Polymeric nanoparticles: A promising strategy for treatment of Alzheimer's disease

الملخص: تطور مرض ألزهايمر كنتيجة لتكوين علامتين رئيسيتين، والتي تتضمن تشكيل طفيليات البيتا-أميلويد خارج الخلو وفرط فسفرة بروتين الـ تاو، مما يؤدي إلى تشكل عقد عصبية متعرجة. تؤدي هاتان العلامتان إلى فقدان التآزر بين الخلايا العصبية، وتلف الخلايا العصبية، وتطوير الالتهاب العصبي والإجهاد التأكسدي، مما يعزز تقدم المرض. لذلك، يهدف علاج مرض ألزهايمر إلى القضاء على هذه العلامات الرئيسية لمنع تقدم المرض وتقليل الأعراض. ومع ذلك، فإن العلاج الحالي المتوفر في السوق يوفر تخفيفا أعراضيا بدلا من معالجة السبب الأساسي للمرض. ويعزى هذا إلى الطبيعة المقيدة لحاجز الدماغ-الدم التي تعوق دخول الأدوية، مما يؤثر على فعالية الدواء وقابليته للامتصاص. يركز الباحثون على تطوير طرق علاجية جديدة يمكن أن تتجاوز حاجز الدماغ-الدم، لتوفير توصيل الدواء إلى الموقع المحدد مع أقصى قابلية امتصاص ممكنة وأقل آثار جانبية. من بين الاستراتيجيات العلاجية الجديدة المكتشفة هي استخدام البيولوجيات كأضداد أحادية النسيلة. واقترح اداكونوماب مرشحا قويا لعلاج مرض ألزهايمر وحصل على موافقة مسرعة من إدارة الغذاء والدواء، ومع ذلك، فإن مخاوف السلامة قد تحول دون استخدامه في المستقبل. وبالتالي، تشكل التقنية النانوية عصرا جديدا لعلاج مرض ألزهايمر، نظرا للسمات المميزة التي توفرها جزيئات النانو من حيث اجتياز حاجز الدماغ-الدم بسبب حجمها الصغير، وتعزيز الخصائص الدوائية للأدوية وتوصيل الدواء المستهدف. تدرس جزيئات النانو البوليمرية بشكل موسع في الوقت الراهن، نظرا لسهولة وبساطة طريقة إنتاجها، والتحلل البيولوجي، والتوافق البيولوجي والهيكل الفريد الذي يوفر وعاء مرن يمكن تعديله بسهولة لتحقيق الخصائص الفيزيوكيميائية المرغوبة. وبالتالي، سيتم مناقشة أنواع مختلفة من جزيئات النانو القائمة على البوليمر في هذه المراجعة، مع تسليط الضوء على الخصائص التي توفرها جزيئات النانو المصنعة والتي تظهر العديد من الفوائد في علاج مرض ألزهايمر. تشمل هذه الخصائص التأثيرات المضادة للأميلويد والمضادة للأكسدة والمضادة للالتهابات. Abstract: Alzheimer's disease (AD), is characterised by two major hallmarks: the formation of extracellular β-amyloid (Aβ) plaques and the hyperphosphorylation of tau protein, thus leading to the formation of neurofibrillary tangles. These hallmarks cause synaptic loss, neuronal damage, and the development of neuroinflammation and oxidative stress, which promote AD progression. Thus, the goal of treating AD is eliminating these hallmarks, to prevent AD progression and decrease symptoms. However, current available therapies provide symptomatic relief rather than treating the underlying cause of the disease, because the restrictive nature of the blood brain barrier (BBB) impedes the entry of drugs, thereby affecting drug efficacy and bioavailability. Researchers are focusing on developing new therapeutic approaches to bypass the BBB, for achieving site-specific drug delivery with the highest possible bioavailability and the lowest adverse effects. Recently explored therapeutic strategies include use of biologic agents such as monoclonal antibodies. Aducanumab, a strong candidate for treating AD, has been granted accelerated Food and Drug Administration approval; however, safety concerns may hinder its future use. Thus, nanotechnological approaches have led to a new era of AD treatment. Nanoparticles (NPs), because of their small particle size, can cross the BBB, thus enhancing drug pharmacokinetic properties and enabling targeted drug delivery. Polymeric NPs have been extensively studied, because of their simple production, biodegradability, biocompatibility, and unique architecture. These NPs provide a flexible vesicle that can be easily tailored to achieve desired physicochemical features. In this review, various types of polymer-based-NPs are discussed, highlighting the properties of fabricated NPs, which have multiple benefits in AD treatment, including anti-amyloid, antioxidant, and anti-inflammatory effects

Ultra-deformable liposomes containing terpenes (terpesomes) loaded fenticonazole nitrate for treatment of vaginal candidiasis: Box-Behnken design optimization, comparative ex vivo and in vivo studies

Fenticonazole nitrate (FTN) is a potent antifungal drug adopted in the treatment of vaginal candidiasis. It has inadequate aqueous solubility hence, novel ultra-deformable liposomes ‘Terpesomes’ (TPs) were developed that might prevail over FTN poor solubility besides TPs might abstain the obstacles of mucus invasion. TPs were assembled by thin-film hydration then optimized by Box Behnken design utilizing terpenes ratio (X1), sodium deoxycholate amount (X2), and ethanol concentration (X3) as independent variable, whereas their impact was inspected for entrapment efficiency (Y1), particle size (Y2), and polydispersity index (Y3). Design Expert® was bestowed to select the optimal TP for more studies. The optimal TP had entrapment efficiency of 62.18 ± 1.39%, particle size of 310.00 ± 8.16 nm, polydispersity index of 0.20 ± 0.10, and zeta potential of −10.19 ± 0.2.00 mV. Elasticity results were greater in the optimal TP related to classical bilosomes. Further, ex vivo permeation illustrated tremendous permeability from the optimal TP correlated to classical bilosomes, and FTN suspension. Besides, in vivo assessment displayed significant inhibition effect in rats from FTN-TPs gel compared to FTN gel. The antifungal potency with undermost histopathological variation was detected in rats treated with FTN-TPs gel. Overall, the acquired findings verified the potency of utilizing FTN-TPs gel for treatment of vaginal candidiasis

Metformin Loaded Zein Polymeric Nanoparticles to Augment Antitumor Activity against Ehrlich Carcinoma via Activation of AMPK Pathway: D-Optimal Design Optimization, In Vitro Characterization, and In Vivo Study

Metformin (MET), an antidiabetic drug, is emerging as a promising anticancer agent. This study was initiated to investigate the antitumor effects and potential molecular targets of MET in mice bearing solid Ehrlich carcinoma (SEC) as a model of breast cancer (BC) and to explore the potential of zein nanoparticles (ZNs) as a carrier for improving the anticancer effect of MET. ZNs were fabricated through ethanol injection followed by probe sonication method. The optimum ZN formulation (ZN8) was spherical and contained 5 mg zein and 30 mg sodium deoxycholate with a small particle size and high entrapment efficiency percentage and zeta potential. A stability study showed that ZN8 was stable for up to three months. In vitro release profiles proved the sustained effect of ZN8 compared to the MET solution. Treatment of SEC-bearing mice with ZN8 produced a more pronounced anticancer effect which was mediated by upregulation of P53 and miRNA-543 as well as downregulation of NF-κB and miRNA-191-5p gene expression. Furthermore, ZN8 produced a marked elevation in pAMPK and caspase-3 levels as well as a significant decrease in cyclin D1, COX-2, and PGE2 levels. The acquired findings verified the potency of MET-loaded ZNs as a treatment approach for BC