纳米制剂

1 nm = ? m
Atom Molecular
Nanoparticle
Macroscopic objects
0.1-1.0 nm
1-100 nm
>1 mm
Properties surface effect
of Nanoparticles：
small size effect quantum effect




ζ电位是双电层切平面处的电位，是衡量纳 米药物稳定性的标准之一，绝对值越高，纳 米药物越稳定，用激光多普勒电泳法测定。 electrostatic stabilization and steric stabilization :ζ ≥ 20 mV； electrostatic stabilization :ζ ≥ 30 mV
2.The physical stability of nano-drug

Stability of Nano-drug ：physical, chemical and biological stability
物理化学 的角度
sedimentation aggregation crystal growth crystalline state change
1.Formulations affect the stability


Nano-drug are widely used in oral, eye, lung and skin delivery systems. They have same phenomenon of instability for different forms, such as precipitation, agglomeration and crystal growth, but these phenomenon have different effect on clinical. Moreover, the choice of stabilizer are also closely related to formulations.

Flocculant In the flocculant, particle begins sedimentation in the form of loose flock. This loose flock contains a large dispersion medium. Simple agitation or shaking can be easily dispersed again, resume its suspended state quickly, thus overcoming the problem to restore suspended state
例子： “开放式絮凝物”结构而获得稳定的纳米
混悬剂



将牛血清白蛋白溶于pH 为7.4 的磷酸盐缓冲液 然后通过不锈钢针头从10 cm 高处滴加到旋转的不锈钢圆 盘（内装干冰）上，液滴接触圆盘后形成薄层， 冻结后将 冻结物转入液氮中继续冻结 最后减压、冷冻干燥即获得长径比（aspect ratio）约24 的 牛血清白蛋白纳米棒。 在-80℃条件下将牛血清白蛋白纳米棒粉末和七氟丙烷 （HFA-227）混合，超声，装入压力容器中，制成压力定 量吸入气雾剂。 该制剂形成的絮状物室温放置一年稳定，具有很好的稳定 性。
纳米制剂.ppt 52页 内容提供方 : zw4044 大小 : 202 kb 字数 :约1.07万字 发布时间 : 2018-03-24 浏览人气 : 1635 下载次数 :仅上传者可见 收藏次数 : 0 需要金币 : *** 金币 (10金币=人民币1元) 纳米制剂.ppt 关闭预览 想预览更多内容,点击免费在线预览全文 免费在线预览全文 纳米制剂 stability of nano-preparation 纳米药物 nano-drug 定义 将药物的微粒或者将药物吸附包裹在特定载体中,制成纳米尺寸范围内的微粒,然后以其为基础制成不同种类的剂型。 comparison ethnodrug 药物微粒大、表面反应活性低、活性中心少、催化效率低、吸附能力弱,并且对人体的毒性较大,疗效却不佳,且存在严重的量效效应,即疗效—剂量依赖关系 adhesiveness change mechanism of membrane transport controlled release:the use of carrier material, can slow dissolution the stability of nano-preparation nanomedicine crystal stability is affected by many factors : formulation types dry powder, nano-suspension dispersion medium aqueous and non-aqueous route of administration oral, inhalation, intravenous injection , production technology "top-down" and "bottom-up" the nature of the drug itself small molecules and biological macromolecules 1.formulations affect the stability nano-drug are widely used in oral, eye, lung and skin delivery systems. they have same phenomenon of instability for diffe
2.2.2 Steric stabilization

Content: Adsorbed on the particles surface of the polymer can hinder the particles closed to each other from space, thereby hampering their aggregation
2.2.1 Electrostatic repulsion


DLVO（Derjaguin-Landau-Verwey-Overbeek）
In the medium, the force among particles can be divided to electrostatic repulsion and van der Waalsforces.Crossover of particle surface double layer lead to repulsion between the particles.The van der Waals forces between molecules constitute attraction between particles. The distance between particle and particle size effects attraction. Particle size, inter-particle distance, ζ potential, ion concentration effects repulsive.
Comparison

Ethnodrug 药物微粒大、表面反应活性低、活性中心 少、催化效率低、吸附能力弱，并且对人 体的毒性较大，疗效却不佳，且存在严重 的量效效应，即疗效—剂量依赖关系
Nano-drug (Features) ：

Solubilization：reduce particle size、control of particle size distribution，it can increased solubility of the drug, the drug easily absorbed
Stability of nano-preparation

纳米粒子（Nanoparticle）：
Also called ultrafine particles, 1 ~ 100 nm particles or tiny structures in atomic clusters and macroscopic objects at the junction of the transition region.
2.1 Sedimentation
Nano-drug generally have three kinds of precipitation: agglomeration, loose aggregates and open floc. Under the action of gravity, the process of particles directional movement and makes the dispersion happened phase separation is known as sedimentation. Stokes公式： V=2 r² （ρ1-ρ2） g/（9η） 式中，V 为微粒沉降速度，r 为微粒半径，ρ1、ρ2 分别为微粒和分散介质的密度，g 为重力加速度， η为分散介质黏度。

V=2 r² （ρ1-ρ2） g/（9η）
由Stokes 公式可见，微粒沉降速度与微粒半径平 方、微粒与分散介质的密度差成正比，与分散介 质的黏度成反比。 Primary method of reducing nano-drug sedimentation ： ① Reduce particle radius ； ② Reducing the density difference between the solid particles and the dispersion medium ； ③ Increase the viscosity of the dispersion medium
The stability of nano-preparation
Nanomedicine crystal stability is affected by many factors :
formulation types(dry powder, nano-suspension ) dispersion medium (aqueous and non-aqueous) route of administration (oral, inhalation, intravenous injection), production technology ("top-down" and "bottom-up") the nature of the drug itself (small molecules and biological macromolecules)
Electrostatic repulsion

Nano-drug Steric stabilization

Evaluation nano-drug dispersion and stability of aggregation important parameter is the particle size and distribution Particle size and distribution ：dynamic light scattering（DLS）、 laser diffraction （LD）、Coulter Particle morphology ：Scanning electron microscopy 、 Transmission electron microscopy
The drug is dissolved or dispersed in nanoparticles. Like Liposomes、Polymeric micelles.
The new nanodrugs:
The use of nano-structures or nano-features, found some treatment or diagnosis drug of efficiency and low toxicity based on new nano-particles



此方法制备的纳米棒相互接触点间的范德 华力较强，加入氢氟烷烃时，纳米棒间能 相互锁定形成一个个开放的环状结构，抑 制絮凝物结构的破坏。 另外，由于纳米棒具有很高的长径比，所 形成的絮凝物比球状结构形成的絮凝物密 度低，能更好地填充整个制剂空间而更稳 定。综上原因，使得这种“开放式絮凝物” 可以有效地克服粒子沉降问题。

Targeted release：vector

stabilize efficacy of drug
Adhesiveness Change mechanism of membrane transport

Controlled release：Leabharlann he use of carrier
material, can slow dissolution
2.2 Aggregation


Large dispersion → surface free energy → aggregation → rapid subsidence，crystal growth → Uneven distribution of drug dose，capillary clogging（injection） Stabilizers fully wet the particle surface, forming an electrostatic repulsion to produce high barrier, inhibit aggregation.
superior performance
纳米药物(nano-drug)

定义 将药物的微粒或者将药物吸附包裹在特 定载体中，制成纳米尺寸范围内的微粒， 然后以其为基础制成不同种类的剂型。
Classification of nano-drug
Nanocarriers drugs:

nano-drug