Bioadhesive polymer/lipid hybrid nanoparticles as oral delivery system of raloxifene with enhancive intestinal retention and bioavailability.

Raloxifene (RLX) is a second-generation selective estrogen receptor modulator used to treat osteoporosis in postmenopausal women. RLX fails to be developed into injectable dosage forms due to poor solubility. Although oral formulations are clinically available, the lower bioavailability (<2%) embarrasses the pharmaceutists. This work reported a bioadhesive nanosystem intended for oral delivery of RLX to enhance its oral bioavailability and address the formulation challenge. The bioadhesive nanosystem refers to polymer-lipid hybrid nanoparticles made up of Carbopol 940, glyceryl distearate, and TGPS. RLX was solidly encapsulated into bioadhesive nanoparticles (NPs) through a nanoprecipitation technique along with synchronous desalting of RLX·HCl. The resultant RLX-loaded NPs (RLX-NPs) were characterized by particle size, potential, morphology, and entrapment efficiency. The release and oral bioavailability of RLX-NPs in rats were comparatively investigated with RLX-loaded common lipid nanoparticles (RLX-NPs). The preferred formulation possesses a particle size of 150 nm around with a polydispersity index (PDI) of 0.282. RLX-NPs exhibited slower drug release than RLX-NPs owing to the presence of an adhesive layer. After oral administration, RLX-NPs resulted in significant enhancement in the bioavailability of RLX, up to 556.9% relative to RLX suspensions, while it was merely 244.7% for RLX-NPs. Cellular testing and transport imaging demonstrated that NPs were endowed with excellent intestinal epithelial affinity and absorbability. Our study affords an alternative option for designing a suitable oral delivery system specific to amphiphobic drugs like RLX·HCl.