Hydrogel template method for protein microencapsulation

蛋白质微囊化的水凝胶模板法

• 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
• 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

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多种疾病的重要治疗药物，包括癌症和心血管疾病。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很短。能够长期递送蛋白质药物的药物输送编队，从数周到数月，将为递送各种蛋白质药物提供基本工具，使其能够对该领域产生持续和强大的影响。微尺寸的微粒制剂（“微粒”）已经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非常有限。目前采用乳化法制备的颗粒制剂存在粒径不均、载药量低、初爆释放高、释放不完全、规模化生产困难等不足。本研究的目的是利用最近开发的水凝胶模板方法，形成均匀的微颗粒，长期（1个月~ 3个月）递送蛋白质药物，用于临床应用。本提案的假设是，在微胶囊化过程中，基于水凝胶模板的制备通过将蛋白质/PLGA混合物限制在水凝胶模板的微孔中，提供了具有可预测释放谱的高载药颗粒。该项目的具体目标是：(i)使用水凝胶模板制造均匀的纳米/微观结构；（ii）表征纳米/微观结构的蛋白质装载和释放特性；（三）通过体内动物实验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之处在于，在水凝胶模板的单个孔内制造的微粒可以通过简单地将模板溶解在水中来收集。目前，还没有其他制造方法可以如此简单地收集形成的微粒。该方法简单，便于临床应用的规模化生产。本研究的意义在于，水凝胶模板方法提供了一种新的通用方法来精确制造具有预定义特性的用于蛋白质药物递送的微粒。水凝胶模板法是一种可以应用于所有类型药物的使能技术，可以很容易地为各种蛋白质药物开发临床有用的配方。