Physico-chemical characterization and in vivo evaluation of indomethacin ethyl ester-loaded nanocapsules by PCS, TEM, SAXS, interfacial alkaline hydrolysis and antiedematogenic activity.
Nanocapsules are vesicular drug carriers constituted of an oil core, a polymeric wall, and surfactants. A general understanding about the influence of the polymeric wall of nanocapsules on the release profiles of drugs is not known. So, this work was devoted to characterize formulations prepared without polymer or containing it at different concentrations. The indomethacin ethyl ester was used as model and the strategy was based on its interfacial alkaline hydrolysis simulating a sink condition for the release. The antiedematogenic activity in rats for ester-loaded-nanocarriers was also evaluated. The nanocapsules (NC) and nanoemulsion (NE) presented particle sizes below 300 nm, polydispersity lower than 1.2 and pH around 5. SAXS analyses showed that the sorbitan monostearate is dissolved in the oil and the polymer presents regions of crystallinity independently on the PCL concentration. TEM analyses showed droplets (NE) and spherical particles (NC). The time for the total disappearance of the ester varied from 12 h to 24 h depending on the polymer concentration. The biexponential model showed that the indomethacin ester was essentially entrapped within the nanocarriers in an extension of 85 to 95%. The half-lives varied from 147 to 289 min for the sustained phases and from 3 to 6 min for the burst phases. The ester-loaded-NC showed significant antiedematogenic activity, while the ester-loaded-NE did not inhibit the carrageenin-induced paw edema. The nanocapsules promoted the absorption of the indomethacin ethyl ester and the presence of the polymer is important to achieve the pharmacological effect.
Cruz
Letícia
L
Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Schaffazick
Scheila R
SR
Dalla Costa
Teresa
T
Soares
Leonardo U
LU
Mezzalira
Graziela
G
da Silveira
Nádya P
NP
Schapoval
Elfrides E S
EE
Pohlmann
Adriana R
AR
Guterres
Sílvia S
SS
D000468:Alkalies / Q000737:chemistry; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry; D002214:Capsules / Q000737:chemistry*; D004487:Edema / Q000188:drug therapy* / Q000473:pathology; D006868:Hydrolysis; D007213:Indomethacin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D008968:Molecular Conformation; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D014961:X-Ray Diffraction
D000468:Alkalies; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; C507313:indomethacin ethyl ester; D007213:Indomethacin