Effect Of Zwitterion Surface Modification On Blood Circulation Time Of Nanocapsules

The surface content of zwitterion on nanocarrier has significant influence on many important properties.It is crucial to clarify the relationship between the surface content of zwitterion and the blood circulation time of nanocarrier for the rational design of nanocarrier with long circulation time and precise delivery characteristics.In this paper,with a mild and simple preparation process,nanocapsule was used as the model of nanocarrier to explore the relationship between the zwitterionic surface content and the blood circulation time of nanocarrier.Firstly,a variety of nanocapsule experimental groups based on phosphorylcholine(PC)and carboxybetaine(CB),two zwitterions,were synthesized by in-situ free radical polymerization,and by regulating the amount of monomer added,the particle size,potential and morphology of the nanocapsules were controlled.Subsequently,using~1H-NMR combining with molecular simulation method,the surface content of zwitterion on the nanocapsule of each experimental group was obtained,that is,the surface filling ratio of zwitterion.In this paper,using Sprague Dawley(SD)rat as a model,nanocapsules with different zwitterionic surface filling ratios were injected intravenously into rats to study the relationship between the zwitterionic surface content and the blood circulation time of nanocarrier.The results show that when the PC surface filling ratio is controlled within the range of 43-68%,or the CB surface filling ratio is controlled within the range of 20-68%,the nanocapsules have long circulation characteristics,and the half-life can be as high as 37.4 h and 45.3 h,respectively.When the surface filling ratio of zwitterion reaches a certain value(PC:43%;CB:20%),with the further increase of the surface filling ratio,there is no significant change in the blood circulation time of the nanocapsules.The long circulation characteristic comes from that when the zwitterionic surface filling ratio reaches the certain value,the hydration capacity generated by the PC chain or CB chain is sufficient to effectively resist the adsorption of non-specific proteins and inhibit the phagocytosis of macrophages.This study clarified the relationship between the surface content of zwitterions and the blood circulation time of nanocarrier,which provides basis for the the construction of an ideal protein drug delivery system based on extracellular targets.