Evaluation of in-vivo topical anti-inflammatory activity of indometacin from liposomal vesicles.
The aim of this study was to evaluate the in-vivo drug release profile of indometacin-loaded liposomes into the skin. Large unilamellar vesicles (LUVs), composed of dipalmitoyl-L-alpha-phosphatidylcholine and cholesterol (9:1), were obtained using the extrusion method and then incorporated in hydrogels (LUV-A and LUV-B). The delivery of indometacin from the liposomal system was evaluated by determining its in-vivo local anti-inflammatory activity after cutaneous application of liposomal gel formulations; the anti-inflammatory activity is directly proportional to the amount of drug that actually crosses the skin. UVB-induced erythema on healthy human volunteers was chosen as the inflammatory model and the extent of erythema was monitored by the non-invasive technique of reflectance spectrophotometry. The results showed that LUV dispersions containing indometacin provided a high percentage of entrapped drug (approximately 84%). Furthermore, in-vivo findings revealed that the anti-inflammatory effect was more prolonged when indometacin was delivered from a liposomal gel formulation rather than from a gel formulation without liposomes. In particular, the indometacin-loaded gel formulation LUV-A showed a sustained effect, probably related to an interaction between LUV lipids and stratum corneum lipid structure. This interaction produces a depot in the stratum corneum that ensures sustained release of the drug to deeper skin layers.
Puglia
Carmelo
C
Department of Pharmaceutical Sciences, School of Pharmacy, University of Catania, Catania, Italy. capuglia@unict.it
Trombetta
Domenico
D
Venuti
Vincenza
V
Saija
Antonella
A
Bonina
Francesco
F
D015060:1,2-Dipalmitoylphosphatidylcholine; D000287:Administration, Topical; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002784:Cholesterol; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004890:Erythema / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D005260:Female; D006801:Humans; D020100:Hydrogels; D007213:Indomethacin / Q000008:administration & dosage*; D008081:Liposomes / Q000737:chemistry; D008297:Male; D010539:Permeability; D012869:Skin Absorption; D014466:Ultraviolet Rays
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020100:Hydrogels; D008081:Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine; D002784:Cholesterol; D007213:Indomethacin