Development of doxycycline and atorvastatin-loaded chitosan nanoparticles for local delivery in periodontal disease

The effectiveness of the local treatment depends on the ability of the release system to deliver drugs efficiently as well as control of both infection and inflammation component of the disease. The present study aimed to develop an atorvastatin (AS) and doxycycline (DS) dual drug loaded chitosan nanoparticle (CSNP) delivery system for the local treatment of periodontal disease. For this purpose, AS and DS loaded CSNPs at different drug weights were prepared by nanoprecipitation technique to improve the oral bioavailability of the drug. Particle size, encapsulation efficiency (EE), drug loading (DL), zeta potential and in vitro drug release properties were determined in artificial saliva at 37 °C. The AS/DS drug-loaded CSNPs exhibited good encapsulation efficiency from 81.6 ± 1.8% to 90.4 ± 2.4%. Particle size of prepared AS, DS or AS/DS loaded CSNPs was ranged from 60.66 ± 4.97 nm to 87.44 ± 6.41 nm with a low polydispersity index (PI) value. AS drug loaded nanocarriers showed a slow and sustained release of approximately 85% in a span of 4 or 6 h and decreased to 50% at 216 h (9 days), while DS drug loaded nanocarriers exhibited sustained release of maximum 35% in 24 h and decreased to 1% at 120 h (5 days). In vitro antimicrobial study showed that AS/DS loaded chitosan nanoparticles were more effective against Staphylococcus aureus than Escherichia coli. Cytotoxicity experiments showed that AS/DS loaded CSNP systems had no cytotoxic effects. In conclusion, a dual drug loaded CSNP was successfully developed which might be a promising formulation for the local drug delivery of DS and AS into the periodontal pocket as adjunctive therapy.

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