Diou O, Greco S, Beltran T, Lairez D, Authelin J-R, Bazile D
Sanofi Research and Development, Lead Generation to Candidate Realization Platform, 13 Quai Jules Guesde, 94403, Vitry-sur-Seine, France.
Laboratoire Léon Brillouin, CEA Saclay, Gif-sur-Yvette Cedex, 91191, France.
Pharm Res. 2015 Oct;32(10):3188-200. doi: 10.1007/s11095-015-1696-0. Epub 2015 Apr 22.
To study the impact of the size and the structure of the nano-assembly on the drug/particle association, determining the intrinsic partition coefficient, in order to better master the encapsulation and release properties of the carrier.
An experimental methodology is proposed to characterize the drug/nanoparticle association by mean of a partition coefficient between the PLA-PEG nanoparticles and the suspending aqueous medium, referred to as Kp. The determination was made from apparent values (referred to as Kp (ap)) measured in the presence of solubilizing agents (albumin and hydroxypropyl-βcyclodextrin) and extrapolation to zero concentration. The structure of nanoparticles was investigated by Transmission Electron Microscopy and static light scattering.
Depending on the manufacturing process and the PEG length of the copolymer, the nanoparticles structured either as aggregates of copolymer chains or micelles exhibiting significantly different Kp values.
The methodological tool described here showed that the difference in cabazitaxel/nanoparticle association between aggregates and micelles could be attributed to the difference in PLA-PEG chains packing.
研究纳米聚集体的尺寸和结构对药物/颗粒结合的影响，确定固有分配系数，以便更好地掌握载体的包封和释放特性。
提出一种实验方法，通过聚乳酸-聚乙二醇（PLA-PEG）纳米颗粒与悬浮水介质之间的分配系数（称为Kp）来表征药物/纳米颗粒的结合。该测定是根据在增溶剂（白蛋白和羟丙基-β-环糊精）存在下测得的表观值（称为Kp(ap)）并外推至零浓度进行的。通过透射电子显微镜和静态光散射研究纳米颗粒的结构。
根据制造工艺和共聚物的聚乙二醇长度，纳米颗粒可构成共聚物链的聚集体或胶束，其Kp值有显著差异。
此处描述的方法工具表明，卡巴他赛/纳米颗粒在聚集体和胶束之间的结合差异可归因于PLA-PEG链堆积的差异。
