Shielding Therapeutic Drug Carriers from the Mononuclear Phagocyte System: A Review

被引:18
作者
Sathyamoorthy, Nandhakumar [1 ]
Dhanaraju, Magharla Dasaratha [1 ]
机构
[1] GIET Sch Pharm, NH 5 Chaitanya Nagar, Rajahmundry, Andhra Pradesh, India
来源
CRITICAL REVIEWS IN THERAPEUTIC DRUG CARRIER SYSTEMS | 2016年 / 33卷 / 06期
关键词
mononuclear phagocyte system; phagocytosis; opsonization; particulate carriers; PEGylation; steric stabilization; PEGYLATED LIPOSOMAL DOXORUBICIN; ACCELERATED BLOOD CLEARANCE; IN-VIVO BIODISTRIBUTION; STERICALLY STABILIZED LIPOSOMES; ALBUMIN-BOUND PACLITAXEL; PLASMA-PROTEIN ADSORPTION; LOADED POLYMERIC NANOPARTICLES; RECEPTOR-MEDIATED PHAGOCYTOSIS; SINUSOIDAL ENDOTHELIAL-CELLS; MOUSE PERITONEAL-MACROPHAGES;
D O I
10.1615/CritRevTherDrugCarrierSyst.2016012303
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The mononuclear phagocyte system (MPS) defends the body against the invasion of microorganisms by phagocytosis. In the presence of opsonins, the invading matter is readily recognized by phagocytes because of the interaction between receptors on the phagocytic cell surfaces and the modified conformation of opsonins. The particulate carriers, which are otherwise capable of optimizing drug delivery, are subjected to opsonization and phagocytosis by the MPS immediately following intravenous administration. These drug carriers should remain in the bloodstream in order to spatially locate the drug to the target site and temporally control the drug's release from there on; however, they are devastated by opsonization by serum proteins. Therefore, to restrict opsonization, which is critical for recognition of particulate carriers by the MPS, stealth devices have been developed by engineering the carriers' surface characteristics. Physicochemical properties that influence protein immunogenicity include particle size, surface charge, and surface hydrophobicity. Steric stabilization using polyethylene glycol (PEG) and polyethylene oxide (PEO) chains attached to the particle surface is principally effective in preventing the adsorption of serum opsonins. This article reviews the literature on the MPS and its development and functions, as well as approaches for designing long-circulating carrier particles. It also comprehensively reviews parameters affecting the steric characteristics of drug carriers, such as particle size, shape, surface charge, and surface affinity, including PEGylation of carriers.
引用
收藏
页码:489 / 567
页数:79
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