SURFACE ENGINEERED NANOSPHERES WITH ENHANCED DRAINAGE INTO LYMPHATICSAND UPTAKE BY MACROPHAGES OF THE REGIONAL LYMPH-NODES

The concept of steric stabilization as used in colloid science is appl ied to carefully manipulate the drainage and lymphatic distribution of subcutaneously administered model polystyrene nanospheres. A wide ran ge 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 co-polymers and nanosphere drainage and passageway across tissue lymph interface in d ermal lymphatic capillaries in the rat footpads; the longer the POE ch ains, the faster the particle drainage. Nanospheres conditioned with b lock co-polymers of POE chains of 5-15 ethylene oxide units are effect ively opsonized in lymphatics; a process which dramatically enhances s equestration (up to 40% of the administered dose) by macrophages of th e regional lymph nodes. If the dimensions of the stabilizing POE chain s of the poloxamines and poloxamers exceed the range of the Van der Wa als force of attraction, opsonization fails to occur and rapidly drain ed engineered vehicles escape clearance by macrophages of the regional nodes, reach the systemic circulation and remain in the blood for pro longed periods. These observations suggest that a lymphatic delivery c omposition based on polymer-coated particles will be advantageous for many applications in clinical and experimental medicine.