Comparison of liposomal and NLC (nanostructured lipid carrier) formulations for improving the transdermal delivery of oxaprozin: Effect of cyclodextrin complexation.
The combined strategy of drug-cyclodextrin (CD) complexation and complex loading into nanocarriers (deformable liposomes or nanostructured lipid carriers (NLC)), was exploited to develop effective topical formulations for oxaprozin transdermal administration. Oxaprozin was loaded as ternary complex with randomly-methylated-ßCD and arginine, selected as the best system in improving drug solubility. The colloidal dispersions, characterized for particle size, zeta-potential and entrapment efficiency, were investigated for drug permeation properties in comparison with a plain drug aqueous suspension, a ternary complex aqueous solution and a plain drug liposomal or NLC dispersion. Experiments with artificial membranes showed that the joined use of CD and both liposomes or NLC enabled a marked increase of the drug permeability (16 and 8 times, respectively) and was significantly more effective (P<0.05) than the drug as ternary complex (3.2 times increase), and the corresponding liposomal or NLC dispersion of plain drug (5.6 and 4.3 times increase, respectively). Experiments with excised human skin confirmed the significantly (P<0.05) better performance of deformable liposomes than NLC in promoting drug permeation; moreover, they evidenced a more marked permeability increase compared to the plain drug (24 and 12 fold, respectively), attributed to a possible enhancer effect of the nanocarriers components and/or of the randomly-methylated-ßCD.
Department of Chemistry, School of Human Health Sciences, University of Florence, Via Schiff 6, Sesto Fiorentino I-50019, Florence, Italy.
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Mennini
Department of Chemistry, School of Human Health Sciences, University of Florence, Via Schiff 6, Sesto Fiorentino I-50019, Florence, Italy.
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Cirri
Department of Chemistry, School of Human Health Sciences, University of Florence, Via Schiff 6, Sesto Fiorentino I-50019, Florence, Italy.
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Maestrelli
Department of Chemistry, School of Human Health Sciences, University of Florence, Via Schiff 6, Sesto Fiorentino I-50019, Florence, Italy. Electronic address: paola.mura@unifi.it.
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Mura
D000279:Administration, Cutaneous; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003505:Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D049329:Nanostructures; D000077431:Oxaprozin; D010316:Particle Size; D010539:Permeability / Q000187:drug effects; D011422:Propionates / Q000008:administration & dosage / Q000737:chemistry*; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects; D012995:Solubility; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry
D003505:Cyclodextrins; D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D011422:Propionates; D047392:beta-Cyclodextrins; D000077431:Oxaprozin
Arginine; Caprylocaproyl macrogol-8 glycerides (Labrasol(®)); Carbopol 940 (PubChem CID 6581, Acrylic Acid); Deformable liposomes; Excised human skin; Glycerol distearate (Precirol(®) ATO 5); In vitro skin permeation; Nanostructured lipid carriers (NLC); Oxaprozin; Oxaprozin (PubChem CID 4614); Polyoxyethylene sorbitan monoleate (PubChem CID 86289060); Randomly methylated ß-cyclodextrin; Randomly-methylated-ß-cyclodextrin (PubChem CID 122143); Sodium cholate (PubChem CID 23668194); Stearylamine (PubChem CID 15793); l-Arginine (PubChem CID 6322)