The permeability of the Biopharmaceutics Classification System (BCS) class III drugs are low, and their oral bioavailability needs to be improved. In this study, we attempted to design oral formulations containing famotidine (FAM) nanoparticles to overcome the limitations of BCS class III drugs. Dispersions containing FAM nanoparticles with a particle size of approximately 50–220 nm were produced by the bead-milling treatment. Moreover, we succeeded in preparing an orally disintegrating tablet containing FAM nanoparticles using the dispersions described above, additives (D-mannitol, polyvinylpyrrolidone, and gum arabic), and freeze-dry treatment (FAM-NP tablet). The FAM-NP tablet was disaggregated 3.5 s after addition to purified water, and the FAM particles in the redispersion of the FAM-NP tablet stored for 3 months were nano-sized (141 ± 6.6 nm). The ex-vivo intestinal penetration and in vivo absorption of FAM in rats applied with the FAM-NP tablet were significantly higher than those in rats applied with the FAM tablet containing microparticles. In addition, enhanced intestinal penetration of the FAM-NP tablet was attenuated by an inhibitor of clathrin-mediated endocytosis. In conclusion, the orally disintegrating tablet containing FAM nanoparticles improved low mucosal permeability and low oral bioavailability and overcame these issues of BCS class III drugs as oral formulations.

It has recently been reported that lanosterol (LAN) plays a preventive role against lens opacification through the reversal of crystalline aggregation. However, the effect of LAN is not sufficient to restore lens transparency. In this study, we designed ophthalmic nanosuspensions (LAN-ONSs and NIL-ONSs) based on LAN and nilvadipine (NIL), which can counteract cataract-related factors (e.g., enhanced Ca2+ and calpain levels), and investigated whether the combination of LAN-ONSs and NIL-ONSs can restore the nuclear lens opacity in sodium-selenite-induced cataractic rats (cataractic rats). The mean particle sizes of the LAN-ONSs and NIL-ONSs were 108.8 nm and 89.0 nm, respectively. The instillation of the LAN-ONSs or NIL-ONSs successfully delivered the drugs (LAN or NIL) into the lenses of the rats, although the instillation of LAN-ONSs or NIL-ONSs alone did not increase lens transparency in the cataractic rats. On the other hand, the cataract-related factors (enhanced Ca2+ and calpain levels) were significantly alleviated by the combination of LAN-ONSs and NIL-ONSs; furthermore, the perinuclear refractile ring in the lens nucleus and enhanced number of swollen fibers were attenuated by the LAN-ONS and NIL-ONS combination. Moreover, the opacity levels in the cataractic rats were reduced after treatment with the combination of LAN-ONSs and NIL-ONSs. It is possible that the combination of LAN and NIL will be useful for the treatment of lens opacification in the future.

Background It is important to design an effective formulation to enhance the skin penetration, and nanotechnologies have been used in dermal and transdermal drug delivery. In this study, we prepared formulations (gels) containing l-menthol and felbinac (FEL) solid nanoparticles (FEL-NP gel) for topical application, and investigated the local and systemic absorption of the prepared FEL-NP gel. Methods FEL solid nanoparticles were obtained by bead milling of FEL powder (microparticles), and a topical formulation (FEL-NP gel) consisting of 1.5% FEL solid nanoparticles), 2% carboxypolymethylene, 2% l-menthol, 0.5% methylcellulose, and 5% 2-hydroxypropyl-β-cyclodextrin (w/w %) were prepared. Results The particle size of FEL nanoparticles was 20–200 nm. The released FEL concentration from FEL-NP gel was significantly higher than that from FEL gel without bead mill treatment (carboxypolymethylene gel in which FEL microparticles (MPs) instead of FEL nanoparticles were incorporated, FEL-MP gel), and FEL was released as nanoparticles from the gel. Moreover, both transdermal penetration and percutaneous absorption of FEL-NP gel were significantly increased compared with those of FEL-MP gel, and the area under the FEL concentration-time curve (AUC) of FEL-NP gels was 1.52- and 1.38-fold of commercially available FEL ointment and FEL-MP gel, respectively. In addition, after 24 h of treatment, the FEL content in rat skin treated with FEL-NP gels was 1.38- and 2.54-fold higher than that when treated with commercially available FEL ointment and FEL-MP gel, respectively. Moreover, the enhanced skin penetration of FEL-NP gels was significantly attenuated by inhibition of energy-dependent endocytosis, such as clathrin-mediated endocytosis. Conclusions We successfully prepared a topically applied carboxypolymethylene gel containing FEL nanoparticles. In addition, we observed that the endocytosis pathway was mainly related to the high skin penetration of FEL nanoparticles, and FEL-NP gel application resulted in high local tissue concentration and systemic absorption of FEL. These findings provide useful information for the design of topically applied nanoformulations against inflammation by providing local and systemic effects.

We previously designed the formulation containing minoxidil (MXD) nanoparticles (MXD-NPs), and found that the MXD-NPs can mainly deliver MXD into hair bulbs via hair follicles pathway, and that the therapeutic e‹ciency for hair growth is higher in comparison with the formulation containing dissolved MXD. In this study, we investigated whether the skin environmental changes by the treatment of steam towel, ethanol, l-menthol and commercially available (CA) carpronium aŠect the drug behavior in the MXD-NPs-applied mice. The steam towel, ethanol, l-menthol and CAcarpronium were pre-treated 3 min before MXD-NPs application, and the MXD content in the hair bulge, bulb, skin tissue and blood of mice were measured 4 h after MXD-NPs application. No signiˆcant diŠerence of MXD levels in the blood was observed by the pre-treatment of steam towel, ethanol, l-menthol and CA-carpronium. On the other hand, the pre-treatment of steam towel and l-menthol enhanced the MXD levels in hair bulge and/or bulb. Although, the MXD levels in hair bulge and bulb were not changed by the pre-treatment of ethanol, the MXD levels in skin tissue was higher than that of saline-pre-treated group (control). The MXD levels in hair bulge, bulb and skin tissue of mice pretreated with CA-carpronium were remarkably higher in comparison with control. In conclusion, we showed that the changes in skin environment by the steam towel, ethanol, l-menthol and CA-carpronium aŠected the absorption of MXD-NPs, and these increased MXD levels in the hair bulb and blood by the combination may enhance the therapeutic e‹ciency without side eŠects.