Poly(rac-lactide) nanocapsules containing diclofenac: protection against muscular damage in rats

The aim of this work was to determine whether encapsulation of a non steroi dal anti inflammatory agent within nanocapsules could reduce local toxicity after intramuscular injection. Diclofenac-loaded nanocapsules were prepare d by deposition of poly(rac-lactic acid) polymer, and administered intramus cularly to male Wistar rats. Plasma creatine phosphokinase (CPK) activity a nd histological examination were used to assess local tissue damage. Follow ing a single intramuscular injection of diclofenac (0.8 mg), CPK activity w as shown to depend on both the type of dosage form and, in the case of nano capsules, on the chemical nature of the central oily con. Lower CPK activit y was observed with nanocapsules prepared from Miglyol 810(R), a caprylic/c apric triglyceride, while nanocapsules prepared from benzyl benzoate, eithe r empty or containing diclofenac, exhibited the same CPK activity as the dr ug solution. Histopathological examination performed three days after admin istration of free diclofenac or nanocapsules containing diclofenac prepared from Miglyol 810(R) revealed that a much more intense inflammation was obt ained with the solution than with nanocapsules. In conclusion, when appropr iately formulated, nanocapsules can considerably reduce the muscular damage caused by diclofenac.