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| 005 | 20260423121329.0 | ||
| 008 | 260411s2025 ua a|||frm||| 000 0 eng d | ||
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_aEG-GICUC _beng _cEG-GICUC _dEG-GICUC _erda |
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| 049 | _aDeposit | ||
| 082 | 0 | 4 | _a615.4 |
| 092 |
_a615.4 _221 |
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| 097 | _aM.Sc | ||
| 099 | _aCai01.08.08.M.Sc.2025.Ho.P | ||
| 100 | 0 |
_aHossam Abdo Ashour AbdelSamad, _epreparation. |
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| 245 | 1 | 2 |
_aA pharmaceutical Study on Anti-Gout Drug / _cby Hossam Abdo Ashour Abdel Samad ; Supervision Prof. Dr. Mohamed Ahmed El-Nabarawi, Prof. Dr. Mahmoud Hassan Teaima, Dr. Samar Fathy El-Habal. |
| 246 | 1 | 5 | _aدراسة صيدلية علي عقار للنقرس |
| 264 | 0 | _c2025. | |
| 300 |
_a141 pages : _billustrations ; _c25 cm. + _eCD. |
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| 336 |
_atext _2rda content |
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| 337 |
_aUnmediated _2rdamedia |
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_avolume _2rdacarrier |
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| 502 | _aThesis (M.Sc)-Cairo University, 2025. | ||
| 504 | _aBibliography: pages 119 -129. | ||
| 520 | 3 | _aObjective of this study was to design, optimize, and evaluate microneedle (MN)-based transdermal delivery systems for the management of gouty arthritis using febuxostat (FBX), either alone or in combination with lornoxicam (LRX). The study aimed to overcome the key limitations of conventional oral formulations of FBX and LRX, including poor aqueous solubility, moderate bioavailability, and systemic adverse effects. This combination enhances the bioavailability of drugs and improves patient compliance compared to traditional tables and gels. Furthermore, it ensures the optimal release kinetics of the drugs. The bioavailability of the Microneedle was evaluated In-Vivo. Gouty arthritis is characterized by an initial inflammatory reaction caused by monosodium urate (MSU) crystals formed in the joints and periarticular tissues. Febuxostat (FBX) is a BCS class II selective xanthine oxidase inhibitor that has a moderate F value (<49%), high permeability, and low solubility. This work created and tested a transdermal delivery system for FBX using chitosan nanoparticles (FBX-Ch NPs) embedded in PVP/Eudragit microneedles (MNs) for the treatment of gout. The optimized MN formulation (M1) displayed good mechanical strength, penetration depth (up to 7 layers of Parafilm), and controlled disintegration after 48 hours. In vitro release was nearly 100% within 48 hours, compared to 55% for pure FBX. Gouty arthritis is defined by an acute inflammatory response triggered by monosodium urate (MSU) crystals deposited in the joints and periarticular tissues. Febuxostat (Feb), a selective xanthine oxidase inhibitor, belongs to BCS class II, showing low solubility and high permeability with a moderate F value (<49%). Lornoxicam (LRX) is a potent nonsteroidal anti-inflammatory drug (NSAID) used extensively to manage pain and inflammatory conditions. However, the drug possesses poor aqueous solubility (i.e., BCS class II). This study presents a microneedle (MN) patch for the co-delivery of Febuxostat and Lornoxicam to tackle the challenges associated with gouty arthritis treatment. The optimized microneedle patch with a biodegradable polyvinyl alcohol (PVA)/polyvinylpyrrolidone(PVP), polyethylene glycol (PEG 400) matrix and chitosan backing worked well both in vitro and in vivo. Lornoxicam and Febuxostat were released at 99% and 100%, respectively, in vitro, within 48 hours. The microneedles were strong enough to withstand 1000g but disintegrated within minutes of skin contact In this chapter, In vivo evaluation in hyperuricemia-induced rat models revealed effective normalization of serum uric acid levels, restoration of xanthine oxidase activity, and marked suppression of inflammatory mediators including NF-κB, TNF-α, IL-1β, and VEGF. Histopathological examinations further confirmed substantial recovery of joint and hepatic architecture, characterized by reduced inflammation, fibrosis, and vascularization. Collectively, these findings establish microneedle technology as a non-invasive, patient-friendly, and superior alternative to conventional oral and topical formulations, offering enhanced bioavailability, sustained therapeutic action, and reduced systemic side effects in the management of gouty arthritis. Ex vivo permeation approached 110 µg/cm² versus 20 µg/cm² for pure FBX. Kinetic modeling revealed non-Fickian diffusion (n = 0.62, R² = 0.991), implying drug diffusion and polymer relaxation. In vivo, microneedle technology effectively normalized blood uric acid levels (****p < 0.0001), reinstated xanthine oxidase activity to baseline, and significantly reduced inflammatory indicators such as NF-κB, IL-1β, TNF-α, and VEGF. In vivo, microneedle technology effectively normalized blood uric acid levels (****p < 0.0001), reinstated xanthine oxidase activity to baseline, and significantly reduced inflammatory indicators such as NF-κB, IL-1β, TNF-α, and VEGF. Histopathological examinations of the joints and liver revealed nearly full recovery, characterized by little fibrosis, inflammation, and vascularization. This surpassed the effects of oral FBX and FBX-Ch NPs. In vivo studies utilizing a hyperuricemia rat model demonstrated that the microneedle patch decreased serum uric acid levels by 85.4% and inhibited xanthine oxidase activity in the serum and liver by 72.4% and 68.3%, respectively. The patch significantly reduced inflammatory markers like MMP-3, CRP, TNF-α, and IL-1β, demonstrating its anti-inflammatory properties. Histopathological analysis showed greater joint and hepatic architecture restoration and inflammation reduction than conventional formulations | |
| 520 | 3 | _aيُعَدّ النقرس المفصلي أحد الأمراض الالتهابية المزمنة الناتجة عن تراكم بلورات اليورات أحادية الصوديوم (MSU) داخل المفاصل والأنسجة المحيطة بها، مما يؤدي إلى نوبات من الالتهاب الحاد، وارتفاع مستويات حمض اليوريك في الدم، وإحداث تغيرات مرضية في أنسجة المفاصل والكبد. وعلى الرغم من توافر بعض العلاجات التقليدية مثل عقار فيبوكسوستات (FBX) الذي يعمل كمثبط انتقائي لإنزيم الزانثين أوكسيديز، وعقار لورنوكسيكام (LRX) الذي يُعَدّ من مضادات الالتهاب غير الستيرويدية (NSAIDs)، إلا أن استخدامهما عبر الطرق الفموية التقليدية يواجه تحديات كبيرة، أهمها ضعف الذوبان المائي، وانخفاض التوافر الحيوي (<49%)، وظهور آثار جانبية جهازية قد تحد من فعاليتهما العلاجية. تهدف هذه الدراسة إلى تصميم وتطوير أنظمة حديثة لتوصيل الدواء عبر الجلد باستخدام تقنية الإبر المجهرية الذائبة (Microneedles) لتحسين فعالية العلاج وتقليل مخاطره. حيث تم تطوير نوعين من التراكيب: الأول يعتمد على تحميل FBX في صورة جسيمات نانوية باستخدام بوليمر الشيتوزان (FBX-Ch NPs) ثم دمجها داخل إبر مجهرية مكونة من بولي فينيل بيروليدون (PVP) وإيودراجيت (Eudragit). أما النوع الثاني فقد اعتمد على تصميم لصقة إبر مجهرية ثنائية الدواء لتحميل كل من FBX و LRX داخل مصفوفة من PVA/PVP مع PEG400، مع استخدام الشيتوزان كدعامة خلفية. تم تقييم خصائص هذه التراكيب من خلال دراسات في المختبر (In vitro) والتي أظهرت انطلاقًا شبه كامل للأدوية (99–100%) خلال 48 ساعة، مقارنة بانطلاق محدود للعقار الخام. | |
| 530 | _aIssues also as CD. | ||
| 546 | _aText in English and abstract in Arabic & English. | ||
| 650 | 0 | _aPharmaceutical industry. | |
| 650 | 0 | _aصناعة الأدوية | |
| 653 | 1 |
_aMicroneedles _aGouty arthritis _apolyvinyl pyrrolidone-K90 _aEudragit RS D30 _aFebuxostat _aSustained release _aChitosan _aLornoxicam _axanthine oxidase activity _aالإبر المجهرية _aالتهاب المفاصل النقرسي |
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| 700 | 0 |
_aMohamed Ahmed El-Nabarawi _ethesis advisor. |
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| 700 | 0 |
_aMahmoud Hassan Teaima _ethesis advisor. |
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| 700 | 0 |
_aSamar Fathy El-Habal _ethesis advisor. |
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| 900 |
_b01-01-2025 _cMohamed Ahmed El-Nabarawi _cMahmoud Hassan Teaima _cSamar Fathy El-Habal _UCairo University _FFaculty of Pharmacy _DDepartment of Pharmaceutics & Industrial Pharmacy |
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| 905 |
_aShimaa _eEman Ghareb |
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| 942 |
_2ddc _cTH _e21 _n0 |
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| 999 | _c179372 | ||