Control of burst release from nanogels via layer by layer assembly

Undesirable burst release phenomenon is commonly encountered in nanostructured delivery systems, and should be addressed. The present study demonstrates a simple and practical way to reduce or minimize high burst release associated with nanoparticulate delivery systems. Drug loaded nanogels of size less than 200 nm were successfully coated with alternating layers of poly(allylamine hydrochloride) (PAH, cationic) and poly(sodium 4-styrenesulfonate) (PSS, anionic) polyelectrolytes. With every layer of polyelectrolyte, the radius increased by 2 nm, and the zeta-potential alternated between positive and negative values. PSS coated nanogels were stable at all pH, while PAH coated nanogels were only stable up to pH of 8. A drug selective electrode (DSE) was used to directly measure the concentration of procaine hydrochloride (PrHy) from MAA-EA coated nanogels. The high burst release was reduced or minimized when the number of layers of polyelectrolyte was increased. An empirical relationship describing the number of polyelectrolyte layers and time to attain steady-state drug concentration (tau(D)) was developed, where tau(D) increased with increasing polyelectrolyte layers.