طراحی و بهینه سازی فرمولاسیون پوستی ژل نیوزومال حاوی پاروکستین و ارزیابی درون تن جهت دارورسانی در درمان اختلال اضطرابی عمومی و اختلال ترس

نویسندگان
شیوا مسائلی
عرفانه قسامی
محمد ربانی
ناصر توکلی
دانشگاه علوم پزشکی اصفهان
چکیده
مقدمه: پاروکستین یکی از موثرترین مهارکننده‌های بازجذب سروتونین است که به دلیل متابولیسم عبور اول کبدی و تشدید اثرات نامطلوب ناشی از نوسانات غلظت با اشکالات قابل‌توجهی روبروست. دارورسانی ترانس درمال یکی از استراتژی‌های حذف عبور اول کبدی است که در آن استفاده از نیوزوم‌ها به دلیل افزایش قابل‌توجه نفوذ دارو موردتوجه قرارگرفته‌است.

روش: ژل نیوزومال بارگیری‌شده با پاروکستین براساس متغیرهای مختلف با استفاده از نرم‌افزار دیزاین اکسپرت (ورژن 7) طراحی و بهینه‌سازی‌شد. سپس مطالعات تکمیلی برون‌تن روی نیوزوم‌های بهینه انجام و دیسپرسیون این نیوزوم ها وارد پایه هیدروژل HPMC شد. در مرحله بعد، هیدروژل حاوی نیوزوم‌ها در مدل‌های حیوانی اختلالات اضطراب عمومی و هراس، به ترتیب با استفاده از maze elevated plus وmaze elevated-T بررسی‌شد.

یافته‎ها: فرمول بهینه دارای اندازه ذرات 28/05±417/0 نانومتر، توزیع اندازه ذره‌ای 0/06±0/31، پتانسیل زتا 0/42±12/80 میلی ولت، کارایی بارگیری 0/47±72/85 درصد و کارایی رهش 0/55 ± 71/94 درصد طی 4 ساعت بود. نتایج مطالعات حیوانی نشان‌داد که اثربخشی درمان با فرمولاسیون پیشنهادی به‌طور معنی‌داری (P<0.05) در مدل‌های حیوانی در مقایسه با گروه‌های دریافت‌کننده داروی آزاد و نرمال‌سالین بهبودیافت.

نتیجه‎گیری: عملکرد مناسب برون‌تن و درون‌تن هیدروژل حاوی نیوزوم‌های لودشده با پاروکستین این پتانسیل را نشان‌داد که به‌عنوان یک سیستم دارورسانی جایگزین برای فرم خوراکی جهت درمان اختلال اضطراب عمومی و هراس موردبررسی بیشتر قرارگیرد.
کلیدواژه‌ها
پاروکستین
دارورسانی از طریق پوست
نیوزوم
اختلال اضطراب عمومی
اختلال هراس

عنوان مقاله English

Design and optimization of transdermal niosomal gel loaded with paroxetine for general anxiety and panic disorders

نویسندگان English

shiva masaeli
erfaneh ghassami
mohammed rabbani
isfahan university of medical sciences
چکیده English

Introduction: Paroxetine is an effective serotonin reuptake inhibitor, but its bioavailability is challenged by the to hepatic first pass effect, resulting in blood level fluctuations that negatively affect its therapeutic effects. Transdermal drug delivery could be used as a solution to this issue, and noisome are suggested as a solution to penetration enhancement of drugs at this point in administration.

Methods: In the current study, paroxetine-loaded niosomes were optimized for pharmaceutical characteristics Design Expert Software (ver.7) regarding the pharmaceutical characteristics. Then, the dispersion in HPMC hydrogel medium was dispersed, and the in vivo efficacy of this drug delivery system was investigated in animal models using elevated plus maze and elevated t-maze methods.

Results: The optimum formulation had a particle size of 417.40±28.05 nm, the particle size distribution of 0.31±, zeta potential of 12.8±0.42 mV, entrance efficiency of 72.85±0.47%, and release efficiency of 71.94±0.55%. Treatment of Bulb/c mice with this formulation via transdermal route of administration resulted in higher efficacy (p<0.05) compared with the positive and negative control groups.

Conclusion: The proposed formulation showed rather acceptable in vitro and in vivo efficacy, paving the ground for further investigation to choose drug products to substitute currently marketed ones.

کلیدواژه‌ها English

Transdermal Drug Delivery
Noisome
Generalized anxiety disorder
Panic Disorder
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