Fluvastatin-Loaded Emulsomes Exhibit Improved Cytotoxic and Apoptosis in Prostate Cancer Cells.

Fluvastatin (FLV) is known to inhibit the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), which is over-expressed in various cancers. FLV has been reported to decrease cancer development and metastasis. However, because of low bioavailability, extensive first-pass metabolism and short half-life of FLV (1.2 h), it is not appropriate for clinical application. Therefore, FLV-loaded emulsomes were formulated and optimized using Box-Behnken experimental design to achieve higher efficiency of formulation. Antitumor activity of optimized FLV-loaded emulsomes was evaluated in prostate cancer cells using cell cytotoxicity, apoptotic activity, cell cycle analysis, and enzyme-linked immunosorbent assay. The FLV-loaded emulsomes exhibited a monodispersed size distribution with a mean particle size less than 100 nm as measured by zetasizer. The entrapment efficiency was found to be 93.74% with controlled drug release profile. FLV-EMLs showed a significant inhibitory effect on the viability of PC3 cells when compared to the free FLV (P < 0.0025). Furthermore, FLV-EMLs showed significant arrest in G2/M and increase in percentage of apoptotic cells as compared to free FLV. FLV-EMLs were more effective than free FLV in reducing mitochondrial membrane potential and increase in caspase-3 activity. These results suggesting that FLV-EMLs caused cell cycle arrest which clarifies its significant antiproliferative effect compared to the free drug. Therefore, optimized FLV-EMLs may be an effective carrier for FLV in prostate cancer treatment.

Development and Evaluation of Polymeric Nanosponge Hydrogel for Terbinafine Hydrochloride: Statistical Optimization, In Vitro and In Vivo Studies.

Terbinafine hydrochloride, although one of the prominent antifungal agents, suffers from low drug permeation owing to its hydrophobic nature. The approach of nanosponge formulation may thus help to resolve this concern. Thus, the present research was envisioned to fabricate the nanosponge hydrogel of terbinafine hydrochloride for topical delivery since nanosponge augments the skin retentivity of the drug. The optimized formulation was obtained using Box Behnken Design. The dependent and independent process parameters were also determined wherein polyvinyl alcohol (%), ethylcellulose (%), and tween 80 (%) were taken as independent process parameters and particle size, polydispersity index (PDI), and entrapment efficiency (EE) were the dependent parameters. The nanosponge was then incorporated into the hydrogel and characterized. In-vitro drug release from the hydrogel was 90.20 ± 0.1% which was higher than the drug suspension and marketed formulation. In vitro permeation potential of the developed formulation through rat skin showed a flux of 0.594 ± 0.22 µg/cm2/h while the permeability coefficient was 0.059 ± 0.022 cm/s. Nanosponge hydrogel was evaluated for non-irritancy and antifungal activity against C. albicans and T. rubrum confirming the substantial outcome. Tape stripping studies exhibited ten times stripping off the skin quantified 85.6 ± 0.21 µg/cm2. The confocal analysis justified the permeation potential of the prepared hydrogel. The mean erythemal score was 0.0, confirming that the prepared hydrogel did not cause erythema or oedema. Therefore, based on results obtained, nanosponge hydrogel formulation is a potential carrier for efficient topical delivery of terbinafine hydrochloride.