Razi Journal of Medical Sciences
مجله علوم پزشکی رازی
RJMS
Medical Sciences
http://rjms.iums.ac.ir
39
journal39
2228-7043
2228-7051
en
jalali
1398
2
1
gregorian
2019
5
1
26
3
online
1
fulltext
fa
بررسی خصوصیات فیزیکوشیمیایی و الگوی رهایش DNA از کوپلیمرهای PLA-PEG-PLA حاوی درصد متفاوت PLA و PEG
Effect of different mass ratio of PLA: PEG segments in PLA-PEG-PLA copolymers on the physicochemical characterization and DNA release profile
بیوشیمی
Biochemistry
پژوهشي
Research
<strong><span style="color:#0070C0;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;">زمینه و هدف: </span></span></span></strong><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;">سیستم­های انتقال دارو با خاصیت کنترل </span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;">رهایش</span></span></span> <span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">DNA</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;">، امکان غلبه بر موانع خارج سلولی که سبب محدود شدن ژندرمانی میشود را فراهم آورده است. هدف از انجام این تحقیق بررسی تأثیر درصدهای متفاوت </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">PLA:PEG</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> در کوپلیمر </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">PLA-PEG-PLA</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> بر خصوصیات نانو ذرات حاصل بود.</span></span></span><br>
<strong><span style="color:#0070C0;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;">روش کار:</span></span></span></strong><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> در این تحقیق با تغییر نسبت­های </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">PLA:PEG</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> در کوپلیمر </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">PLA-PEG-PLA</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> نانو ذراتی با خاصیت کنترل اندازه، سرعت </span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;">رهایش</span></span></span> <span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">DNA</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> و بازده انتقال </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">siRNA-FAM</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> با موفقیت سنتز شد. بدین منظور کوپلیمرهای مختلفی از </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">PLA-PEG-PLA</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> در حضور لاکتیک اسید، پلیاتیلن گلیکول بهعنوان ماده اولیه و همچنین </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">stannous octoate</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> بهعنوان کاتالیز سنتز شد. سپس </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">DNA</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> یا </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">siRNA-FAM</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> با استفاده از تکنیک </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">double emulsion solvent evaporation technique</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> توسط کوپلیمر </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">PLA-PEG-PLA</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> انکپسوله شد. خصوصیات نانو ذرات حاصل از قبیل اندازه، مرفولوژی، الگوی </span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;">رهایش</span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;">، سمیت و بازده انتقال </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">siRNA-FAM</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> موردبررسی قرار گرفت.</span></span></span><br>
<strong><span style="color:#0070C0;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;">یافتهها:</span></span></span></strong> <span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;">تصاویر میکروسکوپ الکترونی نگاره نشان داد نانو ذرات حاصل دارای ساختار کروی و سطح صاف هستند. همچنین نتایج حاصل از </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">DLS</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> نشان داد با افزایش نسبت </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">PLA</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> در کوپلیمر </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">PLA-PEG-PLA</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> اندازه ذرات افزایش می­یابد علاوه براین نتایج ما نشان داد افزایش نسبت </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">PLA</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> در کوپلیمر </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">PLA-PEG-PLA</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> سبب کاهش سرعت </span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;">رهایش</span></span></span> <span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">DNA</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> از نانو ذرات </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">PLA-PEG-PLA/DNA</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> می­گردد. همچنین در این تحقیق تأثیر تغییر نسبت </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">PLA:PEG</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> بر بازده انتقال </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">siRNA-FAM</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> توسط میکروسکوپ فلورسانس و دستگاه فلوسایتومتری موردبررسی قرار گرفت</span></span></span><br>
<strong><span style="color:#0070C0;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;">نتیجهگیری:</span></span></span></strong><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> بین افزایش نسبت </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">PLA</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> در کوپلیمر </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">PLA-PEG-PLA</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> و افزایش بازده انتقال </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">siRNA-FAM</span></span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;"> رابطه مستقیم وجود دارد</span></span></span><span style="color:black;"><span style="font-family:b mitra;"><span style="font-size:10.0pt;">.</span></span></span><br>
<strong>Background:</strong> Adapting controlled release technologies to the delivery of DNA has the great potential to overcome extracellular barriers that limit gene delivery. This study investigates the effect of different mass ratio of PLA: PEG in the various tri block poly (lactic acid)-poly (ethylene glycol) - Poly (lactic acid) copolymer (PLA-PEG-PLA) on the properties of the resulting nanoparticles.<br>
<strong>Methods:</strong> The various tri block PLA-PEG-PLA copolymers were prepared via ring-opening polymerization by poly (ethylene glycol) (PEG), lactic acid and stannous octoate as raw material and catalyst, respectively. DNA or siRNA-FAM was incorporated into the tree block PLA-PEG-PLA copolymer using double emulsion solvent evaporation technique. Properties of these nanoparticles, such as morphology and particles size of nanoparticles, DNA release kinetics, in vitro cytotoxicity and siRNA-FAM transfer efficiency were evaluated.<br>
<strong>Results:</strong> Scanning electron microscope (SEM) showed that PLA-PEG-PLA/DNA nanoparticles have spherical morphology with smooth surface. Dynamic light scattering results showed the particle size of PLA–PEG-PLA copolymers increased with an increase in the mass ratio of PLA in PLA-PEG-PLA copolymers. The release profile of the PLA-PEG-PLA/DNA nanoparticles measured using nanodrop and the results showed that, decrease in mass ratio of PLA, increased the release profile of DNA from PLA-PEG-PLA/DNA nanoparticles. Moreover the percentage of siRNA-FAM transfer to MCF-7 cells by various PLA-PEG-PLA copolymers, measuring using flow cytometry and fluorescence microscopy.<br>
<strong>Conclusion:</strong> These results showed that there is same relation between the mass ratio of PLA and percentage of siRNA-FAM delivery into the MCF-7 cells
کوپلیمر PLA-PEG-PLA, الگوی رهایش DNA, siRNA-FAM, سلولهای MCF-7
PLA-PEG-PLA copolymer, Drug release profile, siRNA-FAM, MCF-7 cell.
1
12
http://rjms.iums.ac.ir/browse.php?a_code=A-10-3282-2&slc_lang=fa&sid=1
Fatemeh
Nahidi
فاطمه
ناهیدی
nahid2002ndb@yahoo.com
3900319475328460045118
000000021219487X
No
MSc biochemistry, Department of Biology, Ardabil Branch, Islamic Azad University, Ardabil, Iran
گروه زیست شناسی، واحد اردبیل، دانشگاه آزاد اسلامی، اردبیل، ایران
Hashem
Yaghoubi
هاشم
یعقوبی
yaghoubi_h@iauardabil.ac.ir
3900319475328460045119
3900319475328460045119
Yes
Department of Biology, Ardabil Branch, Islamic Azad University, Ardabil, Iran
گروه زیست شناسی، واحد اردبیل، دانشگاه آزاد اسلامی، اردبیل، ایران