Isotretinoin-loaded nanocapsules: stability and cutaneous penetration by tape stripping in human and pig skin.

The cutaneous penetration of isotretinoin-loaded poly(epsilon-caprolactone) nanocapsules (GEL-NCISO) was compared to that of free isotretinoin (GEL-FREE) incorporated in hydrogels by tape stripping in excised human and pig skin. The physicochemical stability of isotretinoin-loaded nanocapsules and a nanoemulsion (used as a control) was evaluated using multiple light scattering, quantifying drug content and determining particle size, polydispersion index, zeta potential and pH for 60 days. A photostability study was also carried out. GEL-FREE and GEL-NCISO were applied to human and pig skin and penetration was assessed by tape stripping in Franz diffusion cells. The isotretinoin-loaded nanocapsules showed suitable physicochemical characteristics for topical administration, physical stability for 2 months at room temperature and under UVA radiation. In vitro tape stripping in human and pig skin showed that no isotretinoin reaches the receptor compartment for both formulations up to 8 h. Nanoencapsulation increased isotretinoin skin penetration for both skin stratum corneum. Pig skin was more permeable than human since higher isotretinoin concentrations were found at human upper skin layers for both formulations. Similar proportion of cutaneous penetration for human and pig skin were observed although different amounts of drug were detected in the stratum corneum of both skin specimens in vitro. A positive Pearson product moment correlation coefficient (0.79) between human and pig skin penetration in vitro was obtained, thus, pig skin can be considered suitable for predicting cutaneous penetration of isotretinoin in humans in vitro.

Evaluation of gatifloxacin penetration into skeletal muscle and lung by microdialysis in rats.

This study aimed to investigate gatifloxacin distribution into skeletal muscle and lung interstitial fluid by microdialysis and to correlate free tissue and free plasma levels of the drug. Microdialysis recoveries were determined in vitro by extraction efficiency and retrodialysis at 80, 160 and 400 ng/ml resulting in 33.5+/-1.3%, 33.1+/-1.2%, 31.8+/-2.7% and 31.4+/-2.6%, 33.1+/-2.2%, 30.6+/-3.3%, respectively. In vivo recovery by retrodialysis in Wistar rats' skeletal muscle and lung were 29.1+/-1.0% and 30.7+/-1.4%, respectively. The recovery was constant and independent on the method or media used. Gatifloxacin tissue penetration was investigated after intravenous dosing of 6 mg/kg to Wistar rats. Free skeletal muscle, lung and plasma profiles were virtually superimposable resulting in similar area under the curve (AUC(0-9)) of 3888+/-734 ng h/ml, 4138+/-1071 ng h/ml and 3805+/-577 ng h/ml, respectively (alpha=0.05). The tissue distribution factors were 1.02 and 1.08 for muscle and lung relative to plasma. In conclusion, free plasma levels are a good surrogate for gatifloxacin active levels at the infection site.