preparation and characterization of mpeg-pcl based...

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Palma Journal

Preparation and Characterization of mPEG-PCL based

Biodegradable Polymeric Nanoparticles for Anticancer

Drugs Delivery

Samira Zaree, MSc in Applied Chemistry, Faculty of Applied Chemistry, Islamic Azad

University Shahr Ray Branch

Kobra Rostamizadeh MSc in Applied Chemistry, Faculty of Applied Chemistry, Islamic Azad

University Shahr Ray Branch

Abstract This research has aimed at synthesizing mPEG-PCL copolymers and using their nanoparticles for drug

delivery of anticancer drug called Tamoxifen. Tamoxifen Citrate is a highly lipophilic drug with a poor

solubility in water. Tamoxifen Citrate is used to against breast cancer also for infertility treatment. In

this research, mPEG-PCL copolymer was synthesized using ring opening polymerization of ε-

caprolactone in presence of mPEG as initiator and Sn(oct)2 as catalyzer at temperature of 160°C.

HNMR1, GPC, ATIR, and DSC analyses were used to prove synthesis of copolymer. The ATIR spectrum

of mPEG-PCL copolymer indicates a sharp and intense absorption bond within 1722cm-1 frequency

related to carbonyl groups (C=O) and an intense peak in 2963cm-1 that shows ethylene groups of PEG

that verifies copolymer synthesis. HNMR1 spectrum of copolymer also indicates the peak related to

PEG methyl group in area of 3.66ppm and 1.4ppm, 1.60ppm, and 4.2 peaks that are related to –(CH2)3-

, -OCCH2-, and –CH2OOC- groups of caprolactone, respectively that is another reason for successful

synthesis of copolymer. HNMR1 spectrum was used to calculate numerical molecular mass of polymer.

Thermal properties of copolymer were examined using DSC and results showed that melting point of

copolymer is 68.58°C. Amphiphilic polymer nanoparticles of mPEG-PLC consisting of Tamoxifen were

prepared using O/W emulsion. Size of nanoparticles was measured using DLS method and this size

obtained to 151nm. Efficiency of drug loading in nanoparticles and drug release profile in In vitro

environment were measured using UV spectroscopy. The results indicated that efficiency of loaded and

encapsulated drug was obtained to 12% and 72%, respectively indicating high drug loading in

nanoparticles. The data obtained from drug release from nanoparticles in different environments

showed that the drug is released under the control over a long-term time from nanoparticles. In general,

it can be concluded that mPEG-PCL nanoparticles consisting of drug can be a good option for

controlled release of Tamoxifen in cancer treatment.

Keywords: Nanoparticles, mPEG-PCL, Tamoxifen, Controlled Drug Delivery

Introduction

Pharmaceutical Science is indeed the application of biological and chemical principles to control and

transfer the drug into a specific space in a living environment based on medical and therapeutic goals,

because when we use a drug only a small of that reaches to action sites and a big part of drug is lost through

accumulation in non-target tissues due to rapid removal from the body before reaching to the target point.

Drug can have a therapeutic role if it is protected until it reaches to target point in body having its chemical

and biological properties. Some of drugs are highly toxic and might cause negative side effects or their

therapeutic effects might be reduced if they are destroyed during release [1]. Therefore, the goal of

researchers who investigate in this field is to find solutions in which, therapeutic effect of drug is maximized

and side effects are minimized. Over the recent years, modern drug delivery systems such as Nano-drugs

have been highly considered to treat diseases. To deliver a proper dose of drug to target site and to prevent

from side effects of drugs, pharmaceutical world needs appropriate formulations and carriers. In this regard,

Colloidal carriers such as liposomes, micelles, and nanoparticles should be used in appropriate methods in

order to achieve the mentioned goal. It has been known that those drug delivery systems that are designed

Pal. Jour. V.16, I.3, 2017, 53-64

Copyright © 2017 by Palma Journal, All Rights Reserved

54 S.Zaree and K.Rostamizadeh

based on nanoparticles will have greater therapeutic effects, lesser toxicity, more acceptance level among

patients, and better accumulation of drug in target site of body [1-2]. Nowadays, nanoparticles are broadly

using as transdermal, as a carrier of antimicrobial and anti-cancer agents, carrier of peptides and proteins

such as insulin and carriers of anti-inflammatory and respiratory drugs [3]. Biodegradability is enzymatic

hydrolysis or non-enzymatic hydrolysis of polymers to soluble or insoluble in water. Biodegradability

consists of two complementary processes of degradation and erosion. In degradation process, molecular

volume of polymers will be decreased while erosion mechanism includes physical phenomena such as

dissolution and release of a fraction of molecular weight of the polymer matrix. Degradation products are

removed from the body through a natural metabolic path [4]. Nanoparticles, in particular polymeric

nanoparticles, have been broadly considered as pharmaceutical systems. These Colloidal carriers have some

advantages such as drug protection against degradation, purposeful transfer of drug to sites and tissues,

transferability of proteins, drugs and oligonucleotides. These nanoparticles also indicate some unique

properties such as controlling biological distribution of drug and its release pattern after injection. Such

property would improve therapeutic effect of a drug and reduce toxicity and side effects of it [5]. A wide

range of drugs can be proposed using carrier nanoparticles. Nanoparticle can be used to provide hydrophilic

drugs, hydrophobic drugs, proteins, vaccines, and biological macromolecules [6, 7, 8, 9].

Research Background Shaobing Zhou et al. [10] prepared PCL-PEG poly copolymer from epsilon-PEG and poly-PCL using

stannous octoate as catalyst at 160 degrees; they also examined effect of molecular weight of PEG and ratio

of PCL/PEG on copolymer. PCL-microspheres and PEG-PCL copolymers containing HAS were prepared

using double W/O/W emulsion based on the solvent extraction. According to their results, loading

efficiency of HAS in PECL-microspheres is higher than PCL microspheres. Xintao Shuai et al. [11]

synthesized diblock copolymers of poly (epsilon-caprolactone) (PCL) with various compositions then

prepared micelles of amphiphilic block copolymers self-assembled into nanoscopic and encapsulated

doxorubicin (DOX) in its hydrophobic cores. It was determined that micelles have core-shell structure and

size of 100nm. The longer the PCL chain, the more percent of encapsulated drug in micelles and the larger

the size of micelles will be. Triblock copolymer of PCL-PEG-PCL was synthesized using ring-opening

polymerization at 120°C during 24h by Keng-Lun Chang et al. [12] then nanoparticles of this copolymer

was used as lauric acid carrier against Acne Vulgaris. Size of prepared nanoparticles obtained to 24-89nm.

mPEM-PCL copolymer was synthesized by Wichuda Nanthakasri et al. [13] using methoxy poly (ethylene

glycol) and poly(caprolactone), and Sn(Oct)2 catalyzer and these nanoparticles were prepared using nano-

precipitation method without any surfactants. According to TEM analysis, nanoparticles were spherical

with smooth surface. Average size of the blend nanoparticles obtained from light-scattering analysis slightly

decreased with increase in blend ratio of MPEG-b-PCL. Maling Gou et al. [14] prepared nanoparticles of

triblock copolymer PCL-PEG-PCL blank successfully using solvent evaporation method without using

catalyst and benefitted from it for drug delivery of Han Kewell Drug. The size of obtained particles was

smaller than 200nm and increase in concentration of polymer in O/W resulted in increased size of particles.

Xia Wei Wei [15] introduced chemical synthesis methods of PCL/PEG diblock copolymers and triblock

PEG-PCL-PEG and PCL-PEG-PCl copolymers, synthesis methods of micro-nanoparticles, PCL-PEG

hydrogels, PCL-PEG and their physic-chemical properties of them for drug delivery. Also, they studied

principles of each effective method and parameters in preparing their nanoparticles and copolymers.

Longhai Piao et al. [16] synthesized different triblock PCL-PEG-PCL copolymers using ring-opening

polymerization from PCL with different molecular weights in presence of PWG using Ammoniate calcium

catalyst at 60°C degrees in Xylene solution and micelles of considered copolymer was prepared using

double W/O/W emulsion method. They showed that micelles of PCL-PEG-PCL have core-shell structure

in which, PCL forms core and PEG forms shell. Jae-Gon Ryu et al. [11] synthesized triblock PCL-PEG-

PCL copolymer without using catalyst with various molecular weight changing in PEG-PCL ratio and

prepared nanoparticles of core-shell type PCL-PEG-PCL using dialysis method then loaded clonazepam

drug in nanoparticle and examined effect of various solvents when preparing nanoparticles. The obtained

results indicated that use of 1.4 dioxin solvent would lead to formation of nanoparticles with smaller sizes

Preparation and Characterization … 55

and greater loading through accelerated drug release. Increase in molecular weight of polymer would lead

to increase in loading efficiency.

Applied Chemical Materials Stannous 2-ethyl-hexanoate [Sn(Oct)2], Dichloromethane, petroleum ether, chloroform, ethanol, methanol,

acetone, ε-Caprolactone, methoxy polyethylene glycol (MW = 5000), Tetrahydrofuran, methoxy

polyethylene oxide, calcium hydride, and polyvinyl alcohol (PVA) were the chemical materials with high

purity prepared from Merck and Sigma companies. Also, Tamoxifen Citrate was purchased from Iran

Hormone Company. To prepare buffer, sodium chloride, calcium chloride, sodium hydrogen phosphate,

potassium dihydrogen phosphate (Merck) were used.

Devices

The scale model D225 Satorius with five decimal integers was used to weight samples. In this project,

Rotary Heidolph2 (Germany) was used for evaporation of solvents and Memmert vac-oven was used to dry

materials. To examine results of synthesis and obtaining considered product, FT-IR spectrum was recorded

using Brujer Tensor device model 27, HNMR1 was recorded using HNMR1 Device, 400mh Brucker in

deuterium containing chloroform solvent, D2O. To prepare nanoparticles, Homogenizer machine (Silent

Crusher M) made in Germany was used. Size and surface potential of synthesis nano-carriers was examined

using DLS (Dynamic Light Scattering) device with Malvern Zetasizer Nano ZS 90 model. For constant and

continuous mix of drug during release, a shaker with model Heidolph Titramax1000 was used.

Synthesis of mPEG-PCL copolymer

mPEG-PCL copolymer was synthesized using ring-opening of polymerization of waterless monomer PCL

in presence of dried methoxy polyethylene glycol as initiator and catalyst of Sn octane (reaction 1) [13, 17].

3g of mPEG (MW=5000) was poured into a balloon to be dried under the vacuum and 80°C for 24h. 6g

monomer PCL was poured into a balloon and as kept for one week in hydride calcium to dry it then it was

filtered using Buchner funnel and vacuum pump. mPEG and PCL poured into a balloon and 0.01mm of

Sn(oct)2 catalyst was added to the balloon per 1mm of mPEG hydroxyl. Then, vacuum balloon was kept in

oil bath. Temperature of reaction was reached to 150°C under the nitrogen atmosphere, magnetic mixture

continuing the reaction for 12h then the system was cooling, and copolymer was solved into chloroform to

be deposited in cold diethyl ether. The obtained deposit was collected by filtering paper then was dried.

Figure 1. Synthesis path of mPEG-PCL copolymer

Analysis of mPEG-PCL Copolymers

HNMR11 Spectroscopy

To determine structure of mPEG-PCl copolymer, HNMR1 was employed. HNMR1 spectrums were captured

using 400MHz Bruker device at 25°C temperature. Deuterochloroform (CDCL3) and Trimethylsilyl (TMS)

were used as solvent and internal standard, respectively. The captured spectrums in (CDCL3) were used to

determine numerical molecular mass of synthesized copolymers using integration of the area under the

peaks corresponding to different chemical groups. The ratio of lactone to ethylene glycol in synthesis

copolymer can be calculated using equation 1.

Ie

Ia

Ie

Ia

EOPCL 33.1

4

3:

1 Nuclear Magnetic Resonance Spectroscopy


Where, Ia in integration of the area under the peak of methyl corresponding to PCL that is appeared within

1.5-1.6ppm of spectrum and Ie in integration of the area under the peak of methylene group of PEH that is

observed within 3.6-3.7ppm. Obtaining the ratio of PCL/EO in synthesized copolymer, degree of PCL

polymerization is calculated regarding polymerization degree of initial PEG based of equation 2 and finally

molecular mass of copolymer is obtained using equation 3. EOPCLDPDP PEGPCL /

)()()( EOWPEGPCLWPCLPCLmPEGn MDPMDPM

Tamoxifen Measurement

To measure Tamoxifen, UV spectrophotometry method was used. To illustrate calibration of curve, 2mg/ml

Tamoxifen solution in methanol was prepared then some solutions with different concentrations (from 6.25

to 75µg/ml) were prepared; adsorption of each of samples was measured using UV spectrophotometry

(JENWAY, UK) within wavelength of 𝜆=250nm then adsorption-concentration chart of Tamoxifen was

illustrated.

Preparation of mPEG-PCL Copolymer Nanoparticle through O/W Emulsion

To prepare nanoparticles, 10mg Tamoxifen and 50mg mPEG-PCL copolymer was solved in 10ml

Dichloromethane and this solution was added to 50ml deionized water containing 0.25 W.V% poly(Vinyl

alcohol) under the mixture of 2000rpm. Dichloromethane will be evaporated under the mixture of 180rpm

for during 24h then nanoparticles are collected by 14000rpm centrifuge and washed through deionized

water.

Results and Discussion

In this research, mPEG-PCL polymer was synthesized in laboratory first and then the loaded nanoparticles

with Tamoxifen drug were prepared by emulsion method then size and properties of them were examined.

Finally, drug release from nanoparticles was tested in different PHs.

Synthesis and Identification of mPEG-PCL Copolymers

Radical ring-opening method was used to synthesize mPEG-PCL copolymer (figure 1). Structure and

composition of synthesized copolymer was determined by HNMR1 spectroscopy in CDCL3 solvent,

differential scanning calorimeter (DSC), FT-IR spectroscopy, and GPC.

Figure 2: Synthesis path of mPEG-PCL copolymer

HNMR1 Spectra of mPEG-PCL Copolymer

Figure 2 depicts chemical structure of PCL. According to structure of PCL and its HNMR1 spectra, the

multiple peaks at the area of 1.7-1.8ppm are related to b, c, and d protons. Also, multiple peak in 4.1ppm is

determinant of proton a and peak of 2.5ppm corresponds to proton e.

O

O

a

bc

d

e

Figure 3: Chemical structure of Ɛ-PCL


After testing raw material using on synthesis for verification of copolymer synthesis, structure and

composition of synthesized copolymer by HNMR1 spectroscopy in solvent CDCL3, which is indicated in

figure 3, was studied. As can be seen, the existing peak at 3.38 and 3.64 areas corresponds to methoxy

group and methyl PEG groups. Peaks of 1.3 ppm (2H,g), 1.6 ppm (4H,f), 2.2 ppm (2H,e), 4.06 ppm (2H,h),

and 3.4 ppm (3H, a) are related to –(CH2)3–, (-(CH2)2-OCCH2-), and (-CH2OOC-) PCL groups,

respectively. The calculated weighting molecular mass of HNMR1 obtained to 21000g/mol.

Figure 4: HNMR1 spectra of mPEG-PCL copolymer

DSC (differential scanning calorimeter) Spectra of mPEG-PCl Copolymer

Thermal analysis can be defined as measurement of properties of a polymeric sample against temperature

changes. The most important factor in study of polymers is measurement and assessment of their thermal

sustainability. Usually, decreased weight is used to measure thermal sustainability. Weigh changes against

increased thermal degree or against increased time is recorder under constant heat degree. Differential

scanning calorimeter is a method in which, difference between thermal energy entering to the sample and

reference material is measured as a function of thermal degree. The relevant DSC to mPEG-PCL copolymer

in figure 4 show that the peak obtained from sample is at range of 58.68°C that is an endothermic peak.

Previous studies have indicated that PEG and PCL homo-polymers, which are both as semi-crystalline

polymers, have melting point of 62°C and 60°C, respectively. Accordingly, thermal trend in copolymer

spectra is belonged to melting point of PEG and PCL. Moreover, heating peak occurs at 39.1°C in obtained

spectra that can be attributed to temperature f crystallization of PEG.


Figure 5: DSC spectra of mPEG-PCL copolymer

GPC Spectra Related to mPEG-PCL Copolymer

Molecular mass of weighted average and distribution of molecular mass of mPEG-PL copolymer is

examined by analysis of chromatography gel. The sample is solved in tetrahydrofuran then molecular and

poly-dispersity mass and of synthesized copolymer is calculated after injecting to the column and

comparing with calibration chart using illustrated standard polystyrene. The chart of molecular mass is

depicted in figure 5 that shows a peak at 7.25 second after loading. After inserting this time into the Excel

chart related to mPEG=5000g/mol, weighting molecular mass is equal to 23652g/mol.

Figure 6: GOC spectra of mPEG-PCL copolymer

Preparation of Co-polymeric Micelles through O/W Emulsion

mPEG-PCL nanoparticles are prepared using O/W emulsion method. This method is usually used to

encapsulate dissolved drugs in water with hydrophobic copolymers. Surfactant existing in this method

contributes to more sustainability of particles, smaller size, and non-aggregation of particles. Micelle-

shaped nanoparticles were prepared from mPEG-PCL copolymers using O/W emulsion method. To prepare

micelles, organic solvent of dichloromethane was used. When amphiphilic copolymers are exposure to

specific solvents that solve a part of polymer, they are able to form micelle structures; therefore, amphiphilic

nature of mPEG-PCl copolymers with hydrophilic blocks of OEG and hydrophobic blocks of PCL would

enable them to shape micelle in water. In other words, when a polymeric solvent is added to the water drop

by drop, they will arrange micelle structures evaporating dichloromethane of mPEG-PCl copolymers so

that these structures are originated from their amphiphilic properties. Hydrophilic part of PEG copolymer

would create hydrophilic shell of micelle in water and hydrophobic part of PCL copolymer forms core of

micelles.

Analysis and Measurement of Size of Nanoparticles

At this step after preparing nanoparticles, size of prepared nanoparticles from considered DLS sample was

measured. According to the chart of nanoparticles size measurement (figure 6), average size of

nanoparticles obtained to 184.4nm with PDI=0.418 without drug loading.


Figure 7: Size of synthesized polymeric nanoparticles without drug loading, a) numerical-based, b) intensity-based

Average size of polymeric nanoparticles with drug loading was examined by the chart of particle size that

id depicted in figure 7. According to the chart of average size of nanoparticles, average size obtained to

151.7nm with PDI=0.328. Considering the size of nanoparticles without drug (184.4nm) loading, drug

loading has not created a significant change in size of nanoparticles that can be a reason for drug absorption

into nanoparticles.

Figure 8: Size range of nanoparticles loading by Tamoxifen drug a) numerical-based b) intensity-based

a)

b)

a)

b)


Analysis of Zeta Potential of Nanoparticles

The chart of average distribution of surface charge of polymeric nanoparticles without drug loading is

depicted n figure 8. The size of surface potential obtained to -5.04 in accordance with the distribution chart

of mentioned surface charge.

Figure 9: Zeta potential of polymeric nanoparticles without Metxifen loading

The chart of average distribution of surface charge of polymeric nanoparticles after drug loading is

illustrated in figure 9. Surface potential obtained to 13.9(mv) that has been increased in comparison with

zeta potential of polymeric nanoparticles without drug loading; this is another reason for drug adsorption

into polymeric nanoparticles and presence of mPEG in shell of nanoparticles.

Figure 10: Zeta potential of nanoparticles with Tamoxifen loading

Analysis of SEM of polymeric nanoparticles loaded by Tamoxifen drug

Morphology of nanoparticles was examined using SEM and relevant pictures are shown in figure 10. After

preparing nanoparticles that were loaded by Tamoxifen drug, SEM image was captured and this image is

shown in figure 10. SEM image indicates that spherical nanoparticles with almost same shapes had size of

234nm. As can be seen, the average size of nanoparticles in captured image is matched with the size

obtained from DLS.


Figure 11: SEM spectra of polymeric nanoparticles loaded by drug

FT-IR Spectra of mPEG-PCL polymeric nanoparticles loaded by Tamoxifen drug

According to structure of Tamoxifen Citrate (Figure 11) and its FT-IR spectra, absorption bonds in 1590cm-

1 and 1471cm-1 are related to aromatic ring of drug. Absorption bond within 2828cm-1 is attributed to

unsaturated stretching C-H group and absorption bond within 2960cm-1 is related to CH3 group. 1217cm-1

bond indicates stretching C-O group and 1300cm-1 bond indicates stretching C-N group. The existing bond

at area of 703cm-1 and substitution of Ortho and 3010cm-1 bond indicates stretching OH group (Figure 12).

Figure 12: Structure of Tamoxifen Citrate

Figure 13: FT-IR spectra of Tamoxifen Citrate

Comparing the spectra of loaded nanoparticles with spectra of mPEG-PCL copolymer and Tamoxifen

spectra, drug loading in nanoparticles was proved. Presence of bond in 1602cm-1 determinant of aromatic

ring was observed at both spectra of Tamoxifen and nanoparticles. 1728cm-1 bond at two spectra of

copolymer and nanoparticles indicates stretching carbonyl group. 1300cm-1 at two spectra of Tamoxifen

and nanoparticles determines stretching C-N group. Stretching C=O group in 1271cm-1 is seen at two

spectra of Tamoxifen and nanoparticles. Existence of bonds in 2868cm-1 and 2940cm-1 in spectra of

copolymer and nanoparticles is determinant of stretching methylene CH groups. The results obtained from

spectra (figure 13) showed that Tamoxifen drug has been loaded in polymeric nanoparticles.


Figure 14: FT-IR spectra of nanoparticles

DSC Spectra of Tamoxifen Citrate

The DSC relevant to Tamoxifen indicates that the peak obtained from sample is at the area of 145.43°C,

which is an endothermic peak and indicates melting point of Tomoxifen Citrate (Figure 14).

Figure 15: DSC spectra of Tamoxifen Citrate

Tamoxifen Measurement

Figure 15 depicts tamoxifen curve within maximum wavelength of 250nm. This figure shows linear

functionality of concentration of Tamoxifen and its absorption in organic medium. The linear equation

obtained from this figure has been used to estimate concentration of Tamoxifen in evaluation of drug

loading rate also in analysis of drug release.

Figure 16: Calibration curve of Tamoxifen citrate in 𝜆=250nm

Loading and Encapsulation Rate of Tamoxifen in Micelles of mPEG-PCL Copolymers Considering

Calibration Curve of Tamoxifen

According to following calculations, the amount of loaded and encapsulated drug obtained to 12.9096%

and 70.025%, respectively. The reason for drug loading in Tamoxifen in hydrophobic core of nanoparticles

(PCT part) is hydrophobic nature of this drug.


%EE =

According to following calculations, if sedimentation rate from loaded nanoparticles by Tomoxifen is

100%, the amount of loaded drug is about 16.66%.

%

According to the obtained results and similar theoretical and empirical percent of encapsulated drug in

nanoparticles, mPEG-PCL nanoparticles have high ability to encapsulate Tamoxifen.

Chart of Drug Release from Nanoparticles Synthesizing in Different PHs

Figure 16 shows release chart of Tomoxifen from mPEG-PCl nanoparticle in Phosphate buffer with

PH=7.40 containing Toin. Tomoxifen Citrate is a hydrophobic drug; hence, phosphate buffer containing of

0.01 (w/v) toin 80 was used to increase solubility of drug. As can be seen in figure, 9.82% of Tomoxifen

was released from nanoparticles within the first 72 hours.

Figure 17: Drug release from nanoparticles in PH=7.40 containing toin 80

According to figure 17, 13.72% of Tomoxifen was released from nanoparticles within the first 72 hours. It

will be found comparing these two figures that drug release in acidic environment is faster.

Figure 18: Drug release from nanoparticles in buffer with PH=5.40


Conclusion

In this research, mPEG-PCL copolymer with 1/3 ratio was synthesized then its structure and composition

was confirmed by HNMR1 and FT-IR. Thermal behavior of synthesized copolymer by DSC was examined

and then molecular mass of synthesized copolymer was determined by GPC. In spectra of FT-IR of mPEG-

PCL copolymer, a sharp and intense absorption bond was observed within 1722cm-1 frequency that

confirms presence of esteric carbonyl groups (C=O) indicating an intense peak in 2963cm-1 that is indicator

of OEG methylene groups so that it can confirm synthesis of copolymer. Results obtained from synthesis

of mPEG-PCL copolymer indicated that copolymer has been synthesized completely. The DSC related to

mPEG-PCL copolymer showed that peak obtained from sample is at the area of 68.58°C, which is an

endothermic peak and indicates melting point of PCL and PEG. The produced polymer was used to create

biodegradable nanoparticles based on poly ethylene glycol and poly caprolactone. Micelles of mPEG-PCl

copolymers were prepared by O/W emulsion method and Tomixifen was loaded in it. The size of particles

was equal to 151.7nm and zeta potential of particles was 13.9mv. Efficiency of drug loading in

nanoparticles and drug release profile were measured In vitro using UV spectroscopy. The obtained results

showed that efficiency of loaded and encapsulated drug are 12% and 70%, respectively, indicating high

drug loading in nanoparticles. The results obtained from drug release from nanoparticles indicated that drug

is released from nanoparticles through a controlled method during a long-term period. In conclusion,

mPEG-PCL nanoparticles containing drug can be a good option for controlled and gradual release of

Tamoxifen in cancer treatment. In general, results obtained from this stud present valuable information for

development of modern pharmaceutical systems and generation of polymers with high strength and greater

ratio of surface to volume in nanostructure, in particular mPEG-PCL-based nanoparticles.

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