In-Situ Forming Poloxamer-Based Hydrogel Containing Thiolated Chitosan Nanoparticles as Intranasal Galantamine Delivery System

In-Situ Forming Poloxamer-Based Hydrogel Containing Thiolated Chitosan Nanoparticles as Intranasal Galantamine Delivery System


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نویسندگان: ملیکا لطفی , آیلار نخلبند , خسرو ادیب کیا , مرضیه فتحی

عنوان کنگره / همایش: 5th international congress on pharmacy-updates , Iran (Islamic Republic) , تهران , 2022

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نویسنده ثبت کننده مقاله مرضیه فتحی
مرحله جاری مقاله تایید نهایی
دانشکده/مرکز مربوطه مرکز تحقیقات ریز فناوری دارویی
کد مقاله 78849
عنوان فارسی مقاله In-Situ Forming Poloxamer-Based Hydrogel Containing Thiolated Chitosan Nanoparticles as Intranasal Galantamine Delivery System
عنوان لاتین مقاله In-Situ Forming Poloxamer-Based Hydrogel Containing Thiolated Chitosan Nanoparticles as Intranasal Galantamine Delivery System
نوع ارائه سخنرانی
عنوان کنگره / همایش 5th international congress on pharmacy-updates
نوع کنگره / همایش بین المللی
کشور محل برگزاری کنگره/ همایش Iran (Islamic Republic)
شهر محل برگزاری کنگره/ همایش تهران
سال انتشار/ ارائه شمسی 1400
سال انتشار/ارائه میلادی 2022
تاریخ شمسی شروع و خاتمه کنگره/همایش 1399/11/26 الی 1400/11/29
آدرس لینک مقاله/ همایش در شبکه اینترنت https://journals.sbmu.ac.ir/acta/article/view/38044
آدرس علمی (Affiliation) نویسنده متقاضی Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran

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نویسنده نفر چندم مقاله
ملیکا لطفیاول
آیلار نخلبنددوم
خسرو ادیب کیاسوم
مرضیه فتحیچهارم

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عنوان متن
کلمات کلیدیNasal drug delivery, Alzheimers disease, Poloxamer, Nanoparticles, Galantamine, Thiolated chitosan
خلاصه مقالهAlzheimers disease (AD) is a progressive and irreversible neurodegenerative disease. Many neurodegenerative diseases require the efficient delivery of drugs to the brain. Considering the blood-brain barrier, drug delivery approaches for AD is limited. To overcome this problem, delivering the drug via the nasal route seems to be an appropriate approach as an alternative way to the systemic administration due to direct targeting of the brain. In this study, in order to optimize the drug delivery of AD, a new drug delivery system as a mucoadhesive in-situ forming hydrogel for Galantamine was prepared To this end, Mucoadhesive nanoparticles (NPs) were prepared by thiolation of chitosan (TCS) with mercaptopropionic acid. The number of thiol groups was measured using Ellmans reagent (DTNB dye). The Galantamine-loaded TCS NPs were synthesized by the two ionic gelation methods (via sodium tripolyphosphate) and desolvation technique (via Glutaraldehyde). After ultracentrifugation, the entrapment efficiency of Galantamine was estimated by a UV spectrophotometer at λmax of 289 nm. Three different concentrations of Poloxamer solution were prepared by the cold method. The concentration with the suitable gelation time and gelation temperature was then attained. The amount of the Galantamine-loaded NPs required as the therapeutic dose was calculated based on the entrapment efficiency. Two different amounts of NPs containing the drug were dispersed in 4 mL of poloxamer 18% gel and the achieved hydrogel at 37 ℃ was then sonicated. In-vitro release studies were carried out in pH 6.4 phosphate-buffered saline media using the dialysis bag. Fourier transform infrared (FT-IR) spectroscopy was used to analyze the structure of prepared formulations. In-vitro cell cytotoxicity of prepared hydrogel on CaCO2 cells (nasal mucosal cell model) was evaluated using the MTT method. The cell viability of hydrogels was determined by DAPIstaining and live/dead kit, too. The obtained results demonstrated that the thiolation value of CS was 198.6 ± 18.7 µmol S. g-1 CS, which is a convenient result based on reported works. In the preparation of TCS NPs via the ionic gelation method, by increasing the amount of TPP, the particle size increased and the zeta potential decreased. The mean size and zeta potential of NPs prepared by the desolvation method were 238.7 nm and 22.9 mV, respectively. The drug entrapment efficiency of Galantamine in the prepared NPs by ionic gelation method was zero, while the prepared NPs by desolvation method indicated encapsulation efficiency equal to 30%. As the concentration of Poloxamer 407 solution increased, gelling temperature and the time required for gelling decreased. Thus, according to the temperature of the intranasal environment (32-35 °C), Poloxamer 18% has the best concentration to prepare in-situ forming hydrogel for drug delivery via the intranasal route. Drug release from the hydrogel containing drug loaded-TCS NPs was slower and more controlled compared to the hydrogel containing the drug without NPs, which will lead to more effective drug delivery. Our results confirmed that Poloxamer hydrogels containing drug-loaded-TCS NPs are non-toxic for encapsulation of Galantamine and indicated high cell viability.

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