Self-assembled drug delivery systems. 1. Properties and in vitro/in vivo behavior of acyclovir self-assembled nanoparticles (SAN).

摘要: Abstract Self-assembled drug delivery systems (SADDS) were designed in the paper. They can be prepared from amphiphilic conjugates of hydrophilic drugs and lipids through self-assembling into small-scale aggregates aqueous media. The outstanding characteristic SADDS is that they are nearly wholly composed prodrugs. self-assembled nanoparticles (SAN) as one had been lipid derivative acyclovir (SGSA) previous further studied on properties vitro/in vivo behavior this SAN kept physical state stable upon centrifugation or some additives including inorganic salts, alkaline solutions, surfactants liposomes except for HCl solution, CaCl 2 solution animal plasma. Autoclave bath heat sterilization hardly influenced SAN. However, gamma-irradiation strongly destroyed structure SGSA was degraded. showed good stability weak acidic neutral buffers although it very sensitive to solutions carboxylester enzymes, half-lives ( t 1/2 ) which buffer at pH 7.4, 12.0, pig liver enzyme rabbit plasma, tissue homogenate 495, 21, 4.7, 25 8.7 h, respectively. Compared with a disordered state, specific bilayer structures could protect hydrolysis hiding ester bonds. hemolytic action because insert erythrocyte membranes. Both high concentration samples long incubation time improved hemolysis. No hemolysis observed if additional volume less than 10% whole blood spite SGSA. Plasma proteins interfere interaction between erythrocytes by binding vitro antiviral activity limited possibly Vero cells, little cell toxicity possible due amphiphilicity A macrophage line QXMSC1 cells uptake but not significantly. rapidly removed circulation after bolus iv administration rabbits short distribution (1.5 min) elimination (47 min). mainly distributed liver, spleen lung administration, eliminated slowly these tissues , about 7 h). It would appear nanosized trapped mononuclear phagocyte system. combine prodrugs, molecular self-assembly nanotechnology, hopefully become novel approaches.