Development of nanoparticles-in-microparticles system for improved local retention after intra-articular injection.

To increase the intra-articular (IA) retention time of osteoarthritis drugs in the synovial cavity and slow down the burst release of microspheres (MPs), we prepared a novel drug delivery system named nanoparticles-in-microspheres (NiMs). The system was constructed by dispersing the brucine-loaded nanoparticle, which was prepared by an emulsification method in the MPs. The NiMs were characterized by scanning electron microscope, Fourier transform infrared spectra and differential scanning calorimetry. After investigating the biocompatibility with synovium of NiMs in rats, the pharmacokinetics was studied and FX-imaging was used to visualize the transmission of nanoparticles after IA administration in rats. From the results, we know that the NiMs were spherical, there was no chemical bond between the drug and the polymer, and the drug was dispersed in the polymer in an amorphous form. Compared with MPs (41%), the burst release of NiMs could be slowed down to 9%. After that, the drug was released from NiMs by diffusion. The results of FX imaging in rats showed that the NiMs could stay in the articular cavity for over 11 d. The studies of pharmacokinetics revealed that the NiMs could slow down the burst release and improve retention in vivo. This study demonstrates the feasibility of using NiMs to slow down the burst release and increase the retention of therapeutic agents in articular joints.