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 steroidal antiinflammatory agent within nanocapsules could reduce local toxicity after intramuscular injection. Diclofenac-loaded nanocapsules were prepared by deposition of poly(rac-lactic acid) polymer, and administered intramuscularly to male Wistar rats. Plasma creatine phosphokinase (CPK) activity and histological examination were used to assess local tissue damage. Following a single intramuscular injection of diclofenac (0.8 mg), CPK activity was shown to depend on both the type of dosage form and, in the case of nanocapsules, on the chemical nature of the central oily core. Lower CPK activity was observed with nanocapsules prepared from Miglyol 810, a caprylic/capric triglyceride, while nanocapsules prepared from benzyl benzoate, either empty or containing diclofenac, exhibited the same CPK activity as the drug solution. Histopathological examination performed three days after administration of free diclofenac or nanocapsules containing diclofenac prepared from Miglyol 810 revealed that a much more intense inflammation was obtained with the solution than with nanocapsules. In conclusion, when appropriately formulated, nanocapsules can considerably reduce the muscular damage caused by diclofenac.
Guterres
S S
SS
Laboratoire de Pharmacie Galénique et Biopharmacie, UMR CNRS 8612, Faculté de Pharmacie, Université Paris-Xl, Châtenay-Malabry, France.
Fessi
H
H
Barratt
G
G
Puisieux
F
F
Devissaguet
J P
JP
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects*; D019540:Area Under Curve; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects; D002214:Capsules / Q000008:administration & dosage / Q000737:chemistry*; D003238:Connective Tissue / Q000187:drug effects / Q000473:pathology; D003402:Creatine Kinase / Q000097:blood / Q000187:drug effects; D004008:Diclofenac / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D011091:Polyesters / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000008:administration & dosage / Q000009:adverse effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001565:Benzoates; D002214:Capsules; D011091:Polyesters; D014280:Triglycerides; C433530:miglyol 810; D004008:Diclofenac; C033616:poly(lactide); D003402:Creatine Kinase; C006723:benzyl benzoate