Methods are disclosed for preparing novel biodegradable cross-linked nanoparticles based on covalently cross-linking modifications of hyaluronic acid. The final products of the present invention are stable in aqueous media, and may be used as detergents and as additives for pharmaceutical compositions for drug delivery, DNA carrier system and other applications. The nanoparticles made from the biopolymers of the present invention may also be used in controlled release applications, super-absorbent materials as well as biomaterials like enzyme immobilization.