Preparation and characterization of biodegradable nanoparticles containing a lipophilic drug in water-soluble or insoluble form

Numerous studies have shown that cloricromene, a semi-synthetic non-anticoagulant coumarin derivative, exerts a clear protective action in several experimental models of ischaemia and shock (1). The antithrombotic and anti-ischemic effects of cloricromene are evident in the peripheral ischemia for the difficult of the drug to pass the brain-blood barrier (BBB). Recently, polymeric nanoparticles have been proposed as interesting alternative to the traditional approaches to overcome brain drug delivery obstacles (2). Among the techniques proposed in the preparation of nanoparticles from polyester polymers, such as poly (D,L lactide) (PLA) or poly (D,L lactide-co-glicolide) (PLGA), the nanoprecipitation method (3) represents an easy and reproducible technique to obtain nanoparticles below 200 nm. However, this method is basically applicable to lipophilic drugs and several attempts are developed in order to improve hydrophilic drug encapsulation. Cloricromene is rapidly metabolised in vitro or in vivo in the blood into a stable and active catabolite (Cloricromene acid, AD6-acid) through the hydrolysis of an ester bound within the molecule (Fig 1). Cloricromene (as chloride salt, AD6) is freely soluble in water even if it is very lipophilic (log P= 3.96); on the contrary the catabolite is poorly soluble in water and is less lipophilic than Cloricromene (log P = 3.12). The aim of this paper was to evaluate which of the two drug forms has more possibility to be encapsulated efficiently in the nanoparticles, according to the parameters used in the preparation.