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：
8435333
负责人：
KINAM PARK
金额：
$ 28.07万
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 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8435333
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.

描述（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。各种抗体治疗癌症的好处是众所周知的。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（数周至数月）递送蛋白质药物的药物递送制剂将为递送多种蛋白质药物提供基本工具，从而对该领域产生持续而强大的影响。微米尺寸的颗粒制剂（“微粒”）已被广泛研究用于低分子量药物的长期递送，但它们在蛋白质药物方面的成功极为有限。目前乳剂法制备的颗粒制剂存在粒径不均匀、载药量低、初始突释率高、药物释放不完全、难以放大生产等不足。本研究的目标是利用最近开发的水凝胶模板方法来配制均质微粒，用于临床应用的长期（1个月~3个月）递送蛋白质药物。该提案的假设是，基于水凝胶模板的制造通过在微囊化过程中将蛋白质/PLGA 混合物限制在水凝胶模板的微孔中，提供具有可预测释放曲线的高载药量颗粒。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/微结构的蛋白质装载和释放特性； (iii)通过体内动物研究和体外细胞培养方法评价治疗效果。水凝胶模板方法的创新在于，只需将模板溶解在水中即可收获在水凝胶模板的各个孔内制造的微粒。目前，没有其他制造方法允许如此简单地收获形成的微粒。该方法简单，可以轻松放大生产以用于临床应用。这项研究的意义在于，水凝胶模板方法提供了一种精确制造具有蛋白质药物递送预定特性的微粒的新通用方法。水凝胶模板方法是一种可应用于所有类型药物的使能技术，使得开发各种蛋白质药物的临床有用制剂变得容易。