生物大分子药物递释系统中材料、结构以及工艺等对药物结构与活性的影响是优化递释系统设计，提高其作用效果以及向临床转化的前提。生物大分子药物分子量大、结构复杂脆弱，变化繁多，且与活性密切相关。为了提高其稳定性、优化体内作用过程和效果，本项目拟发展一系列新型高效生物大分子递释体系。但递释系统的复杂结构及其与药物分子间的相互作用，为其中的药物结构的确认带来了挑战，需要综合化学、物理、生物学以及药理药效、药剂学等多学科的方法，发展针对性的技术平台，才能高效监测不同递释系统中药物分子结构和活性的变化，为递释系统的设计和优化提供依据。本课题拟选取蛋白多肽、抗体、核酸、疫苗四类生物大分子药物中具有代表性的高效递释系统为研究对象，针对这几类药物的不同特点，分析递释系统的材料、结构以及制备工艺等对与生物大分子结构和功能的影响规律，确定结构和活性研究的关键参数，为生物大分子高效递释系统的构建和应用奠定基础。

The design and preparation of advanced drug delivery systems may significantly impact the detailed molecular structure and activities of bio-macromolecules in the system. Peptides, proteins, antibodies as well as various RNA/DNA constructs are being developed as potent drugs and formulated in advanced drug delivery systems for improved efficacy and therapeutic index. However, since they usually have complex and vulnerable three dimensional structures that determine their activities, it’s critically important to monitor structural changes and limit activities loss during BDDS formulation. The task could be highly challenging and requires interdisciplinary knowledge and technical advancements. Our proposal aims to study selected BDDSs that are being developed in this project specifically designed for the delivery and controlled release of protein and peptide drugs, antibody therapeutics, DNA/RNA molecules and vaccines. Since these different drugs have different targets as well as activities mechanisms, we propose to analyze the detailed molecular interactions involved and identify potential vulnerabilities of the drug structure and activity. We hope develop specific methods for monitoring these changes and understanding the cause and effect functions. Such knowledge could be greatly beneficial for the design, optimization, and application of biomacromolecule drug delivery systems (BDDS).