In last few years, therapeutic peptides/proteins are rapidly growing in drug market considering their higher efficiency and lower toxicity than chemical drugs. However, the administration of therapeutic peptides/prote...In last few years, therapeutic peptides/proteins are rapidly growing in drug market considering their higher efficiency and lower toxicity than chemical drugs. However, the administration of therapeutic peptides/proteins is mainly limited in parenteral approach. Oral therapy which was hampered by harsh gastrointestinal environment and poorly penetrating epithelial barriers often results in low bioavailability(less than 1%–2%). Therefore, delivery systems that are rationally designed to overcome these challenges in gastrointestinal tract and ameliorate the oral bioavailability of therapeutic peptides/proteins are seriously promising. In this review, we summarized various multifunctional delivery systems, including lipid-based particles, polysaccharide-based particles, inorganic particles, and synthetic multifunctional particles that achieved effective oral delivery of therapeutic peptides/proteins.展开更多
Peptide drugs play an important role in diabetes mellitus treatment.Oral administration of peptide drugs is a promising strategy for diabetes mellitus because of its convenience and high patient compliance compared to...Peptide drugs play an important role in diabetes mellitus treatment.Oral administration of peptide drugs is a promising strategy for diabetes mellitus because of its convenience and high patient compliance compared to parenteral administration routes.However,there are a series of formidable unfavorable conditions present in the gastrointestinal(GI)tract after oral administration,which result in the low oral bioavailability of these peptide drugs.To overcome these challenges,various nanoparticles(NPs)have been developed to improve the oral absorption of peptide drugs due to their unique in vivo properties and high design flexibility.This review discusses the unfavorable conditions present in the GI tract and provides the corresponding strategies to overcome these challenges.The review provides a comprehensive overview on the NPs that have been constructed for oral peptide drug delivery in diabetes mellitus treatment.Finally,we will discuss the rational application and give some suggestions that can be utilized for the development of oral peptide drug NPs.Our aim is to provide a systemic and comprehensive review of oral peptide drug NPs that can overcome the challenges in GI tract for efficient treatment of diabetes mellitus.展开更多
目的研究在不同钙离子存在条件下二氧化硅的性质和对蛋白包裹能力有无变化,来确定其是否有作为口服载体的性能。方法研究包裹多肽二氧化硅纳米颗粒的制备、包裹多肽二氧化硅纳米颗粒的体外释放实验、包裹不同多肽的二氧化硅纳米颗粒的...目的研究在不同钙离子存在条件下二氧化硅的性质和对蛋白包裹能力有无变化,来确定其是否有作为口服载体的性能。方法研究包裹多肽二氧化硅纳米颗粒的制备、包裹多肽二氧化硅纳米颗粒的体外释放实验、包裹不同多肽的二氧化硅纳米颗粒的表征、包裹含有不同量的氯化钙和不同结构的多肽二氧化硅纳米颗粒性能。结果以含有His标签的增强绿色荧光蛋白(enhance green fluorescent portein,EGFP;PI 5.99)为模型,采用反相微乳液体系中加入适量氯化钙,钙离子既和二氧化硅纳米粒子内部的氧原子形成离子键,又和His标签形成络合作用,这样就将蛋白质固定在二氧化硅纳米粒子内部,经过多次洗涤泄露较少。酶切、加热、尿素变性等试验均显示其具有良好的稳定性。结论通过在传统的反相微乳液体系中加入适量的钙离子,就可以达到良好的包裹效果,且其在酸性条件下不易释放,而在碱性条件则相对容易释放,符合用于口服药物载体的基本要求。展开更多
基金financially supported by the CAMS Innovation Fund for Medical Sciences(CAMS-2017-12M-1–011,China)National Natural Science Foundation of China(81373342)+1 种基金the Fundamental Research Funds for the Central Universities and PUMC Youth Fund(2017350003,China)PUMC Basic Fund(2018PT35002,China)
文摘In last few years, therapeutic peptides/proteins are rapidly growing in drug market considering their higher efficiency and lower toxicity than chemical drugs. However, the administration of therapeutic peptides/proteins is mainly limited in parenteral approach. Oral therapy which was hampered by harsh gastrointestinal environment and poorly penetrating epithelial barriers often results in low bioavailability(less than 1%–2%). Therefore, delivery systems that are rationally designed to overcome these challenges in gastrointestinal tract and ameliorate the oral bioavailability of therapeutic peptides/proteins are seriously promising. In this review, we summarized various multifunctional delivery systems, including lipid-based particles, polysaccharide-based particles, inorganic particles, and synthetic multifunctional particles that achieved effective oral delivery of therapeutic peptides/proteins.
基金supported by the National Natural Science Foundation of China(32071391,21905283,31771095,21875254,52073287 and 22075289)the Fundamental Research Funds for the Central Universities(06500230)the Beijing Nova Program(Z201100006820140).
文摘Peptide drugs play an important role in diabetes mellitus treatment.Oral administration of peptide drugs is a promising strategy for diabetes mellitus because of its convenience and high patient compliance compared to parenteral administration routes.However,there are a series of formidable unfavorable conditions present in the gastrointestinal(GI)tract after oral administration,which result in the low oral bioavailability of these peptide drugs.To overcome these challenges,various nanoparticles(NPs)have been developed to improve the oral absorption of peptide drugs due to their unique in vivo properties and high design flexibility.This review discusses the unfavorable conditions present in the GI tract and provides the corresponding strategies to overcome these challenges.The review provides a comprehensive overview on the NPs that have been constructed for oral peptide drug delivery in diabetes mellitus treatment.Finally,we will discuss the rational application and give some suggestions that can be utilized for the development of oral peptide drug NPs.Our aim is to provide a systemic and comprehensive review of oral peptide drug NPs that can overcome the challenges in GI tract for efficient treatment of diabetes mellitus.
文摘目的研究在不同钙离子存在条件下二氧化硅的性质和对蛋白包裹能力有无变化,来确定其是否有作为口服载体的性能。方法研究包裹多肽二氧化硅纳米颗粒的制备、包裹多肽二氧化硅纳米颗粒的体外释放实验、包裹不同多肽的二氧化硅纳米颗粒的表征、包裹含有不同量的氯化钙和不同结构的多肽二氧化硅纳米颗粒性能。结果以含有His标签的增强绿色荧光蛋白(enhance green fluorescent portein,EGFP;PI 5.99)为模型,采用反相微乳液体系中加入适量氯化钙,钙离子既和二氧化硅纳米粒子内部的氧原子形成离子键,又和His标签形成络合作用,这样就将蛋白质固定在二氧化硅纳米粒子内部,经过多次洗涤泄露较少。酶切、加热、尿素变性等试验均显示其具有良好的稳定性。结论通过在传统的反相微乳液体系中加入适量的钙离子,就可以达到良好的包裹效果,且其在酸性条件下不易释放,而在碱性条件则相对容易释放,符合用于口服药物载体的基本要求。
