Delivery of Biological Therapeutics: Using Engineered Particles and Novel Deliver

以安全有效的方式将有希望的生物疗法转移到人体中所需的位置 时尚是医学界的关键挑战之一。许多不同的疾病状态现在都是目标 用于生物制剂的治疗，包括肿瘤学、自身免疫、炎症、代谢、心血管、 神经科和眼科。此外，预计生物疗法将发挥主要作用。 在治疗疼痛中的作用以及在抗感染、抗细菌、抗病毒和抗真菌方面的用途 治疗。然而，尽管有机会，但仍有许多重大障碍阻碍着 充分发挥生物疗法和疫苗的潜力，包括：i)需要显著 改善循环时间；ii)无法使用简单的注射或口服来调整药代动力学； 三)无法通过肺部途径输送生物制品；四)许多生物制品无法进入 细胞内靶点；以及v)无法将生物药物输送到血运不良的组织。在此，我 建议发展新兴的自上而下的粒子制造技术，以制造二维阵列和 形状特定的微米和纳米颗粒的自由流动粉末，由几乎纯的 生物分子。使用基于图案化薄膜的冷冻干燥工艺，具有非常高的比率 在热和质量传输方面，由生物分子组成的颗粒的固态溶液将是 合成以控制模制颗粒的溶解速度或生物颗粒的溶解速度 粒子内的分子将被释放。此外，我建议利用独特的二维 形状可控生物疗法的阵列形式和自由流动粉末的形成 疫苗将开发三种新剂型，包括：i)通过高浓度分散体递送 (替代溶液)；ii)吸入肺部给药；以及iii)新颖的内窥镜和血管内 使用纳米颗粒介导的离子电泳法/电泳法传递的医疗设备 从生物制品到血运不良的组织。

Getting promising biological therapeutics to the desired location in the body in a safe and effective fashion is one of the key challenges in medicine. Many different disease states are now being targeted for treatment with biologicals including oncology, autoimmune, inflammatory, metabolic, cardiovascular, neurological, and ophthalmologic. In addition, it is anticipated that biological therapies will play a major role in the treatment of pain and for the use in anti-infective, anti-bacterial, anti-viral and anti-fungal treatments. However, despite the opportunity, there are significant road blocks that stand in the way to realizing the full potential of biological therapeutics and vaccines including: i) the need to dramatically improve circulation times; ii) the inability to tailor pharmacokinetics using simple injections or oral delivery; iii) the inability to deliver biologicals via pulmonary routes; iv) the inability of many biologicals to access intracellular targets; and v) the inability to deliver biologicals to poorly-vascularized tissues. Herein I propose to evolve emerging top-down particle fabrication technologies to make 2-dimensional arrays and free flowing powders of shape specific micro- and nano-particles that are comprised of almost pure biological molecules. Using patterned thin film based lyophilization processes that have very high rates of thermal and mass transport, ¿solid state solutions¿ of particles comprised of biological molecules will be synthesized to control how quickly the molded particles will dissolve or how quickly the biological molecules within the particles will be released. In addition, I propose to exploit the unique 2-dimensional array format and the formation of free flowing powders of shape controlled biological therapeutics and vaccines to develop three novel dosage forms including: i) delivery via highly concentrated dispersions (alternative to solutions); ii) pulmonary delivery via inhalation; and iii) novel endoscopic and intravascular medical devices which use nanoparticle mediated ionotophoretic / electrophoretic methods to deliver biologicals to poorly vascularized tissues.