بررسی فرایند تولید نانوذرات لیپیدی جامد؛ تأثیر پارامترهای فرآیند بر ویژگی های پیش امولسیون و امولسیون نهایی

نویسندگان
گروه نانوفناوری موادغذایی، موسسه پژوهشی علوم و صنایع غذایی، مشهد، ایران
چکیده
نانوذرات لیپیدی جامد یکی از سیستم های انتقال کاربردی است که در سال های اخیر جهت دورن پوشانی مواد فعال زیستی بسیار مورد توجه قرار گرفته است. یکی از خصوصیات فیزیکوشیمیایی مهم این نانوحامل ها اندازه ذرات است که بسیار تحت تاثیر فرمولاسیون و فرایند تولید آنها قرار می گیرد. شرایط نامناسب فرایند تولید نانوحامل ها در مرحله پیش امولسیون و امولسیون اصلی باعث ایجاد اندازه ذرات نامناسب و همچنین ناپایداری امولسیون و تشکیل ژل می گردد. بنابراین در این پژوهش فرایند تولید نانوذرات لیپیدی جامد تولید شده با دو لیپید کمپریتول و پریسیرول به صورت جداگانه با روش هموژنیزاسیون گرم بررسی و بهینه سازی شد. بدین جهت پارامترهای فرایند مانند زمان همزنی با استفاده از همزن دور بالا جهت تهیه پیش امولسیون و همچنین شدت میدان نوسان و زمان اعمال فراصوت بر پیش امولسیون جهت دستیابی به کوچک ترین اندازه ذرات نانوحامل ها مورد بررسی قرار گرفت. در تهیه پیش امولسیون، کوچک ترین اندازه ذره در زمان ۱۸۰ ثانیه ودور همزن ۱۶۰۰۰ دور در دقیقه در نانوذرات پرسیرول (nm) ۳± ۳۷۳ و در نانوذرات کمپریتول (nm) ۴± ۶۱۹ بود. همچنین در تهیه امولسیون نهایی میدان نوسان ۴۰٪ و زمان ۳ دقیقه کوچک ترین اندازه نانوذرات لیپیدی جامد پریسیول ((nm) ۲± ۲۵۹) و نانوذرات لیپیدی جامد کمپریتول ((nm) ۵± ۳۹۷) را ایجاد کرد. سپس خصوصیاتی مانند پراکندگی اندازه ذرات، پتانسیل زتا و مشاهدات بصری نانوحامل های تولید شده در شرایط بهینه تولید، بررسی شد. نتایج نشان داد که نانوذرات لیپیدی جامد پریسیرول علاوه بر اندازه ذرات کوچک تر دارای پتانسیل زتای بالاتری ( mV60/0 ± 30/12-) در مقایسه با نانوحامل کمپریتول ( mV17/0± 97/8-) بود. اما پراکندگی اندازه ذرات هر دو نانوحامل تفاوت معنی داری نداشت. همچنین مشاهدات بصری هر دو نانوحامل در پایان زمان نگهداری هیچ گونه ناپایداری را نشان نداد.
کلیدواژه‌ها

موضوعات


عنوان مقاله English

Evaluating the production process of Solid lipid nanoparticles: The effect of process parameters on the physicochemical properties of pre and final emulsion

نویسندگان English

Maryam Mohammadizadeh
Aram Bostan
Rassoul Kadkhodaee
Department of Food Nanotechnology, Research Institute of Food Science and Technology, PO Box: 91735-147, Mashhad, Iran
چکیده English

Solid lipid nanoparticles (SLN) are one of the appropriate delivery systems which attract enormous interest for encapsulating bioactive componds in recent years. One of the important physicochemical properties of SLNs is particle size that is influenced by formulation and production process parameters. Inappropriate conditions of the nanaocarrier production process in the pre and main emulsion steps cause unsuitable paricle size as well as unstable emulsion and gel formation. Therefore, in this research production process of SLN was investigated and optimized by hot homogenization method and with two lipids of Compritol and Precirol separately. Hence, homogenization time in preparation of pre emulsion and amplitude and time of ultrasonication in final emulsion production was studied to obtained the smallest particle size. In pre emulsion step, the smallest particle size for Compritol SLN (619±4 nm) and Precirol SLN (373±3 nm) obtained in 180 second mixing by ultra-turax in 16000 (rpm). In final emulsion, 40% amplitude and 3 minutes caused to attained smallest particle size in Compritol SLN (397±5 nm) and Precirol SLN (259±2 nm). Then polydispersity index (PDI), zeta potential and visual observation of nanocarriers with optimized particle size were examined. The results showed that Precirol SLN had higher zata potential (-12.3±0.6 mV) than Compritol SLN (-8.97±0.17mV) but PDI of two nanocarriers was not significantly different. Visual observation of both nanocarriers at the storage time showed no instability.

کلیدواژه‌ها English

Solid lipid nanoparticles
Ultrasound
Compritol
Precirol
particle size
1 Poornima, K. and Sinthya, R. 2017. Application of Various Encapsulation Techniques in Food Industries. International Journal of Latest Engineering Research and Applications. 2(10): 37-41.
2 Fathi, M., Mozafari, M.R. and Mohebbi, M. 2012. Nanoencapsulation of food ingredients using lipid based delivery systems. Trends in Food Science & Technology. 23:13-27.
3 Tamjidi, F., Shahedi, M., Varshosaz, J. & Nasirpour, A. 2013. Nanostructured lipid carriers (NLC): A potential delivery system for bioactive food molecules. Innovative Food Science and Emerging Technologies. 19: 29–43.
[4] Mehnert, W. & Mäder, K. 2012. Solid lipid nanoparticles Production, characterization and applications. Advanced Drug Delivery Reviews. 47(2-3): 165–196.
[5] Matos de Carvalho, S., Montanheiro Noronha, C., Floriani, C. L., Calegari Lino, R., Rocha, G., Casagrande Bellettini, I., José Ogliar, P. & Manique Barreto, P. L. 2013. Optimization of α-tocopherol loaded solid lipid nanoparticles by central composite design. Industrial Crops and Products. 49: 278– 285.
[6] Azhar, L. Bahari, S. and Hamishehkar, H. 2016 The Impact of Variables on Particle Size of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers; A Comparative Literature Review, Advanced Pharmaceutical Bulletin. 6(2): 153-151.
[7] Muller, R. H., Radtke, M. & Wissing, S. A. 2002. Nanostructured lipid matrices for improved microencapsulation of drugs. International Journal of Pharmaceutics. 242(1-2), 121-128.
[8] Garud, A., Singh, D and Garud, N. 2012. Solid Lipid Nanoparticles (SLN): Method, Characterization and Applications. International Current Pharmaceutical Journal. 1: 384-393.
[9] Yadav, N., Khatak, S. and Vir singh sara, V. 2013. Solid lipid nanoparticles- A review. International Journal of Applied Pharmaceutics. 5: 0975-7058.
[10] Chaturvedi, S. P. and Kumar, V. 2012. Production Techniques of Lipid nanoparticles: A Review. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 3: 525-541.
[11] Kamble, M. S., Vaidya, K. K., Bhosale, A. V. and Chaudhari, P. D. 2012. Solid lipid nanoparticles and nanostructured lipid carriers – an overview. International journal of pharmaceutical, chemical and biological sciences. 2: 681-691.
[12] Naseri, N., Valizadeh, H. and Zakeri-Milani, P. 2015. Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Structure, Preparation and Application. Advanced Pharmaceutical Bulletin. 5(3): 305-313.
[13] Zhang, M., Falkeborgm M., Zheng, Y., Yang, T. & Xu, X. 2013. Formulation and characterization of nanostructured lipid carriers containing a mixed lipids core. Colloids and Surfaces A: Physicochemical Engineering Aspects. 430: 76– 84.
[14] Aburahma, M. H. & Badr-Eldin, S. M. 2014. Compritol 888 ATO: a multifunctional lipid excipient in drug delivery systems and nanopharmaceuticals, Journal of Expert Opinion on Drug Delivery. 11(12): 1865-1883.
[15] Gattefosse paper sheet. Lipid excipients for oral, dermal, rectal and vaginal drug delivery. 2016. www.gattefosse.com
[16] Rosli, N.A., Hasham, R. and Abdul Aziz, A. 2018. Design and physicochemical evaluation of nanostructured lipid carrier encapsulated zingiber zerumbet oil by d- optimal mixture design. Journal of Technology. 80(3): 105-113.
[17] Gonzalez-Mira, E., Egea, M.A., Garcia, M.L. and Souto, E.B. 2010. Design and ocular tolerance of flurbiprofen loaded ultrasound-engineered NLC. Colloids and Surfaces B: Biointerfaces. 81:412–421.
[18] Rincón, M., Calpena, A.C., Fabrega, M., Garduño-Ramírez, M.L., Espinam M., Rodríguez-Lagunas, M.J. García, M.L. and Abrego, G. 2018. Development of Pranoprofen Loaded Nanostructured Lipid Carriers to Improve Its Release and Therapeutic Efficacy in Skin Inflammatory Disorders. Journal of nanomaterials, 8: 1322.
[19] Montanheiro Noronha, C., Ferreira Granada, A., Matos de Carvalho, S., Calegari Lino, R., Vinicius de O.B. Maciel, M. and Manique Barreto, P. L. 2013. Optimization of _-tocopherol loaded nanocapsules by the nanoprecipitation method. Industrial Crops and Products. 50 : 896– 903 .
[20] Obeidat, W. M., Schwabe, K., Müller, R. H. and Keck, C. M. 2010. Preservation of nanostructured lipid carriers (NLC). European Journal of Pharmaceutics and Biopharmaceutics. 76 : 56–67.
[21] Qian, C., Decker, E. A., Xiao, H. and McClemen, D. J. 2012. Solid Lipid Nanoparticles: Effect of Carrier Oil and Emulsifier Type on Phase Behavior and Physical Stability, Journal of the American Oil Chemists Society. 89(1): 17-28.
[22] Fathi, M. and Varshosaz, J. 2013. Novel hesperetin loaded nanocarriers for food fortification: Production and characterization. Journal of functional foods. 5:1382-1391.
[23] Pooja, D., Tunki, L., Kulhari, H., Reddy, B. B., Sistla, R. 2016. Optimization of solid lipid nanoparticles prepared by a single emulsification-solvent evaporation method. Data in Brief, 6: 15-19.
[24] Mendes, A.I., Silva, A.C., Catita, J.A.M., Cerqueira, F., Gabriel, C. and Lopes, C.M. 2013. Miconazole-loaded nanostructured lipid carriers (NLC) for local delivery to the oral mucosa: Improving antifungal activity. Colloids and Surfaces B: Biointerfaces. 111 : 755– 763.
[25] Liu, C. and Wu, C. 2010. Optimization of nanostructured lipid carriers for lutein delivery. Colloids and Surfaces A: Physicochem. Eng. Aspects. 353:149–156.
[26] Mirmajidi Hashtjin, A. and Abbasi, S. 2015. Optimization of ultrasonic emulsification conditions for the production of orange peel essential oil nanoemulsions. Journal of Food Science and Technology. 52(5):2679–2689.
[27] Franco, F., Pérez-Maqueda, L. A. and Pérez-Rodríguez, J. L. 2004. The effect of ultrasound on the particle size and structural disorder of a well-ordered kaolinite. Journal of Colloid and Interface Science. 274:107-117.
[28] Farid Aghaee, S., Ghanbarzadeh, B. and Hamishekar, H. 2015. Conjugated linoleic acid loaded nanostructured lipid carriers (NLC): optimization of particle size by response surface methodology. Journal of food research. 25(3):442-456.
[29] Das, S., Kiong Ng, W. & Tan, R. B. H. 2012. Are nanostructured lipid carriers (NLCs) better than solid lipid nanoparticles (SLNs): Development, characterizations and comparative evaluations of clotrimazole-loaded SLNs and NLCs. European Journal of Pharmaceutical Science, 47(1): 139–151.
[30] Tiwari, R. and Pathak, K. 2011. Nanostructured lipid carrier versus solid lipid nanoparticles of simvastatin: Comparative analysis of characteristics, pharmacokinetics and tissue uptake. International Journal of Pharmaceutics. 415: 232–243.
[31] Fang, J., Fang, C., Liu, C. and Su, Y. 2008. Lipid nanoparticles as vehicles for topical psoralen delivery: Solid lipid nanoparticles (SLN) versus nanostructured lipid carriers (NLC). European Journal of Pharmaceutics and Biopharmaceutics. 70: 633–640.
[32] Fan, F., Liu, G., Huang, Y., Li, Y. and Xia, Q. 2014. Development of a nanostructured lipid carrier formulation forincreasing photo-stability and water solubility of Phenylethyl Resorcinol. Applied Surface Science. 288:193–200.