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Stimuli-responsive In situ gelling system for nose-to-brain drug delivery
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-07-31 , DOI: 10.1016/j.jconrel.2020.07.044 Mukta Agrawal 1 , Shailendra Saraf 2 , Swarnlata Saraf 2 , Sunil K Dubey 3 , Anu Puri 4 , Umesh Gupta 5 , Prashant Kesharwani 6 , V Ravichandiran 7 , Pramod Kumar 8 , V G M Naidu 9 , Upadhyayula Suryanarayana Murty 10 , Ajazuddin 1 , Amit Alexander 11
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2020-07-31 , DOI: 10.1016/j.jconrel.2020.07.044 Mukta Agrawal 1 , Shailendra Saraf 2 , Swarnlata Saraf 2 , Sunil K Dubey 3 , Anu Puri 4 , Umesh Gupta 5 , Prashant Kesharwani 6 , V Ravichandiran 7 , Pramod Kumar 8 , V G M Naidu 9 , Upadhyayula Suryanarayana Murty 10 , Ajazuddin 1 , Amit Alexander 11
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The diagnosis and treatment of neurological ailments always remain an utmost challenge for research fraternity due to the presence of BBB. The intranasal route appeared as an attractive and alternative route for brain targeting of therapeutics without the intrusion of BBB and GI exposure. This route directly and effectively delivers the therapeutics to different regions of the brain via olfactory and trigeminal nerve pathways. However, shorter drug retention time and mucociliary clearance curtail the efficiency of the intranasal route. The mucoadhesive gel overthrow the limitations of direct nose-to-brain delivery by not only enhancing nasal residence time but also minimizing the mucociliary clearance and enzymatic degradation. This delivery system further improves the nasal absorption as well as bioavailability of drugs in the brain. The mucoadhesive gel is a controlled and sustained release system that facilitates the absorption of various proteins, peptides and other larger lipophilic and hydrophilic moieties. Owing to multiple benefits, gelling system has been widely explored to target the brain via nasal route. However, very few review works are reported which explains the application of nasal gel for brain delivery of CNS acting moieties. Hence, in this piece of work, we have initially discussed the global statistics of neurological disorders reported by WHO and other reputed organizations, nasal anatomy, mechanism and challenges of nose-to-brain drug delivery. The work mainly focused on the use of different stimuli-responsive polymers, specifically thermoresponsive, pH-responsive, and ion triggered systems for the development of an effective and controlled dosage form, i.e., nasal gel for brain targeting of bioactives. We have also highlighted the origin, structure, nature and phase transition behavior of the smart polymers found suitable for nasal administration, including poloxamer, chitosan, EHEC, xyloglucan, Carbopol, gellan gum and DGG along with their application in the treatment of neurological disorders. The article is aimed to gather all the information of the past 10 years related to the development and application of stimuli-responsive nasal gel for brain drug delivery.
中文翻译：
用于鼻到脑药物输送的刺激响应原位凝胶系统
由于 BBB 的存在，神经系统疾病的诊断和治疗始终是研究界面临的最大挑战。鼻内途径似乎是一种有吸引力的大脑靶向治疗的替代途径，且不会干扰血脑屏障和胃肠道暴露。该途径通过嗅觉和三叉神经通路直接有效地将治疗药物传递到大脑的不同区域。然而，较短的药物保留时间和粘液纤毛清除降低了鼻内途径的效率。粘膜粘附凝胶不仅可以延长鼻腔停留时间，还可以最大限度地减少粘膜纤毛清除和酶降解，从而克服了直接从鼻子到大脑输送的局限性。该输送系统进一步改善了药物在鼻腔的吸收以及大脑中的生物利用度。粘膜粘附凝胶是一种受控和持续释放系统，有助于各种蛋白质、肽和其他较大的亲脂性和亲水性部分的吸收。由于具有多种优点，凝胶系统已被广泛探索通过鼻腔途径靶向大脑。然而，解释鼻凝胶在中枢神经系统作用部分的脑递送中的应用的综述工作却很少报道。因此，在这项工作中，我们初步讨论了世界卫生组织和其他知名组织报告的神经系统疾病的全球统计数据、鼻腔解剖结构、鼻子到大脑药物输送的机制和挑战。这项工作主要集中于使用不同的刺激响应聚合物，特别是热响应、pH 响应和离子触发系统来开发有效且受控的剂型，即用于脑靶向生物活性物质的鼻凝胶。 我们还重点介绍了适合鼻腔给药的智能聚合物的起源、结构、性质和相变行为，包括泊洛沙姆、壳聚糖、肠出血性大肠杆菌、木葡聚糖、卡波普、结冷胶和 DGG，以及它们在治疗神经系统疾病中的应用。本文旨在收集过去10年来与刺激响应鼻凝胶用于脑部给药的开发和应用相关的所有信息。
更新日期：2020-07-31
中文翻译：
用于鼻到脑药物输送的刺激响应原位凝胶系统
由于 BBB 的存在，神经系统疾病的诊断和治疗始终是研究界面临的最大挑战。鼻内途径似乎是一种有吸引力的大脑靶向治疗的替代途径，且不会干扰血脑屏障和胃肠道暴露。该途径通过嗅觉和三叉神经通路直接有效地将治疗药物传递到大脑的不同区域。然而，较短的药物保留时间和粘液纤毛清除降低了鼻内途径的效率。粘膜粘附凝胶不仅可以延长鼻腔停留时间，还可以最大限度地减少粘膜纤毛清除和酶降解，从而克服了直接从鼻子到大脑输送的局限性。该输送系统进一步改善了药物在鼻腔的吸收以及大脑中的生物利用度。粘膜粘附凝胶是一种受控和持续释放系统，有助于各种蛋白质、肽和其他较大的亲脂性和亲水性部分的吸收。由于具有多种优点，凝胶系统已被广泛探索通过鼻腔途径靶向大脑。然而，解释鼻凝胶在中枢神经系统作用部分的脑递送中的应用的综述工作却很少报道。因此，在这项工作中，我们初步讨论了世界卫生组织和其他知名组织报告的神经系统疾病的全球统计数据、鼻腔解剖结构、鼻子到大脑药物输送的机制和挑战。这项工作主要集中于使用不同的刺激响应聚合物，特别是热响应、pH 响应和离子触发系统来开发有效且受控的剂型，即用于脑靶向生物活性物质的鼻凝胶。 我们还重点介绍了适合鼻腔给药的智能聚合物的起源、结构、性质和相变行为，包括泊洛沙姆、壳聚糖、肠出血性大肠杆菌、木葡聚糖、卡波普、结冷胶和 DGG，以及它们在治疗神经系统疾病中的应用。本文旨在收集过去10年来与刺激响应鼻凝胶用于脑部给药的开发和应用相关的所有信息。
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