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Size,shape,charge and“stealthy”surface:Carrier properties affect the drug Circulation time in vivo

Asian Journal of Pharmaceutical Sciences 2021年第4期16卷 444-458页

作者： Jinwei Di Xiang Gao Yimeng Du Hui Zhang Jing Gao Aiping Zheng State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing 100850China

The present review sets out to discuss recent developments of the effects and mechanisms of carrier properties on their Circulation time.For most drugs,sufficient in vivo Circulation time is the basis of high bioavailability.Drug carrier plays an irreplaceable role in helping drug avoid being quickly recognized and cleared by mononuclear phagocyte system,to give drug enough time to arrive at targeted organ and tissue to play its therapeutic effect.The physical and chemical properties of drug carriers,such as size,shape,surface charge and surface modification,would affect their in vivo Circulation time,metabolic behavior and biodistribution.The final Circulation time of carriers is determined by the balance between macrophage recognitions,blood vessel penetration and urine excretion.Therefore,when designing the drug delivery system,we should pay much attention to the properties of drug carriers to get enough in vivo Circulation time to arrive at target site eventually.This article mainly reviews the effect of carrier size,size,surface charge and surface properties on its Circulation time in vivo,and discusses the mechanism of these properties affecting Circulation time.This review has reference significance for the research of long-circulation drug delivery system.

关键词： Drug carrier Circulation time Physical and chemical properties Macrophages Phagocytosis

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A lipophilic prodrug of Danshensu:preparation,characterization,and in vitro and in vivo evaluation

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Chinese Journal of Natural Medicines 2017年第5期15卷 355-362页

作者： GUO Xue-Jiao FAN Xue-Jiao QIAO Bin GE Zhi-Qiang Department of Pharmaceutical Engineering School of Chemical Engineering and Technology Tianjin University Education Ministry Key Laboratory of Systems Bioengineering Tianjin 300072 China

Danshensu [3-(3, 4-dihydroxyphenyl) lactic acid, DSS], one of the significant cardioprotective components, is extracted from the root of Salvia miltiorrhiza. In the present study, an ester prodrug of Danshensu(DSS), palmitoyl Danshensu(PDSS), was synthesized with the aim to improve its oral bioavailability and prolong its half-life. The in vitro experiments were carried out to evaluate the physicochemical properties and stability of PDSS. Although the solubility of PDSS in water was only 0.055 mg·mL^(-1), its solubility in Fa SSIF and Fe SSIF reached 4.68 and 9.08 mg·mL^(-1), respectively. Octanol-water partition coefficient(log P) was increased from-2.48 of DSS to 1.90 of PDSS. PDSS was relatively stable in the aqueous solution in pH range from 5.6 to 7.4. Furthermore, the pharmacokinetics in rats was evaluated after oral administration of PDSS and DSS. AUC and t1/2 of PDSS were enhanced up to 9.8-fold and 2.2-fold, respectively, compared to that of DSS. Cmax was 1.67 ± 0.11 μg·mL^(-1) for PDSS and 0.81 ± 0.06 μg·m L-1 for DSS. Thus, these results demonstrated that PDSS had much higher oral bioavailability and longer Circulation time than its parent drug.

关键词： Danshensu Prodrug Oral bioavailability Circulation time

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Application of sialic acid/polysialic acid in the drug delivery systems

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Asian Journal of Pharmaceutical Sciences 2014年第2期9卷 75-81页

作者： Ting Zhang Zhennan She Zhenjun Huang Jing Li Xiang Luo Yihui Deng School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China

The properties of modified biomaterial are gaining more and more importance in drug delivery systems.Sialic acid(SA)and polysialic acid(PSA)serve as endogenous substances,which are non-immunogenic and biodegradable.At the same time,SA modification of the drugs/carriers can enhance the uptake of tumor cell and retention in brain;PSA modifi-cation can reduce the immunogenicity of the proteins or polypeptides and increase Circulation time of the modified drugs/carriers in the blood,thus achieving active targeting effect.These properties offer a variety of opportunities for applications in drug delivery systems.This article summarizes the biological functions of SA and PSA and presents the technologies of SA/PSA modified small molecule drugs,proteins and carriers in drug delivery systems.

关键词： Sialic acid Polysialic acid Drug delivery system Active targeting Circulation time

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