostin isolate
that was not absorbed. The results of the
equation from linear regression were:
y=0.0535x - 0.022 with a mark
coefficient correlation of 0.97.
The measurements of mangostin
isolates that were absorbed in the
transfersomes showed a 99.08% yield.
The requirement for adsorption efficiency
in transfersomes was not <60%, showing
that the research carried out on
transfersomes preparations containing
mangostin isolate met the requirements
because it was >60% with an adsorption
efficiency level of 99.08%. The higher the
adsorption efficiency value, the higher the
skin penetration ability and the smaller
particle size. Further, it can increase the
flexibility of the lipid bilayer membrane,
thereby allowing the transfersomes to
pass through pores that are smaller than
the size of the vesicle spontaneously.
Transfersomes isolate mangostin
produced was yellowish-white in colour.
The resulting colour was due to the active
ingredients used, namely mangostin
isolate and soy lecithin. These
transfersomes had a characteristic smell
of lecithin. The transfersomes that were
stored at low temperatures did not settle
or no separation occurred, whereas
transfersomes that were stored at low
temperatures in the climatic chamber had
sedimentation within the first week
The results of the pH testing in the
formulas obtained with two storage
temperatures (i.e. cold temperatures and
climatic chambers) show that the pH
testing produced values in the range of 6–
7. Viscosity was determined using an
Ostwold viscometer. It is important to
measure viscosity because it shows the
resistance of a liquid to flow. The factors
that affected the viscosity included the
mixing or stirring process during the
preparation, and the selection of
thickeners and surfactants used. The
viscosity measurements on transfersomes
preparations containing mangostin isolate
during week 0 to week 4 were in the
range of 4–8 cps. The difference in flow
viscosity was related to the presence of
suspended particles.
4. Conclusions
A mangostin isolate was used in
transfersomes preparations as an active
substance. Mangostin isolates must be
able to penetrate the skin and reach
subcutaneous adipose tissue as its target.
The entrapment efficiency value obtained
from the UV-Vis Spectrophotometer
method showed that the entrapment
efficiency value of the mangostin isolate
was 99.08%. The storage results of
transfersomes preparations stored at <
25˚C and >25˚C for one month showed
that the transfersomes preparations stored
at cold temperatures show
organoleptically more optimal
preparations.
439
Y. D. Putri et al / Indo J Pharm 5 (2023) 432-440
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