Comparison of liposomal and NLC (nanostructured lipid carrier) formulations for improving the transdermal delivery of oxaprozin: Effect of cyclodextrin complexation

- Development and comparison of liposomal and NLC (nanostructured lipid carrier) formulations to improve topical bioavailability of oxaprozin.
- Evaluation of the effectiveness of the combined approach of drug cyclodextrin (CD) complexation and complex entrapment in nanocarriers (NC).
- Permeation studies by artificial membranes: better power of drug-CD-NC systems than drug-NC or drug-CD ones; higher effect of liposomes than NLC.
- Permeation studies by human skin confirmed such results and evidenced an enhancer effect of NC components and/or of randomly-methylated ßCD.

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.

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