Article

Characterization and In Vivo Evaluation of Durian Peel Extract in

Nanoliposome Transdermal Patch for Wound Healing

Nindita Clourisa Amaris Susanto

1

*

,

Milkazia Elda Putri

1

,

Dayinta Tyas Utami

1

,

D

ian Eka Ermawati

1

, Heru Sasongko

1

, Sholichah Rohmani

1

Anif Nur Artanti

1

, Diyah Tri

Utami

1

, M. Fiqri Zulpadly Mh

1

, Ulfa Afrinurfadhilah Darojati

1

,

Annisa Diyan Meitasari

1

,

Meta Kartika Untari

1

,

Alifina Izza

2

1

Department of Pharmacy, Vocational School, Sebelas Maret University, Indonesia

2

Master of Public Health, Faculty of Health, Medicine and Behavioural Science (HMBS), The University of

Queensland, QLD, Australia

A

bstract

Wounds are a form of continuous damage due to loss of tissue, structure and anatomical function of

the skin caused by heat trauma or sharp object scratches. The prevalence of wound injury patients in

Indonesia is 9.2%. One of the natural ingredients that is effective inhibiting

the growth of infectious

organisms is durian, especially in its peel. In this study, durian peel was formulated in liposome dosage

form and applied to patch preparations. The purpose of this study was to assess the effectiveness of

durian

skin

extract

liposomes

(

Durio

zibethinus

Murr.)

for

wound

healing

in

white

rats.

Durian

peel

(Durio

zibethinus)

extract

was

prepared

by

maceration

using

70%

ethanol

and

analyzed

for

phytochemical content and total flavonoids. The extract was formulated into liposomes using the thin-

film

hydration

method

and

optimized

by

simplex

lattice

design.

Liposomes

were

characterized

and

incorporated into a transdermal patch, followed by physicochemical evaluation. Wound healing activity

was tested in male Wistar rats with incision wounds and observed for seven days, and the data were

statistically analyzed. The results of this study are that the patches produced can provide a therapeutic

effect on the healing of incision wounds in wistar strain male white rats (

Rattus

norvegicus

L.) with a

healing

percentage

on

day

7

th

of

72.5%

which

is

characterized

by

the

absence

of

edema,

bleeding,

growth of fur in mice, the appearance of scabs and wound closure.

Keywords:

Antioxidant activity; Durio zibethinus; drug delivery system; flavonoid; skin regeneration.

*

Corresponding author

Email addresses: nindita_clourisa@staff.uns.ac.id (NCA Susanto)

DOI:

https://doi.org/10.22437/chp.v10i1.48779

Received

Octobe 05

th

2025;

Accepted

May 17

th

2026;

Available online

June 30

th

2026

(

https://creativecommons.org/licenses/by/4.0

)

154

Graphical Abstract

Introduction

Wounds

are

a

form

of

tissue

damage

characterized

by

the

loss

of

skin

structure

and anatomical function caused by trauma

such

as

heat

exposure,

mechanical

injury,

or

sharp

object

scratches

[1].

The

prevalence of wound injuries in Indonesia is

reported

to

be

approximately

9.2%,

indicating

that

wound

management

remains an important health concern. One

of

the

most

common

types

of

wounds

is

incision wounds, which occur due to trauma

caused

by

sharp

objects.

Proper

wound

management

is

essential

to

prevent

infection and accelerate tissue repair. In this

context, antimicrobial agents are commonly

used

to

reduce

the

risk

of

infection,

while

antioxidant agents play an important role in

accelerating

the

healing

process

by

reducing

oxidative

stress

and

preventing

further cellular damage [2].

In

recent

years,

the

use

of

traditional

medicine has gained increasing attention as

an

alternative

therapeutic

approach.

Traditional

medicinal

plants

are

widely

considered

safer

than

synthetic

drugs

because they generally produce

fewer side

effects

when

used

appropriately

[3].

In

addition,

many

medicinal

plants

contain

various

bioactive

compounds

that

exhibit

antimicrobial,

anti-inflammatory,

and

antioxidant

activities,

which

are

beneficial

for wound healing [4], [5].

One

plant

that

has

potential

as

a

natural

therapeutic

agent

is

durian

peel

(

Durio

zibethinus

).

Durian

is

widely

consumed

in

many tropical countries, and its peel is often

considered

agricultural

waste.

However,

several

studies

have

reported

that

durian

peel contains various bioactive compounds

such as flavonoids, alkaloids, and saponins

that

possess

antibacterial

and

antioxidant

activities.

These

bioactive

compounds

contribute

to

the

biological

properties

of

durian

peel

and

support

its

potential

155

NCA Susanto et al.,

Chempublish Journal, 10(1) 2026, 154-170

utilization in pharmaceutical and biomedical

applications [6].

Among

these

compounds,

flavonoids

play

an

important

role

as

natural

antioxidants.

Flavonoids

can

neutralize

free

radicals

and

reduce

oxidative

stress

by

inhibiting

the

formation of reactive oxygen species (ROS),

which

are

responsible

for

cellular

damage

and

delayed

wound

healing.

By

reducing

oxidative

stress

and

inflammation,

flavonoids can promote tissue regeneration

and

accelerate

the

wound

healing

process

[7].

Although

durian

peel

contains

promising

bioactive compounds, the stability of these

compounds

is

often

limited

because

they

are sensitive to environmental factors such

as light, temperature, and oxidation. These

limitations may reduce the effectiveness of

the

active

compounds

during

application.

Therefore,

an

appropriate

drug

delivery

system

is

required

to

protect

the

active

compounds

and

enhance

their

therapeutic

effectiveness.

Liposomes

have

been

widely

studied

as

drug delivery systems due to their ability to

encapsulate

bioactive

compounds

and

improve their stability, biocompatibility, and

bioavailability

[8].

Liposomes

are

vesicular

structures

composed

of

phospholipid

bilayers that can carry both hydrophilic and

lipophilic

compounds.

have

reported

that

liposome

formulations

provide

higher

entrapment

efficiency

compared

to

other

vesicular

systems

such

as

niosomes.

For

example,

liposome

formulations

have

shown

an

entrapment

efficiency

of

approximately

67%,

which

is

higher

than

that

of

niosome

preparations

that

demonstrate

around

24%

entrapment

efficiency

[9].

In

addition,

liposomes

can

improve

therapeutic

effectiveness

by

enhancing

compound

stability,

facilitating

tissue

penetration,

and

improving

biodistribution to target sites [10].

Therefore,

this

study

aimed

to

formulate

durian peel (

Durio zibethinus

) extract into a

liposome-based

system

and

incorporate

it

into

a

transdermal

patch

preparation.

The

liposome

formulation

was

characterized

and

evaluated

for

its

antioxidant

activity

and

physicochemical

properties.

Furthermore,

the

effectiveness

of

the

liposome-based

transdermal

patch

containing

durian

peel

extract

was

evaluated in vivo for incision wound healing

in white rats.

Materials and Methods

Materials

Durian peel (

Durio zibethinus

) was obtained

from

Karanganyar,

Central

Java,

Indonesia.

Experimental

animals

used

in

this

study

were

male

Wistar

rats

weighing

150–200

g

obtained

from

Karanganyar,

Central

Java,

Indonesia.

The

materials

used

included

cholesterol

(Sigma,

Missouri,

USA),

phosphatidylserine

(Nutricost,

Vineyard,

Utah,

USA),

polyvinylpyrrolidone

(PVP K-30)

(Nitra

Kimia,

Indonesia),

hydroxypropyl

methylcellulose

(HPMC)

(Sigma-Aldrich,

Missouri,

USA),

ethyl

cellulose

(EC)

(Sigma-

Aldrich,

Missouri,

USA),

propylene

glycol

(Dow

Chemical

Pacific,

Singapore),

ethanol

96%, and quercetin (Sigma, Missouri, USA).

Preparation

of

extract

durian

peel

(Durio

zibethinus)

The Durian peel (

Durio zibethinus

) was dried

using

an

oven

at

60

℃

for

1

day,

cut

into

small

pieces

and

ground

using

a

blender.

Extraction

was

carried

out

by

maceration

method

with

70%

ethanol

to

obtain

paste

extract

of

durian

peel

in

a

ratio

(1:10)

in

glass

jar

protected

from

direct

sunlight.

Maceration

was

done

by

soaking

the

simplisia powder in 70% ethanol solvent for

156

NCA Susanto et al.,

Chempublish Journal, 10(1) 2026, 154-170

3x24

hours.

The

filtrate

was

concentrated

with

a

waterbath

at

40

℃

to

get

a

good

yield.

The

paste

extract

was

obtained

by

drying in an oven at 105

℃

for 30 minutes

until a constant weight was obtained [11].

Phytochemical screening

Phytochemical

screening

of

Durian

peel

(

Durio

zibethinus

)

extract

using

standard

procedures

to

reveal

the

presence

of

chemical

constituents

such

as

alkaloids,

flavonoids,

tannins,

saponins,

and

triterpenoids [12].

Determination of total flavonoids content

10 mg Quercetin standard was dissolved in

ethanol, to make stock solution 1000 ppm.

The stock solution was diluted to 100 ppm

and

diluted

into

concentration

series

of

2

ppm,

4

ppm,

6

ppm,

8

ppm,

and

10

ppm.

Furthermore, 10 mg of extract was weighed

and

dissolved

in

ethanol

using

10

mL

volumetric flask. Serial solution and 1 mL of

extract

solution

were

taken,

added

0.2

mL

AlCl

₃

,

0.2

mL

potassium

acetate,

3

mL

ethanol, and aquadest 10 mL. The

mixture

was

incubated

for

30

minutes

at

room

temperature and the absorbance value was

analyzed using UV-Vis spectrophotometry at

a wavelength of 435 nm [13].

Preparation of liposome

The

optimal

formula

determination

in

this

study

was

used

the

simplex

lattice

design

method

with

Design

Expert

software

version 13. Optimization was carried out to

determine

which

cholesterol

and

phosphatidylserine

components

produced

the

optimal

formula.

The

responses

measured

were

antioxidant

activity

and

adsorption

efficiency.

Liposomes

were

prepared

by

dissolving

the

basic

ingredients:

cholesterol

and

phosphatidylserine

dissolved

with

chloroform

in

a

rotary

evaporator.

The

phosphate

solution

was

added

for

hydrating

the

liposome

thin

film

at

the

same

time

as

the

extract

was

added.

The

resulting liposomes were homogenized into

vesicles

using

an

ultrasonic

cell

disruptor

for

30

min

[13].

The

formulas

used

are

listed in Table 1.

Evaluation

and

characterization

of

liposome

Organoleptic

.

The

organoleptic

examination

was

done

by

visual

observation

based

on

shape,

color,

and

odour

compared

to

the

other

journal

studies

that

have

been

conducted.

pH test

. The test was carried out by inserting

the pH meter into the liposome preparation

for

5

seconds.

Then

observe

the

number

shown

on

the

pH

meter

screen.

The

obtained

results

were

compared

with

the

pH value of topical skin preparations [14].

Antioxidant activity test

The antioxidant activity was evaluated using

the

DPPH

free

radical

scavenging

assay.

A

1000 ppm stock solution of the extract was

prepared by dissolving 10 mg of the extract

in 10 mL of 96% ethanol. The stock solution

was subsequently diluted to obtain working

concentrations

of

20,

40,

60,

80,

and

100

ppm.

Similarly,

a

500

ppm

liposome

stock

solution

was

prepared

by

diluting

5

mL

of

the liposomal formulation with 96% ethanol

to

the

required

volume,

followed

by

serial

dilution

to

the

same

concentration

range

(20–100 ppm). For the assay, 1 mL of each

sample solution was mixed with 2 mL of 0.1

mM

DPPH

solution,

vortexed,

and

incubated in the dark at room temperature

for

30

min

to

allow

the

radical

scavenging

reaction

to

reach

equilibrium.

The

absorbance was then measured at 517 nm

using

a

UV–Vis

spectrophotometer,

with

96%

ethanol

as

the

blank.

The

percentage

of

DPPH

radical

scavenging

activity

was

157

NCA Susanto et al.,

Chempublish Journal, 10(1) 2026, 154-170

calculated,

and

the

IC

₅₀

value

was

determined

from

the

linear

regression

of

inhibition

percentage

against

sample

concentration.

All

measurements

were

performed in triplicate [15].

Characterization of particle size

Particle

measurement

of

liposome

preparation

was

done

by

taking

3

mL

of

liposome

preparation

and

putting

it

into

a

cuvette.

The

preparation

was

added

with

aqua

pro

injection.

The

cuvette

containing

the

sample

was

inserted

into

the

PSA

tool

holder [16].

Entrapment efficiency (EE) test

The

entrapment

efficiency

(EE)

of

the

liposome

preparation

was

carried

out

by

separating the unabsorbed durian fruit peel

extract

using

a

centrifugator

at

4,000

rpm

for

30

min.

The

results

of

the

separation

formed

supernatant

and

sediment.

Then

1mL

supernatant

was

diluted

in

10

mL

volumetric

flask,

and

added

distilled

water

until

the

limit

mark.

The

absorbance

value

of the supernatant was analyzed using UV-

Vis

spectrophotometry

at

a

wavelength

of

435 nm [14].

Characterization of FTIR

Observation

of

functional

groups

using

an

infrared spectrophotometer was carried out

on

samples

of

durian

peel

extract,

cholesterol

powder,

phosphatidylserine,

and liposome base by inserting the sample

into

the

FTIR

instrument

tube.

The

functional groups were identified based on

the

wavelength

and

intensity

of

the

absorption peaks.

Table 1

. Liposome formulation

Materials	Formulas
F1	F2	F3	F4	F5
Extract	10 mg	10 mg	10 mg	10 mg	10 mg
Cholesterol	30 mg	20 mg	40 mg	10 mg	50 mg
Phosphatidylserine	30 mg	40 mg	20 mg	50 mg	10 mg
Chloroform	10 mL	10 mL	10 mL	10 mL	10 mL
Phospate buffer	20 mL	20 mL	20 mL	20 mL	20 mL

Preparation of patch transdermal

The patch formulas used are listed in Table

2. The preparation of liposomes from

Durio

zibethinus

Murr.

durian

peel

extract

was

carried

out

using

the

lipid

layer

hydration

method.

The

first

step

was

to

dissolve

cholesterol

and

phosphatidylserine

in

an

organic

solvent,

chloroform,

then

add

the

Durio

zibethinus

Murr.

durian

peel

extract.

The

solution

mixture

was

then

evaporated

using a rotary evaporator at 30

℃

to obtain

a

thin

lipid

layer.

After

that,

the

lipid

layer

was hydrated using a phosphate buffer and

evaporated again using a rotary evaporator

for

15

min

to

form

a

homogeneous

suspension.

Evaluation of patch transdermal

Evaluation

of

transdermal

patch

preparation

includes

organoleptic

test,

pH,

weight

uniformity,

thickness,

folding

resistance,

moisture

content,

and

stability

test [17].

158

NCA Susanto et al.,

Chempublish Journal, 10(1) 2026, 154-170

Experimental animal preparation

Male

rats

of

3

months

Wistar

strains

weighing

150-200

grams

were

acclimatized

in

individual

cage

for

one

week

before

incision. The characteristics of the rats were

white,

red

eyes,

elongated

head

and

tail

that exceed the body’s length.

Wounding of rats

Lidocaine creams were used to anesthetize

of

rats

to

create

the

wound.

The

rat’s

hair

was shaved on the right and left sides of its

back.

Wounds

were

made

with

a

diameter

of 1-2 cm using a biopsy punch.

Table 2

. Patch formulation

Materials

Formulas

PF0

PF1

PF2

PF3

PF4

PF5

Liposome

0

5 mL

Liposome F1

5 mL

Liposome F2

5 mL

Liposome F3

5 mL

Liposome F4

5 mL

Liposome F5

HPMC

2 gr

EC

1 gr

PG

10 mL

Ethanol

40 mL

Aquadest

100 mL

Experimental design

The

injured

rats

were

divided

into

seven

groups

with

three

rats

in

each

group,

consisting

of

a

negative

control

group,

a

positive

control

group,

and

five

treatment

groups

treated

with

liposome

patch

formulations

PF1,

PF2,

PF3,

PF4,

and

PF5.

The

positive

group

was

given

povidone

iodine patches and the negative group was

given

patches

without

durian

peel

extract

liposomes.

The

liposomal

patch

treatment

was

applied

to

each

mouse

twice

a

day

in

the

morning

and

evening.

The

patch

was

sized 3x3cm [18].

Observation and data collection

The wound diameter of the mice (negative,

positive,

and

treatment:

patch

groups

with

various

concentrations)

was

measured

using a caliper on four sides of the wound

by

looking

at

the

average

wound

diameter

from

the

development

of

the

wound

healing

process

on

the

mice's

back

every

three days by comparing the wound healing

process

of

the

incision.

Observations

were

conducted

from

day

1

to

day

7

after

the

wound

was

created.

Measurements

using

the

percentage

conversion

formula,

the

wound

diameter

measurements were then

converted

into

the

percentage

of

healing

(%).

The

percentage

of

wound

healing

was

then

calculated

using

the

percentage

conversion equation 1 [18].

(1)

Where: Px : percentage of wound healing on

day x (in %); d1 : First day wound diameter

(cm); dx : wound diameter x day (cm).

159

NCA Susanto et al.,

Chempublish Journal, 10(1) 2026, 154-170

Data analysis

Data were analyzed using IBM SPSS Version

26.0 Shapiro wilk method to test normality,

levene

test

was

used

to

test

homogeneity

and

the

respective

differences

in

wound

healing

in

test

animals

using

kruskal

wallis

[18].

Result and Discussion

Plant determination

Determination

of

Durian

peel

(

Durio

zibethinus

)

conducted

in

laboratory

of

Biology

Study

Centre,

Faculty

Mathematics

and

Natural

Sciences,

Universitas

Sebelas

Maret,

Surakarta

with

the

certificate

number

of

019/UN27.9.6.4/Lab/2025

showed that the plant used was the species

D.

zibethinus

Murr.

Moisture content and yield

The durian peel symplisia is brown in color,

smells

like

durian,

slightly

rough

texture,

and has a moisture content of 5.56%, while

the extract obtained has a distinctive smell

of

durian

skin,

brown

color,

slightly

thick

texture,

and

yield

of

22.54%.

Durian

fruit

peel

(

Durio

zibethinus

Murr.)

used

in

this

formulation

has

a

good

moisture

content,

which

should

not

be

more

than

10%

and

the

extract

that

has

been

made

gets

a

better

yield

compared

to

the

yield

value

using

96%

ethanol

solvent

which

produces

a % yield of 16.84% [11].

Phytochemical screening

Phytochemical

screening

showed

that

the

durian

peel

extract

(

Durio

zibethinus

)

contained

several

bioactive

compounds,

including

alkaloids,

flavonoids,

tannins,

saponins,

and

triterpenoids.

These

results

are

consistent

with

that

reported similar phytochemical constituents

in durian peel extracts [12]. The presence of

these compounds suggests that durian peel

has significant potential for pharmaceutical

and biomedical applications. Flavonoids and

tannins

are

known

for

their

strong

antioxidant

activity,

which

can

reduce

oxidative

stress

and

support

tissue

regeneration

during

the

wound

healing

process. Meanwhile, alkaloids and saponins

exhibit

antimicrobial

properties

that

may

help

prevent

infection

in

wounds.

Similar

phytochemical

compounds

have

also

been

reported

in

other

plant

species

used

for

wound

healing,

indicating

that

these

metabolites

play

an

important

role

in

the

therapeutic effects of medicinal plants.

Several

studies

have

demonstrated

that

plant

extracts

rich

in

flavonoids

and

phenolic

compounds

show

strong

antioxidant

and

antibacterial

activities,

which

contribute

to

their

effectiveness

in

promoting

wound

healing.

Therefore,

the

presence

of

these

bioactive

compounds

in

durian

peel

extract

supports

its

potential

use as a natural therapeutic agent in wound

treatment.

Determination of total flavonoids content

Calibration

curve

measurements

obtained

absorbance at a concentration of 2 ppm of

0.02732;

4

ppm

of

0.06026;

6

ppm

of

0.07144; 8 ppm of 0.10358; and 10 ppm of

0.1336.

These

results

obtained

a

linear

regression

equation

𝑦

=

0.0256

𝑥

+

0.0024

with

a

correlation

coefficient

value

of

𝑅

²

=

0.9824.

The determination of total flavonoid

content showed that the durian peel extract

at

a

concentration

of

1000

ppm

produced

an

absorbance

value

of

0.19458

with

a

flavonoid

content

of

7.5072

%

w/w

QE

(Quercetin Equivalent). This result indicates

that

durian

peel

extract

contains

a

moderate

level

of

flavonoid

compounds.

Flavonoids

are

well

known

as

important

bioactive

compounds

that

contribute

to

antioxidant activity, which plays a significant

role in protecting cells from oxidative stress.

160

NCA Susanto et al.,

Chempublish Journal, 10(1) 2026, 154-170

The presence of flavonoids in plant extracts

is

often

associated

with

their

ability

to

scavenge

free

radicals

and

enhance

tissue

repair processes during wound healing.

Several

studies

have

reported

that

durian

peel

contains

phenolic

and

flavonoid

compounds

that

contribute

to

its

antioxidant

properties.

also showed that plant extracts with higher

flavonoid content generally exhibit stronger

antioxidant

activity

and

better

biological

activity

in

wound

healing

applications.

Although the flavonoid content obtained in

this study

can

be

categorized

as

moderate

compared

to

some

medicinal

plants

with

higher

phenolic

levels,

it

still

indicates

that

durian

peel

has

promising

biological

activity.

Variations

in

flavonoid

levels

may

occur

due

to

differences

in

extraction

methods,

solvent

type,

plant

maturity,

and

environmental conditions.

The

presence

of

flavonoids

in

durian

peel

extract suggests its potential application as

a

natural

antioxidant

source

in

pharmaceutical and biomedical fields. In the

context

of

wound

healing,

flavonoids

can

promote

tissue

regeneration

by

reducing

oxidative

stress,

stimulating

fibroblast

proliferation,

and

enhancing

collagen

synthesis.

Therefore,

the

flavonoid

content

detected in durian peel extract supports its

potential

development

as

an

active

ingredient

in

topical

formulations

such

as

liposome-based

transdermal

patches

for

wound treatment.

Optimization,

evaluation

and

characterization of liposome

The

running

result

obtained

are

as

in

the

table

3.

Formula

optimization

was

performed using the

simplex lattice design

method.

This

method

was

chosen

because

it

requires

fewer

experiments,

and

minimizing

material

usage.

The

simplex

lattice

design

method

can

optimize

the

formula

for

various

different

amounts

of

material

composition,

with

the

total

being

kept

the

same

[16].

The

test

results

show

that the two variables indicate a significant

response (P<0.5) to the optimal antioxidant

and

EE

values

obtained

in

Table

4.

The

prediction

of

the

optimal

formula

for

this

liposome preparation was performed using

Design

Expert

version

13

software

with

Simplex

Lattice

Design.

Based

on

the

analysis

of

the

software,

the

desirability

value of the predicted optimal formula can

be

seen

in

Table

5.

The

desirability

value

indicates the achievement of a model used

against

the

expected

target,

with

a

value

ranging

from

0

to

1.

The

closer

the

desirability

value

is

to

one,

the

more

optimal

the

result.

From

the

experimental

results,

a

desirability

value

of

1.000

was

obtained

with

a

cholesterol

to

phosphatidylserine

ratio

of

5:1.

Table 3.

Results of running the simplex lattice design method

Std	Run	Cholesterol	Phosphatidylserine
5	1	20	40
4	2	40	20
1	3	50	10
3	4	30	30
2	5	10	50

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NCA Susanto et al.,

Chempublish Journal, 10(1) 2026, 154-170

Table

4.

Results

of

the

anova

simplex

lattice

design

on

the

results

of

the

formula

experiment

The results of ANOVA	Fit statistic
Parameter	p-Value	Significance	R 2	Adjusted	adjusted	Adeq Precision
Antioxidant	<0.0001	Significant	0.9999	0.9998	N/A	252.2996
EE	<0.0001	Significant	0.9993	0.9991	N/A	184.6367

The

results

of

the

liposome

antioxidant

activity

test

(can

be

seen

in

Table

5)

show

different

values

for

each

formula.

The

addition

of

cholesterol

at

a

certain

concentration

can

increase

the

encapsulation

efficiency

of

active

substances

and

reduce

leakage

in

the

liposome

bilayer

membrane

so

that

the

bioavailability

of

antioxidants

also

increases.

In

addition,

formulating

extracts

in liposome preparations can increase their

antioxidant

activity

because

the

liposome

properties

tend

to

be

stable

so

that

the

encapsulated

active

substances

can

be

optimally

targeted

[19].

Based

on

the

cholesterol

content

of

each

formula,

formula 5:1 was obtained with the strongest

antioxidant at a cholesterol level of 83.33%.

The

comparison

used

was

ascorbic

acid

solution

with

an

value

of

13.14

ppm

and

durian

fruit

peel

extract

produced

an

value of 115.57 ppm, because ascorbic

acid is able to donate hydrogen atoms and

react preferentially with radicals to produce

ascorbyl

free

radicals

which

are

relatively

more stable

[20].

Table 5.

Formula recommendations based on

Design Expert

software

No	Cholesterol	Phosphatidylserine	Antioxidant	EE	Desirability
1	50	10	57,3	86.8897	1,000

Table

6.

Evaluation

of

organoleptic,

pH,

IC

50

,

particle

size

analyzer,

polydispersity

index,

and

entrapment efficiency

Formulas

Evaluation Test

Organoleptic

pH

IC

₅₀

(μg/mL)

Size (nm)

PDI

EE (%)

F1

Liquid, yellowish-white color,

characteristic odor of

phosphatidylserine

7.49

59.59

218.7

0.381

68.624

F2

Liquid, yellowish-white color,

characteristic odor of

7.15

108.89

216.1

0.178

58.469

162

NCA Susanto et al.,

Chempublish Journal, 10(1) 2026, 154-170

Formulas

Evaluation Test

Organoleptic

pH

IC

₅₀

(μg/mL)

Size (nm)

PDI

EE (%)

phosphatidylserine

F3

Liquid, yellowish-white color,

characteristic odor of

phosphatidylserine

7.10

58.52

223.9

0.389

76.082

F4

Liquid, yellowish-white color,

characteristic odor of

phosphatidylserine

7.24

112.49

217.6

0.165

30.206

F5

Liquid, yellowish-white color,

characteristic odor of

phosphatidylserine

7.41

57.30

224.9

0.390

86.754

The

prepared

liposomes

exhibited

a milky-

white

appearance

with

a

slight

yellowish

tint,

a

liquid

consistency,

and

a

characteristic

odor

of

phosphatidylserine

powder,

consistent

with

[14].

As

presented

in

Table

6,

the

particle

size

of

all

formulations

ranged

within

the

Large

Unilamellar

Vesicles

(LUVs)

category

(100–1000

nm).

Liposomes

with

particle

sizes

between

100

and

300

nm

are

considered

particularly

suitable

for

cosmetic

applications

and

topical

drug

delivery

systems

because

they

facilitate

enhanced

skin

penetration

while

maintaining

formulation

stability.

Among

the

formulations,

Formula

3

exhibited

the

lowest polydispersity index (PDI), indicating

the

most

homogeneous

particle

size

distribution.

A

PDI

value

approaching

0

reflects

a narrow

and

uniform

particle

size

distribution,

whereas

values

greater

than

0.7

indicate

a

highly

heterogeneous

population

of

vesicles

[16].

A

low

PDI

is

desirable

because

it

contributes

to

improved

physical

stability,

reproducibility,

and predictable drug release behavior. The

entrapment efficiency (EE) of the liposomal

formulations

ranged

from

30.206%

to

86.754%,

with

Formula

5

exhibiting

the

highest

EE.

The

increased

entrapment

efficiency

observed

in

Formula

5

is

attributed to its higher cholesterol content.

Cholesterol

enhances

the

rigidity

and

stability

of

the

phospholipid

bilayer

by

reducing

membrane

fluidity

and

permeability,

thereby

minimizing

encapsulated

compound

leakage

and

improving

drug

retention

within

the

liposomal

vesicles

[7].

These

findings

demonstrate that cholesterol concentration

plays

a

critical

role

in

determining

the

encapsulation

performance

and

stability

of

liposomal formulations.

Evaluation of patch transdermal

Evaluation

of

patch

transdermal

showed

solid

texture,

colorless,

and

odorless

(PF0)

and

solid

texture,

brown

color,

and

distinctive

smell

of

ethanol

(PF1,

PF2,

PF3,

PF4,

PF5).

The

test

results

in

the

pH

test

obtained a pH ranging from 4.75-7 so that it

still

meets

the

safe

pH

for

topical

use

because

the

range

is

between

4-7.

Dose

uniformity

is

very

important

in

this

preparation,

where

the

patch

weight

must

163

NCA Susanto et al.,

Chempublish Journal, 10(1) 2026, 154-170

be

and

the

Coefficient

of

Variation

(CV)

value

must

meet

the

requirements

<5%.

Based

on

table

7. shows

that

the

CV value

produced

has

met

the

requirements.

The

thickness of the patch should not be more

than 1 mm, if the patch is too thick it will be

difficult

to

release

the

active

substance

from

the

patch

and

the

results

obtained

have

met

the

requirements.

The

folding

resistance

of

the

patch

is

found

that

the

number

of

folding

resistance

has

met

the

requirements,

which

is

>300.

The

humidity

of the patch preparation has a requirement

of

<10%

and

generally

2-10%.

Based

on

table

7.

shows

that

humidity

ranges

from

5,7-10%.

The

stability

of

the

patch

formula

is obtained with a preparation with a shape,

texture

and

color

that

does

not

change

during

treatment

so

that

the

formulation

exhibited

good

stability

test

[17].

Table

7.

Organoleptic

test,

pH,

weight

uniformity,

thickness,

folding

resistance,

moisture

content,

stability test

Formula

Evaluation Test

Organoleptic

pH

Weight

uniformity

(%)

Thickness

(mm)

Folding

resistance

Moisture

content (%)

Stability

PF0

Solid,

colorless, and

odorless

4.75

4.55

0.45

>400

5.7

No change in

color, odor, and

consistency

PF1

Solid, brown

color,

characteristic

odor of

ethanol

5.9

3.54

0.36

>400

6

No change in

color, odor, and

consistency

PF2

Solid, brown

color,

characteristic

odor of

ethanol

6.1

3.15

0.35

>400

6,9

No change in

color, odor, and

consistency

PF3

Solid, brown

color,

characteristic

odor of

ethanol

6.71

2.25

0.28

>600

8,2

No change in

color, odor, and

consistency

PF4

Solid, brown

color,

characteristic

odor of

ethanol

6.4

2.85

0.32

>600

7,1

No change in

color, odor, and

consistency

PF5

Solid, brown

color,

7.0

2.44

0.31

>600

9.8

No change in

color, odor, and

164

NCA Susanto et al.,

Chempublish Journal, 10(1) 2026, 154-170

Formula

Evaluation Test

Organoleptic

pH

Weight

uniformity

(%)

Thickness

(mm)

Folding

resistance

Moisture

content (%)

Stability

characteristic

odor of

ethanol

consistency

The

FTIR

characterization

results

(Figure

1)

showed a shift in the O–H functional group

between

the

cholesterol

and

extract

samples after the formation of the liposome

preparation.

The

O–H

stretching

vibration

was

observed

at

approximately

3200–3600

cm

⁻

¹,

and

the

absorption

band

became

broader,

indicating

hydrogen

bonding

interactions

between

the

components

in

the

liposome

system.

This

phenomenon

may

occur

due

to

interactions

between

molecules

containing

polar

functional

groups, such as hydroxyl (–OH) groups from

phenolic

compounds

in

the

extract

and

polar

groups

present

in

phospholipids,

which

can

form

hydrogen

bonding

interactions.

Figure 1.

FTIR characterization results of liposomes

The

FTIR

characterization

showed

several

shifts

in

functional

groups

after

the

formation of the liposome system. The N–H

stretching

vibration

was

observed

in

the

region

of

approximately

3300–3500

cm

⁻

¹,

which

may

originate

from

the

interaction

between polar groups present in the extract

and

the

phospholipid

components.

These

shifts may occur due

to hydrogen bonding

interactions

among

cholesterol,

phosphatidylserine,

and

the

bioactive

compounds contained in the extract.

Furthermore,

the

C–H

stretching

vibration

observed at approximately 2850–2950 cm

⁻

¹

showed changes after the formation of the

165

NCA Susanto et al.,

Chempublish Journal, 10(1) 2026, 154-170

liposome system. These changes may occur

due

to

interactions

with

other

functional

groups

present

in

the

extract,

such

as

hydroxyl

(–OH)

groups

from

phenolic

compounds

and

flavonoids,

which

can

affect

intermolecular

interactions

and

binding

strength

within

the

liposome

structure [21].

Wound healing activity of liposome patch

All

experimental

procedures

involving

rats

were

approved

by

the

Research

Ethics

Committee

of

RSUD

Dr.

Moewardi

(No.

1.475/VI/HREC/2024). Male Wistar rats were

anesthetized

with

lidocaine

to

reduce

pain

caused

by

the

incision,

as

it

may

induce

muscle

relaxation.

Wound

diameter

measurements were taken every three days

until the wound diameter approached zero.

The

wound

drying

process

was

characterized by the absence of edema and

bleeding, the formation of scabs on the skin

as an indicator of the healing process, and

the

gradual

reduction

of

wound

size.

The

statistical

test

results

showed

a

significant

difference (p < 0.05) between the treatment

groups in the observation of wound healing

days (Table 8).

Table 8.

Wound diameter result in rats.

Groups

Percentage of wound diameter in rats (%)

1

4

7

Positive Control

25.00 ± 0.00

50.00 ± 0.00

75.00 ± 0.00

Negative Control

22.50 ± 0.00

27.50 ± 0.00

32.50 ± 0.00

Liposome patch 1

22.50 ± 0.00

30.00 ± 0.00

65.00 ± 0.00

Liposome patch 2

22.50 ± 0.00

30.00 ± 0.00

60.00 ± 0.00

Liposome patch 3

22.50 ± 0.00

32.50 ± 0.00

70.00 ± 0.00

Liposome patch 4

22.50 ± 0.00

27.50 ± 0.00

52.50 ± 0.00

Liposome patch 5

22.50 ± 0.00

32.50 ± 0.00

72.50 ± 0.00

The

in

vivo

evaluation

of

the

patch

preparations demonstrated gradual wound

closure in the rat test animals (Table 9). On

day

1,

all

groups

showed

similar

incision

wounds characterized by redness and slight

swelling around the wound area. By day 4,

scab

formation

began

to

appear

in

most

treatment

groups,

indicating

the

initiation

of the

wound healing process. The healing

process

was

characterized

by

the

absence

of

edema

and

bleeding,

the

formation

of

scabs

on

the

wound

surface,

and

the

gradual

reduction

of

wound

diameter.

By

day 7, the wound area in several treatment

groups

had

significantly

decreased,

indicating

progressive

tissue

regeneration.

Among

the

treatment

groups,

the

PF5

liposome

patch

group

showed

the

highest

166

NCA Susanto et al.,

Chempublish Journal, 10(1) 2026, 154-170

percentage

of

wound

healing

(72.5%)

on

day

7,

indicating

better

healing

activity

compared

to

the

other

liposome

formulations.

The

order

of

wound

healing

effectiveness from the fastest to the slowest

was

povidone

iodine

plaster

(positive

control),

PF1,

PF2,

PF3,

PF4,

and

the

negative

control

group.

These

results

suggest

that

liposome-based

patch

formulations

contributed

to

accelerating

the wound healing process

Table 9.

Visualize of wound diameter result in rats.

Formula

Day 0

Day 3

Day 7

+

-

Liposom patch 1

Liposom patch 2

Liposom patch 3

Liposom patch 4

Liposom patch 5

167

NCA Susanto et al.,

Chempublish Journal, 10(1) 2026, 154-170

The

accelerated

wound

healing

effect

may

be associated with the presence of bioactive

compounds

in

durian

peel

extract,

particularly flavonoids, which exhibit strong

antioxidant

activity.

Flavonoids

play

an

important

role

in

reducing

oxidative

stress

by

inhibiting

the

formation

of

reactive

oxygen

species

(ROS),

scavenging

existing

ROS,

and

enhancing

the

activity

of

endogenous

antioxidant

defense

systems.

The reduction of ROS levels is important in

promoting effective wound healing because

excessive

oxidative

stress

can

delay

tissue

regeneration.

In addition, the incorporation of durian peel

extract into a liposome delivery system may

further

enhance

the

therapeutic

effect.

Liposomes

can

stabilize

therapeutic

compounds,

facilitate

penetration

through

biological

membranes,

and

improve

tissue

uptake

and

biodistribution

of

bioactive

compounds

in

vivo.

The

presence

of

other

active

compounds

in

durian

peel,

such

as

alkaloids and saponins, may also contribute

synergistically

to

antimicrobial

and

tissue

repair activities. Overall, the wound healing

process

observed

in

this

study

was

characterized by the absence of edema and

bleeding, the appearance of scabs on day 4,

and significant wound closure by day 7 [22].

Faster wound closure is beneficial because

it

reduces

the

risk

of

infection

and

promotes

more

efficient

tissue

regeneration. These findings are supported

by

the

antioxidant

activity

test

of

the

liposome

preparations,

which

showed

moderate

to

strong

antioxidant

activity,

further supporting their role in accelerating

the wound healing process [22].

Conclusions

Based on the results of the study it can be

concluded

that,

durian

fruit

peel

extract

liposomes

(Durio

zibethinus

Murr.)

can

be

formulated as a patch using a combination

of

HPMC

and

EC

as

the

polymer.

The

resulting

liposome

preparation

underwent

several

physical

evaluation

tests

and

showed

results

that

met

the

required

standards,

particularly

in

the

stability

test,

as no changes in shape, color, or odor were

observed. In addition, the patch preparation

also

underwent

several

physical

evaluation

tests, including weight uniformity, thickness,

folding

resistance,

pH,

moisture

content,

and

cycling

tests

to

determine

patch

stability.

The

results

of

these

evaluations

indicated

that

the

patch

formulations

met

the

required

criteria.

Furthermore,

the

prepared

patches

demonstrated

therapeutic effects in the healing of incision

wounds

in

male

Wistar

rats

(Rattus

norvegicus

L.),

with

a

wound

healing

percentage of 72.5% on day 7. The healing

process

was

characterized

by

the

absence

of

edema

and

bleeding,

the

formation

of

scabs,

hair

regrowth

around

the

wound

area, and gradual wound closure.

Acknowledgement

This

research

supported

by

RKAT

PTNBH

Universitas

Sebelas

Maret

for

the

2025

Fiscal

Year

through

he

Research

Grant

Scheme

HGR-UNS

with

Agreement

Letter

Number: 371/UN27.22/PT.01.03/2025.

Author Contributions

Conceptualization,

NCAS;

Methodology,

NCAS;

Formal

Analysis,

NCAS;

MEP;

Investigation,

MEP;

Resources,

DTU;

Data

Curation,

NCAS;

MEP

and

DTU;

Writing

–

Original

Draft

Preparation,

NCAS;

MEP

and

DTU; Writing – Review & Editing, NCAS; MEP

and

DTU;

Visualization,

NCAS;

MEP

and

DTU.

All

authors

have

read

and

agreed

to

the published version of the manuscript

Conflict of Interest

The authors declare no conflict of interest

.

168

NCA Susanto et al.,

Chempublish Journal, 10(1) 2026, 154-170

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Characterization and In Vivo Evaluation of Durian Peel Extract in Nanoliposome Transdermal Patch for Wound Healing

Nindita Clourisa Amaris Susanto 1 * , Milkazia Elda Putri 1 , Dayinta Tyas Utami 1 ,

D ian Eka Ermawati 1 , Heru Sasongko 1 , Sholichah Rohmani 1 Anif Nur Artanti 1 , Diyah Tri Utami 1 , M. Fiqri Zulpadly Mh 1 , Ulfa Afrinurfadhilah Darojati 1 , Annisa Diyan Meitasari 1 , Meta Kartika Untari 1 , Alifina Izza 2

A bstract

Graphical Abstract

Introduction

Characterization and In Vivo Evaluation of Durian Peel Extract in

Nanoliposome Transdermal Patch for Wound Healing

Nindita Clourisa Amaris Susanto

1

*

,

Milkazia Elda Putri

1

,

Dayinta Tyas Utami

1

,

D

ian Eka Ermawati

1

, Heru Sasongko

1

, Sholichah Rohmani

1

Anif Nur Artanti

1

, Diyah Tri

Utami

1

, M. Fiqri Zulpadly Mh

1

, Ulfa Afrinurfadhilah Darojati

1

,

Annisa Diyan Meitasari

1

,

Meta Kartika Untari

1

,

Alifina Izza

2

A

bstract