RESUMO
In this study, flurbiprofen (FB) loaded poly(d,l-lactide-co-glycolide) (PLGA) and PLGA with poly(ethylene glycol) (PLGA-PEG) nanospheres (NSs) with and without hydroxypropyl-ß-cyclodextrin (HPßCD) were developed as skin controlled delivery systems. X-ray diffraction was used to determine the physical state of the entrapped drug. Results showed that the drug in PLGA NSs was present in the form of a molecular dispersion (dissolved state) in the polymers, whereas in PLGA-PEG NSs, the drug was present in both molecular dispersion and crystalline forms. Furthermore, HPßCD provided solubilization of the free FB present on the surface of the PLGA-PEG NSs and a complete amorphosization of the drug was obtained. Optical analyses using TurbiscanLab(®) demonstrated that HPßCD provided an efficient steric stability of the NSs, preventing particle aggregation. The ex vivo permeation profiles of the NSs and conventional FB solution were evaluated using human skin. Results demonstrated that only PLGA-PEG NSs showed slight permeation improvement. However, after 24h, the FB retained in the skin was about 9-fold higher with NSs compared with the control solution, attributed to the reservoir effect of NSs acting as a depot, sustaining the drug and limiting its systemic absorption. In vivo performance of NSs was evaluated by assessing anti-inflammatory efficacy in TPA-induced mouse ear edema. Topically applied NSs significantly decreased in vivo inflammation compared to the control solution and the anti-inflammatory efficacy of HPßCD NSs was stronger than NSs without HPßCD. In vivo skin irritation evaluated by the in vivo Draize test showed no irritation of the formulations tested.