Rahimi, Pegah

Simorgh Research Repository

    داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ و ﺧﺪﻣﺎت ﺑﻬﺪاﺷﺘﻲ درﻣﺎﻧﻲ ﻛﺮﻣﺎن  داﻧﺸﻜﺪه داروﺳﺎزي و ﻋﻠﻮم داروﻳﻲ    دﻛﺘﺮاي ﻋﻤﻮﻣﻲ داروﺳﺎزي ﭘﺎﻳﺎن ﻧﺎﻣﻪ        :ﻋﻨﻮانوزﻳﻜﻮﻟﻲ و ﻣﻴﺴﻠﻲ ﺗﻬﻴﻪ و ﺑﺮرﺳﻲ ﺧﺼﻮﺻﻴﺎت ﻓﻴﺰﻳﻜﻮﺷﻴﻤﻴﺎﻳﻲ ﺳﻮﺳﭙﺎﻧﺴﻴﻮن آﻟﺰاﻳﻤﺮي  واﺛﺮات آن ﺑﺮ ﺣﺎﻓﻈﻪ  و ﻳﺎدﮔﻴﺮي در ﻣﺪل 21C-N5-21Cدوﻗﻠﻮي  ﺳﻮرﻓﻜﺘﺎﻧﺖ  ﻣﻮش ﺻﺤﺮاﻳﻲ      :ﺗﻮﺳﻂ  ﭘﮕﺎه رﺣﻴﻤﻲ    :اﺳﺎﺗﻴﺪ راﻫﻨﻤﺎ  دﻛﺘﺮ ﻋﺒﺎس ﭘﺮداﺧﺘﻲ  دﻛﺘﺮ وﺣﻴﺪ ﺷﻴﺒﺎﻧﻲ        0801 :ﻪﺷﻤﺎره ﭘﺎﻳﺎن ﻧﺎﻣ                                                                   8931 ﺑﻬﺎر  Kerman University of Medical Sciences  Faculty of Pharmacy   Thesis . Pharm. D.    Title: Preparation of vesicular and micellar suspension of C12-5N-C12 Gemini surfactant and evaluation of their physicochemical characterization and their effects on memory and learning in Alzheimer’s rat model  By:  Pegah Rahimi    Supervisor: Dr. Abbas Pardakhty Dr. Vahid Sheibani      Spring 2019       Thesis NO: 1080                             ﭼﻜﻴﺪه:ﺷﻮد ﻛﻪ  در ﺑﺎﻋﺚ ﺗﺨﺮﻳﺐ ﺣﺎﻓﻈﻪ، رﻓﺘﺎر و ﺷﻨﺎﺧﺖ ﻣﻲ: ﺑﻴﻤﺎري آﻟﺰاﻳﻤﺮ ﻳﻚ ﺑﻴﻤﺎري ﻧﻮرودژﻧﺮاﺗﻴﻮ اﺳﺖ ﻛﻪ ﻣﻘﺪﻣﻪرود. در ﺣﺎل ﺣﺎﺿﺮ، ﻫﻴﭻ راه  ﻣﺆﺛﺮي ﺑﺮاي ﻧﻬﺎﻳﺖ در ﺳﻨﻴﻦ ﭘﻴﺮي ﺑﻪ ﺳﻤﺖ دﻣﺎﻧﺲ ﻳﺎ زوال ﻋﻘﻞ ﭘﻴﺶ ﻣﻲﭘﻴﺸﮕﻴﺮي و ﺑﻬﺒﻮد اﻳﻦ ﺑﻴﻤﺎري در اﻧﺴﺎن وﺟﻮد ﻧﺪارد و داروﻫﺎي  ﻣﻮﺟﻮد ﺗﻨﻬﺎ ﺑﻪ ﺗﺨﻔﻴﻒ ﻋﻼﺋﻢ ﺑﻴﻤﺎري ﻛﻤﻚ آﻣﻴﻨﻮ اﺳﻴﺪ و ﺗﺸﻜﻴﻞ  83-34ﺑﺎ   آﺳﻴﺐ ﺷﻨﺎﺳﻲ  آﻟﺰاﻳﻤﺮ، ﺗﺠﻤﻊ ﭘﭙﺘﻴﺪ آﻣﻴﻠﻮﺋﻴﺪ ﺑﺘﺎﻛﻨﻨﺪ. ﻓﺮآﻳﻨﺪ ﻛﻠﻴﺪي در  ﻣﻲﻫﺎي اﺧﻴﺮ ﺑﺮ روي دﺳﺘﻪ ﺟﺪﻳﺪي از ﻓﻴﺒﺮﻫﺎي آﻣﻴﻠﻮﺋﻴﺪي در ﻣﻐﺰ ﺑﻴﻤﺎران  اﺳﺖ.  ﺑﺮاﺳﺎس ﻣﻄﺎﻟﻌﺎﺗﻲ ﻛﻪ در ﺳﺎلﻮاص ﻣﻔﻴﺪي ﻫﺎ داراي ﺧﻫﺎ ﺑﻪ ﻧﺎم ژﻣﻴﻨﻲ ﺳﻮرﻓﺎﻛﺘﺎﻧﺖ اﻧﺠﺎم ﮔﺮﻓﺘﻪ اﺳﺖ، اﻳﻦ دﺳﺘﻪ از ﺳﻮرﻓﻜﺘﺎﻧﺖﺳﻮرﻓﻜﺘﺎﻧﺖﺑﺎﺷﻨﺪ. ( ﺑﺴﻴﺎر ﭘﺎﻳﻴﻦ، ﻛﺸﺶ ﺳﻄﺤﻲ ﻛﻢ و زﻳﺴﺖ ﺗﺨﺮﻳﺐ ﭘﺬﻳﺮ ﺑﻮدن ﻣﻲCMCﻣﺎﻧﻨﺪ:ﻏﻠﻈﺖ ﺑﺤﺮاﻧﻲ ﻣﻴﺴﻞ )ﺷﻮﻧﺪ. ﺑﻪ ﻫﻤﻴﻦ ﻫﺎ ﻣﺎﻧﻊ ﺗﺠﻤﻊ ﻓﻴﺒﺮﻫﺎي آﻣﻴﻠﻮﺋﻴﺪي در ﻣﺤﻴﻂ آزﻣﺎﻳﺸﮕﺎﻫﻲ  ﻣﻲﻫﻤﭽﻨﻴﻦ اﻳﻦ ﻧﻮع ﺳﻮرﻓﺎﻛﺘﺎﻧﺖﺑﺮ اﺧﺘﻼل   )21C-N5-21C(رﻓﺎﻛﺘﺎﻧﺖ ﻣﻨﻈﻮر در ﻣﻄﺎﻟﻌﻪ ﺣﺎﺿﺮ، اﺛﺮات ﺳﺎﺧﺘﺎرﻫﺎي ﻣﻴﺴﻠﻲ و ﻧﻴﻮزوﻣﻲ از ژﻣﻴﻨﻲ ﺳﻮ  ﺣﺎﻓﻈﻪ ﻧﺎﺷﻲ از ﺗﺠﻮﻳﺰ ﺑﺘﺎ آﻣﻴﻠﻮﺋﻴﺪ، ﺑﻪ ﺻﻮرت درون ﺗﻨﻲ ﻣﻮرد ﺑﺮﺳﻲ ﻗﺮار ﮔﺮﻓﺖ.ژﻣﻴﻨﻲ ﺳﻮرﻓﺎﻛﺘﺎﻧﺖ ﻣﻮرد اﺳﺘﻔﺎده ﻗﺮار ﮔﺮﻓﺖ. ﻛﻠﺴﺘﺮول و  ﺴﻞﻴﻣ ﻪﻴﺗﻬ يﺑﺮا CMCﻏﻠﻈﺖ  ﺑﺮاﺑﺮ 0001: روش ﻛﺎر ﻪﻳﻣﻮرد اﺳﺘﻔﺎده ﻗﺮار ﮔﺮﻓﺘﻨﺪ. ﺗﺠﺰ ﻠﻢﻴﻫﻴﺪراﺗﺎﺳﻴﻮن ﻓﻫﺎ ﺑﺎ اﺳﺘﻔﺎده از روش  ﻴﻮزومﻓﺮﻣﻮﻻﺳﻴﻮن ﻧ يﺑﺮاﻫﺎي ﻛﺎﺗﻴﻮﻧﻲ  ﻲﺣﺴ يﻫﺎ ﺴﺘﻢﻴﺳ يﺪارﻳو ﭘﺎ(  )reziS retsaM nrevlaM ﺰرﻴﻧﻮر ﻟ ﻲاﻧﺪازه ذره ﺗﻮﺳﻂ روش ﭘﺮاﻛﻨﺪﮔ ﻞﻴو ﺗﺤﻠﻫﺎي ﻣﻴﻜﺮوﺳﻜﻮﭘﻲ  و در ﻓﻮاﺻﻞ زﻣﺎﻧﻲ ﻣﺸﺨﺺ ﻧﻤﻮﻧﻪ ﮔﺮاد اﻧﺠﺎم ﺷﺪ ﻲﺳﺎﻧﺘدرﺟﻪ  4- 8دﻣﺎي  ﻣﺎه در 21 ﻲدر ﻃﺳﻮرﻓﻜﺘﺎﻧﺖ ژﻣﻴﻨﻲ  ﻮنﻴو ﻓﺮﻣﻮﻻﺳ 24-1βA ﻖﻳﺗﺰر يﺑﺮاﺟﺮاﺣﻲ اﺳﺘﺮﻳﻮﺗﺎﻛﺲ دﺳﺘﮕﺎه ﻣﻮرد ﺑﺮرﺳﻲ ﻗﺮار ﮔﺮﻓﺖ. ﺳﻮرﻓﻜﺘﺎﻧﺖ  ژﻣﻴﻨﻲ ﻣﺨﺘﻠﻒ يﻫﺎ ﻮنﻴﻣﻮرد اﺳﺘﻔﺎده ﻗﺮار ﮔﺮﻓﺖ. اﺛﺮات ﻓﺮﻣﻮﻻﺳ ﺗﺎﻳﻲ ﻣﻮش ﺻﺤﺮاﻳﻲ 7ﮔﺮوه  7در ﻗﺮار  ﻲﻣﻮرد ﺑﺮرﺳ ﺲﻳﺗﻮﺳﻂ ﻣﺎز آب ﻣﻮر ﻳﻲﺮادر ﻣﻮش ﺻﺤ βAاز  ﻲو اﺧﺘﻼل ﺣﺎﻓﻈﻪ ﻧﺎﺷ يﺮﻴﺎدﮔﻳدر ﺑﻬﺒﻮد    .ﺖﮔﺮﻓﻣﺎه  21ﺑﻮده و در ﻣﺪت  5 mµ: ﻓﺮﻣﻮﻻﺳﻴﻮن وزﻳﻜﻮل اﻧﺘﺨﺎﺑﻲ داراي  ﻣﻴﺎﻧﮕﻴﻦ ﻗﻄﺮ ﻛﻤﺘﺮ از ﻧﺘﺎﻳﺞ و ﺑﺤﺚﺑﺨﺶ ﻳﺎدﮔﻴﺮي  در βAي درﻳﺎﻓﺖ ﻛﻨﻨﺪهﮔﺮوه در ﭘﺎﻳﺪاري آن ﺗﻐﻴﻴﺮي ﻧﻜﺮد. ﻧﺘﺎﻳﺞ ﺑﺨﺶ رﻓﺘﺎري ﺑﻴﺎﻧﮕﺮ آن ﺑﻮد ﻛﻪ ﺟﻬﺖ ﻳﺎﻓﺘﻦ ﺳﻜﻮي ﭘﻨﻬﺎن  ﻃﻲ ﺷﺪهﻣﺴﺎﻓﺖ و زﻣﺎن درﻣﻮرد ، و ﻛﻨﺘﺮل ﻧﺴﺒﺖ ﺑﻪ ﮔﺮوه ﺷﺎﻫﺪداري اﺧﺘﻼف ﻣﻌﻨﻲﻃﻲ ﻣﺪت زﻣﺎن  ﺑﺎ ﺷﺎﻫﺪ درﻣﻮرد	βAﮔﺮوه ي داري در ﻣﻘﺎﻳﺴﻪاﺧﺘﻼف ﻣﻌﻨﻲ. در ﺑﺨﺶ  ﺣﺎﻓﻈﻪ ﻧﻴﺰ ﻣﺸﺎﻫﺪه ﻧﺸﺪﺖ و ﺳﺮﻋ ﺗﻌﺪاد دﻓﻌﺎت ورود ﺑﻪ ﻣﻨﻄﻘﻪ ﻫﺪفدر ﻣﻨﻄﻘﻪ ﻫﺪف و  ﻃﻲ ﺷﺪه و درﺻﺪ ﻣﺴﺎﻓﺖﺷﺪه ﺗﺎ ﻣﻨﻄﻘﻪ ﻫﺪف در ﻣﻘﺎﻳﺴﻪ ﺑﺎ  ﻛﺮده ﺑﻮدﻧﺪدرﻳﺎﻓﺖ ، ﻣﻴﺴﻞ  βAﻛﻪ ﻋﻼوه ﺑﺮ ﮔﺮوﻫﻲ در ﺑﺨﺶ ﻳﺎدﮔﻴﺮي  ﻣﺸﺎﻫﺪه ﻧﺸﺪ.ﺷﻨﺎي ﺣﻴﻮان ، اﻣﺎ ﺪادﻧﺪﻧﺟﻬﺖ ﭘﻴﺪا ﻛﺮدن ﺳﻜﻮ ﻧﺸﺎن  ﻃﻲ ﺷﺪهﻣﺴﺎﻓﺖ و زﻣﺎن در ﻣﻮرد ﻣﻌﻨﻲ داري ، اﺧﺘﻼف βAﮔﺮوه درﻣﻮرد ﻓﺎﺻﻠﻪ ﻃﻲ ﺷﺪه و ﺑﺎ ﮔﺮوه  ﻣﻴﺴﻞدر ﻣﻘﺎﻳﺴﻪ ﺑﺎ ﮔﺮوه  ﻧﻴﻮزوم درﻳﺎﻓﺖ ﻛﺮده ﺑﻮدﻧﺪ βAﻛﻪ ﻋﻼوه ﺑﺮ ﮔﺮوﻫﻲ ﻫﺮ و در ﺑﺨﺶ ﺣﺎﻓﻈﻪ،  ري را ﻧﺸﺎن دادﻣﻌﻨﻲ دا ﻛﺎﻫﺶدر ﻣﻮرد زﻣﺎن ﻃﻲ ﺷﺪه ﺗﺎ ﺳﻜﻮ  βA ﻫﺎي ﺷﺎﻫﺪ، ﻣﻴﺴﻞ و-ﻫﺎ ﻣﺸﺎﻫﺪه ﻧﺸﺪ. ﻧﺘﺎﻳﺞ ﮔﺮوهدر ﻣﻘﺎﻳﺴﻪ ﺑﺎ ﺳﺎﻳﺮ ﮔﺮوهداري در ﻣﻮرد ﻓﺎﻛﺘﻮرﻫﺎي ﻣﻮرد ﻧﻈﺮ ﺗﻐﻴﻴﺮات ﻣﻌﻨﻲدو ﮔﺮوه ﻳﺎﻓﺖ ﻛﺮده ﺑﻮدﻧﺪ ﻧﺸﺎن داد ﻛﻪ از ﻟﺤﺎظ ﺗﻤﺎﻣﻲ ﻓﺎﻛﺘﻮرﻫﺎ ﻫﻴﭻ ﺗﻔﺎوت ﻣﻌﻨﻲ داري ﻛﻪ ﺗﻨﻬﺎ ﻣﻴﺴﻞ ﻳﺎ ﻧﻴﻮزوم درﻫﺎﻳﻲ ﻫﺎي ﻣﻴﺴﻞ و ﻧﻴﻮزوم ﺑﻪ ﺗﻨﻬﺎﻳﻲ اﺛﺮي ﺑﺮ ﻳﺎدﮔﻴﺮي و ﻫﺎي ﺷﺎﻫﺪ و ﻛﻨﺘﺮل ﻧﺪاﺷﺘﻨﺪ. ﺑﻨﺎﺑﺮاﻳﻦ ﻓﺮﻣﻮﻻﺳﻴﻮنﺑﺎ ﮔﺮوه، ﺑﺮاي  21C-N5-21Cﻣﻴﺴﻞ و ﻧﻴﻮزوم ﻫﺎي ﻫﺮ دو ﻓﺮﻣﻮﻻﺳﻴﻮن ﺣﺎﻓﻈﻪ ﺣﻴﻮاﻧﺎت ﻧﺪاﺷﺘﻨﺪ. اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﻧﺸﺎن داد ﻛﻪ از ﻛﻴﻔﻴﺖ  در اﻳﻦ ﻣﻄﺎﻟﻌﻪ اﺣﺘﻤﺎﻻ ﺑﻪ دﻟﻴﻞ اﻳﻨﻜﻪ ﺑﺘﺎآﻣﻴﻠﻮﺋﻴﺪ اﺳﺘﻔﺎده ﺷﺪه اﻣﺎﻨﺪ، ﻣﻲ ﺑﺎﺷﻣﻮﺛﺮ آﻟﺰاﻳﻤﺮ  ﺑﻴﻤﺎريرﻓﻊ ﺳﻲ و ﻧﻴﺎز ﺑﻪ ﻣﻄﺎﻟﻌﺎت ﺑﻴﺸﺘﺮ در زﻣﻴﻨﻪ ﺑﺎﻓﺖ ﺷﻨﺎرا ﻧﺸﺎن ﻧﺪادﻧﺪ و ﻣﻄﻠﻮﺑﻲ ﺑﺮﺧﻮردار ﻧﺒﻮد، ﺗﻔﺎوت ﻣﻌﻨﻲ داري   وﺟﻮد دارد.  VIﺑﺎ ﻗﺎﺑﻠﻴﺖ ﺗﺰرﻳﻖ   ﻧﺎﻧﻮﻧﻴﻮزوم ﻫﻤﭽﻨﻴﻦ ﺳﻨﺘﺰ ﻓﺮﻣﻮﻻﺳﻴﻮنيﺪﻴﻠﻛ تﺎﻤﻠﻛ.ﻞﺴﻴﻣ ،لﻮﻜﻳزو ،ﻲﻨﺗ نورد ،ﺖﻧﺎﺘﻛﺎﻓرﻮﺳ ﻲﻨﻴﻣژ ،ﺮﻤﻳاﺰﻟآ :  Abstract  Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder that degrades memory, cognition and behavior and finally leads to dementia in the elderly. At present, no effective treatment can prevent and cure this disease in human beings, and available drugs can only slightly alleviate AD symptoms. The accumulation of a peptide of 38-43 amino acids (Aβ), in the form of fibrillar plaques, was one of the main reasons for AD. Gemini surfactants are new surfactant with useful properties such as low CMC, low surface tension and biodegradability. According to in vitro studies, Gemini surfactants can disassemble Aβ fibrils, so they may become new therapeutic strategies for AD. At this study, the micelle and noisome was prepared by using Gemini surfactant (C12-5N-C12) and evaluated the effects of them in preventing AD caused by Aβ injection in rat models. Method:  the 1000 fold * was used to CMC concentration for preparing micelles. Cholesterol and cationic Gemini surfactant were used for formulation of niosomes by film hydration method. Particle size analysis was carried out by laser light scattering technique (Malvern Master sizer) and stability of vesicular systems during 12 months stage at 4-8 ºC was also carried out. stereotaxic surgery device was used for hippocampus injection of Aβ 1-42 and Gemini surfactant formulations in 7 groups of 7 rats. The effects of different formulations of Gemini surfactant on improving learning and memory impairment induced by Aβ in rats were checked by Morris water maze. Results and discussion: The mean volume diameter of the selected vesicles was less than 5 µm and didn’t change during stability evaluation period of 12 months.The rats which received Aβ (amyloid beta group) didn’t have significant differences compared to sham and control groups for swimming distance (cm) and escape latency (sec) to find hidden platform in learning tests and also in memory tests they didn’t have significant differences compared to sham and control groups for escape latency (sec) and percentage of swimming distance in target zone and frequency and velocity to find hidden platform. Rats which received both Aβ and micelle didn’t have significant differences compared to Aβ group for swimming distance (cm) and escape latency (sec) to find hidden platform in learning tests, but  Rats which received both Aβ and noisome formulation significantly had shorter swimming distance than micelle group and shorter escape latency to find hidden platform than sham, Aβ and micelle groups in learning tests and in the prob trial, both groups didn’t have significant differences compared to other groups. The groups which received only micelle or noisome didn’t have significant differences compared to sham and control groups. This showed that formulations alone didn’t have any effect on learning and memory. This study showed that both noisome and micelle formulations(C12-5N-C12) were effective in the treatment of Alzheimer’s disease. But probably because of the low quality of the Aβ used in this study didn’t show significant differences. Hence more investigations should be done about histopathology studies and synthesis nano-niosome formulation of Gemini surfactant that make them capable for IV injection. Key words: Alzheimer, Gemini surfactant, in vivo, vesicle, micelle   

تهیه و بررسی خصوصیات فیزیکوشیمیایی سوسپانسیون وزيكولي و میسلی سورفکتانت دوقلوی C12-5N-C12 واثرات آن بر حافظه  و یادگیری در مدل آلزایمری موش صحرايي

http://eprints.kmu.ac.ir/31106/1/7135.pdf

تهیه و بررسی خصوصیات فیزیکوشیمیایی سوسپانسیون وزيكولي و میسلی سورفکتانت دوقلوی C12-5N-C12 واثرات آن بر حافظه و یادگیری در مدل آلزایمری موش صحرايي

Abstract

Similar works

Full text

Available Versions

Simorgh Research Repository