توسعه و ارزیابی خصوصیات لیپوزوم بهینه‌یابی شده جهت درون‌پوشانی کورکومین

نوع مقاله : مقاله پژوهشی

نویسندگان

• سیده فاطمه موسوی بایگی ¹
• آرش کوچکی ¹
• بهروز قرآنی ²
• محبت محبی ¹

¹ گروه علوم و صنایع غذایی، دانشکده کشاورزی، دانشگاه فردوسی مشهد، مشهد، ایران

² گروه نانوفناوری مواد غذایی، موسسه پژوهشی علوم و صنایع غذایی (RIFST)، کیلومتر 12 بزرگراه آسیایی مشهد-قوچان، صندوق پستی: 356-157-91895، مشهد، ایران

https://doi.org/10.22067/ifstrj.2021.73945.1118

چکیده

کورکومین به‌عنوان یک ترکیب زیست فعال چربی‌دوست دارای خواص سلامتی‌بخش ویژه‌ای می‌باشد اما پایداری کم و حساسیت بالای آن موجب محدودیت دسترسی زیستی این ماده شده است. هدف از این پژوهش طراحی و توسعه سیستم حامل لیپوزومی جهت ریزپوشانی کورکومین است. درون پوشانی ترکیبات حساس از جمله کورکومین در ساختار لیپوزومی، می تواند روشی موثر بر حفاظت آنها طی شرایط هضم دستگاه گوارشی باشد. هدف از این پژوهش، ارزیابی تاثیر میزان لستین (08/0- 02/0 گرم)، نسبت لستین: کلسترول (4- 5/0)، میزان کورکومین (6- 5/1 میلی‌گرم) و زمان تیمار فراصوت (5- 1 دقیقه) بر تولید لیپوزوم‌های حاوی کورکومین بود. نمونه بهینه با آزمون‌های تعیین اندازه ذرات، توزیع اندازه ذرات، پتانسیل زتا و بازده درون پوشانی به روش تکنیک سطح پاسخ تعیین گردید و سپس ماهیت فیزیکی، ساختار مولکولی و همچنین رفتار رهایش کورکومین درون پوشانی شده در سه شرایط شبیه سازی دهان، معده و روده برای نمونه بهینه مورد ارزیابی قرار گرفت. نتایج نشان داد که همه متغیرهای مستقل بر اندازه ذرات لیپوزوم دارای اثر معنی‌دار (01/0>p) بود و افزایش نسبت لستین: کلسترول موجب یکنواختی هرچه بیشتر اندازه ذرات گردید. لستین تنها جزء اثرگذار بر پتانسیل ذرات تعیین شد و افزایش زمان امواج فراصوت موجب افزایش بازده درون پوشانی کورکومین در لیپوزوم گردید. نقطه بهینه تهیه لیپوزوم با بالاترین بازده درون پوشانی (0/1± 02/69 درصد) وکمترین اندازه ذرات (09/0± 174/214 نانومتر)، توزیع اندازه ذرات (02/0± 105/0) و پتانسیل زتا (31/0± 541/16- میلی‌ولت) در شرایط میزان لستین 08/0 گرم، نسبت لستین: کلسترول 4:1، میزان کورکومین 16/4 میلی‎‌گرم و تیمار فراصوت 5 دقیقه توسط نرم‌افزار دیزاین اکسپرت معرفی شد. کورکومین در ذرات کروی لیپوزوم بهینه به حالت آمورف بود. پایداری این لیپوزوم‌ها طی زمان تحت تاثیر دما بوده به‌طوری که در مقایسه با دمای 4درجه سانتی‌گراد، کورکومین بیشتری از لیپوزوم در دمای 25 درجه سانتی‌گراد رهایش یافته بود. همچنین رفتار رهایش کورکومین در شرایط دستگاه گوارش اساس مکانسیم انتشار بود.

کلیدواژه‌ها

• بهینه‌یابی
• رفتار رهایش
• کورکومین
• لیپوزوم

موضوعات

• مهندسی مواد غذایی

عنوان مقاله [English]

Evaluation of Behavior and Modeling of Curcumin Release from Liposomes under Simulated Gastrointestinal Laboratory Conditions

نویسندگان [English]

• Fateme Mousavi Baygi ¹
• Arash Koocheki ¹
• Behrooz Ghorani ²
• Mohebbat Mohebbi ¹

¹ Department of Food Science and Technology, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran

² Department of Food Nanotechnology, Research Institute of Food Science and Technology (RIFST), km 12 Mashhad-Guchan Highway, PO box: 91895-157-356, Mashhad, Iran

چکیده [English]

Introduction
 Curcumin, as a natural polyphenolic nutraceutical has been shown many health-promoting effects, mainly associated with its chemical structure. In various studies, different properties of this compound, including anti-tumor and anti-cancer activity, reduction of blood and liver cholesterol levels, increase of immune function, prevention of cardiovascular diseases, prevention of damage to biological membranes against peroxidation and anti-inflammatory properties have been reported. Despite possessing a potential health benefits to humans, the susceptibility of this polyphenol towards environmental conditions and low chemical stability has restricted the direct usage of curcumin into aqueous-based food formulations. The encapsulation of curcumin in liposomes is a potentially effective way to protect them from degradation during passing the digestive system.
Materials and Methods
Curcumin (powder, purity greater than 99%, 368.38 g/mol), lecithin, cholesterol (C3045-25G), pancreacin (extracted from porcine pancreas, P7545-25G), bile salts (B8756-10G) and calcium chloride (CaCl₂) was obtained from Sigma Aldrich (USA). Consumable ethanol was purchased from Pars Ethanol Company (96%, Iran). Lipase enzyme (extracted from pig pancreas, L8070) and pepsin (activity 3500-3000 NFU/g, P8390) were obtained from Solarabio (China). Potassium chloride, dipotassium hydrogen phosphate (K2HPO4) and alpha-amylase enzyme with a purity of at least 99% were obtained from Merck, Germany, sodium chloride (NaCl), sodium bicarbonate (NaHCO3) and calcium chloride were obtained from Sigma. The effect of lecithin content (0.02- 0.08 g), lecithin cholesterol ratio (0.5- 4), curcumin level (1.5- 6mg) and ultrasound treatment time (1-5 minutes) on production of liposomes containing curcumin was evaluated. The particle size, particle size distribution, zeta potential and efficiency were determined by response surface methodology. Furthermore, physical nature, molecular structure, physical stability at 4ºC and 25ºC and release behavior of curcumin loaded-liposome in mouth, stomach and intestines were explored.
Results and Discussion
 The results showed that all independent variables had a significant effect on liposome particle size and increasing the ratio of lecithin: cholesterol caused more uniform particle size. Lecithin was determined to be the only component affecting the zeta potential of liposome particles, and increasing the ultrasound time increased the efficiency of curcumin encapsulation in liposomes. The optimal point of liposome preparation conditions in the amount of 0.08 g lecithin, 4: 1 the ratio of lecithin: cholesterol, 4.16 mg curcumin and 5 minutes the ultrasound treatment was introduced by Design Expert software. In addition, curcumin was amorphous in optimal liposome spherical particles. Furthermore, the results of TEM showed that the liposomes are in the form of single-layer particles, spherical and without membrane rupture. This makes the bilayered nature of the vesicles clearly visible in this micrograph. The size of the particles obtained from this method was consistent with the data obtained from the dynamic light scattering method. From the results of infrared spectroscopy, it can be seen that curcumin is trapped in the liposome through hydrogen bonding in the double-layered vesicle of the liposome, the phenolic ring of curcumin with the phospholipid head group, as well as the hydrophobic interactions of the aromatic rings with the acyl phospholipid chains. Liposomes were more stable at refrigeration temperature. A very small amount of curcumin was released in the simulated oral phase, which is probably due to the short time and lack of specific enzymes to disrupt the phospholipid bilayers of the liposome. Although the pepsin enzyme is unable to penetrate the liposome membrane, acidic conditions change the angle of the head and tail groups of the lipids and lead to a change in the surface charge of the liposomes. The release of curcumin from liposome vesicles was greatly increased in the intestine. This sudden increase is due to the presence of bile salts as an emulsifying agent that can disrupt the phospholipid membrane and make the membrane more fluid. In addition, pancreatic lipase is adsorbed on the surface of lipids and then hydrolyzes the phospholipid into 2-acyl and 1-acyl lysophospholipids and free fatty acids. The release behavior of curcumin under gastrointestinal conditions was based on the Fick mechanism.

کلیدواژه‌ها [English]

• Curcumin
• Liposome
• Optimization
• Release behavior

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