Cinacalcet HCl Loaded PLGA Nanoparticles Using the Porous Carrier

Background: Cinacalcet HCl, a calcimimetic, BCS class IV drug with low oral bioavailability. Polymeric nanoparticles are widely used as biomaterials owing to their biocompatibility, biodegradability, varied structures, low toxicity, simple and easy formulation process. Objective: To enhance the oral bioavailability of poorly water soluble drug i.e., Cinacalcet HCl by using a suitable particulate nanocarrier system i.e., Polymeric Nanoparticles. Methods: A Biodegradable Cinacalcet HCl (CH) loaded Poly (Lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by nano precipitation method using Poloxamer-188 as stabilizer. The experimental parameters like polymer concentration, stabilizer concentration, temperature and RPM speed were optimized. An optimized Polymeric nanoparticles (PNP F8) was solidified by adsorption to porous carrier sylysia 350. Results: PNP F8 exhibited particle size 155 nm with low PDI (0.231) and high zeta potential (-21.3 mV). In vitro diffusion study revealed sustain release of CH for 24 h for both PNP (F8) and solidified PNP (F8). Pharmacokinetics after oral administration of PNP (F8) and solidified PNP (F8) exhibited 5 fold increases in bioavailability. Thus, both PNP (F8) and solidified PNP (F8) showed significant improvement in oral bioavailability. Conclusion: Adsorption to polymeric nanoparticles to porous carriers like sylysia 350 can be considered as a promising approach for its long term stability.