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Hydrogel template method for protein microencapsulation

蛋白质微囊化的水凝胶模板法

基本信息

批准号：
8792537
负责人：
KINAM PARK
金额：
$ 28.87万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-03-01 至 2016-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8792537
关键词：
Affect Animals Antibodies Blood Circulation Cardiovascular Diseases Cell Culture Techniques Core Protein Development Disease Drug Delivery Systems Drug Formulations Emulsions Erythropoietin Excision Genetic Engineering Glycolates Goals Half-Life Harvest Hydrogels In Vitro Individual Injection of therapeutic agent Kinetics Laboratories Longitudinal Studies Malignant Neoplasms Methodology Methods Microencapsulations Molecular Weight Operative Surgical Procedures Particle Size Particulate Pharmaceutical Preparations Process Production Property Proteins Recording of previous events Research Shapes Solvents Somatropin Structure Techniques Testing Therapeutic Therapeutic Effect Treatment Efficacy Water base capsule clinical application evaporation in vivo innovation nanofabrication nanosized particle protein structure scale up solvent extraction success tool

项目摘要

DESCRIPTION (provided by applicant): Protein drugs have proven themselves as highly important therapeutic drugs in treating various diseases, including cancer and cardiovascular diseases. The benefits of various antibodies for treating cancers are well known. One of the major problems with protein drugs is their short half life in blood circulation. The drug delivery formations that can deliver protein drugs for long-term, ranging from weeks to months, will provide a basic tool for delivering a variety of protein drugs, enabling the sustained and powerful impact to the field. Particulate formulations in the micro-sizes ("microparticles") have been extensively studied for long-term delivery of low molecular weight drugs, but their success with protein drugs has been extremely limited. The deficiencies of the current particulate formulations prepared by the emulsion methods include heterogeneous particle size, low drug loading capacity, high initial burst release, incomplete drug release, and difficulty in scaling-up production. The goal of this research is to use the recently developed hydrogel template approach to formulate homogeneous microparticles for long-term (1 month ~ 3 months) delivery of protein drugs for clinical applications. The hypothesis in this proposal is that the hydrogel template-based fabrication provides particles of high drug loading with predictable release profiles by confining the protein/PLGA mixture to the micro wells in a hydrogel template during the microencapsulation process. The specific aims of this project are: (i) to fabricate homogeneous nan0/micro structures using hydrogel templates; (ii) to characterize protein loading and release properties of nan0/micro structures; and (iii) to evaluate therapeutic effects by in vivo animal study and in vitro cell culture method. The innovation in the hydrogel template approach is that microparticles, which are fabricated inside individual wells of the hydrogel template, can be harvested by simply dissolving the template in water. Currently, no other fabrication methods allow such an easy way of harvesting the formed microparticles. The simplicity in the method allows easy scale-up production for clinical applications. The significance of this research is that the hydrogel template approach provides a new general method of precise fabrication of microparticles with predefined properties for protein drug delivery. The hydrogel template method is an enabling technique that can be applied to all types of drugs, making it easy to develop clinically useful formulations for various protein drugs.

说明（申请人提供）：蛋白质药物已被证明是治疗各种疾病（包括癌症和心血管疾病）的非常重要的治疗药物。用于治疗癌症的各种抗体的益处是众所周知的。蛋白质药物的主要问题之一是它们在血液循环中的半衰期短。能够长期（从数周到数月）递送蛋白质药物的药物递送形成物将为递送各种蛋白质药物提供基本工具，从而能够对该领域产生持续而强大的影响。已经广泛研究了微米尺寸的颗粒制剂（“微粒”）用于长期递送低分子量药物，但是它们在蛋白质药物方面的成功非常有限。目前通过乳液方法制备的颗粒制剂的缺陷包括不均匀的粒径、低载药量、高初始突释、不完全药物释放和难以放大生产。本研究的目的是利用近年来发展起来的水凝胶模板法制备均一的蛋白质药物缓释微球，并将其应用于临床。该提议中的假设是，基于水凝胶模板的制造通过在微胶囊化过程中将蛋白质/PLGA混合物限制在水凝胶模板中的微孔威尔斯中，提供具有可预测释放曲线的高药物负载的颗粒。该项目的具体目标是：（i）使用水凝胶模板制造均匀的纳米/微米结构;（ii）表征纳米/微米结构的蛋白质负载和释放特性;以及（iii）通过体内动物研究和体外细胞培养方法评估治疗效果。水凝胶模板方法的创新在于，可以通过简单地将模板溶解在水中来收获在水凝胶模板的各个威尔斯孔内制造的微粒。目前，没有其他制造方法允许这样一种简单的方式来收获所形成的微粒。该方法的简单性允许用于临床应用的容易的规模化生产。这项研究的意义在于，水凝胶模板方法提供了一种新的通用方法，用于精确制造具有预定义性质的蛋白质药物递送微粒。水凝胶模板法是一种可行的技术，可应用于所有类型的药物，使其易于开发各种蛋白质药物的临床有用制剂。