Surface engineered nanospheres with enhanced drainage into lymphatics and uptake by macrophages of the regional lymph nodes

FEBS Letters

Christy, N.M.¹  Hawley, A.E.¹  Davis, S.S.¹  Illum, L.¹  Moghimi, S.M.¹  Gray, T.² 

[1] Departments of Pharmaceutical Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, UK;Departments of Histopathology, University of Nottingham, University Park, Nottingham, NG7 2RD, UK

关键词: Lymphatic system;    Lymph node;    Nanosphere;    Macrophage;    Poloxamine;    Poloxamer;    Drug carrier;   

DOI  :  10.1016/0014-5793(94)00351-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The concept of steric stabilization as used in colloid science is applied to carefully manipulate the drainage and lymphatic distribution of subcutaneously administered model polystyrene nanospheres. A wide range of synthetic polyoxyethylene (POE)/polyoxypropylene (POP) block co-polymers of poloxamine and poloxamer series have been used to produce sterically stabilized nanospheres. We have found a correlation between the length of the stabilizing POE chains of the block copolymers and nanosphere drainage and passageway across tissue lymph interface in dermal lymphatic capillaries in the rat footpads; the longer the POE chains, the faster the particle drainage. Nanospheres conditioned with block co-polymers of POE chains of 5–15 ethylene oxide units are effectively opsonized in lymphatics; a process which dramatically enhances sequestration (up to 40% of the administered dose) by macrophages of the regional lymph nodes. If the dimensions of the stabilizing POE chains of the poloxamines and poloxamers exceed the range of the Van der Waals force of attraction, opsonization fails to occur and rapidly drained engineered vehicles escape clearance by macrophages of the regional nodes, reach the systemic circulation and remain in the blood for prolonged periods. These observations suggest that a lymphatic delivery composition based on polymer-coated particles will be advantageous for many applications in clinical and experimental medicine.

【 授权许可】

Unknown