L-Cysteine-Modified Transfersomes for Enhanced Epidermal Delivery of Podophyllotoxin.

The purpose of this study was to evaluate L-cysteine-modified transfersomes as the topical carrier for enhanced epidermal delivery of podophyllotoxin (POD). L-cysteine-deoxycholic acid (LC-DCA) conjugate was synthesized via an amidation reaction. POD-loaded L-cysteine-modified transfersomes (POD-LCTs) were prepared via a thin membrane dispersion method and characterized for their particle size, zeta potential, morphology, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and in vitro release. Subsequently, in vitro skin permeation and retention, fluorescence distribution in the skin, hematoxylin-eosin staining and in vivo skin irritation were studied. The POD-LCTs formed spherical shapes with a particle size of 172.5 ± 67.2 nm and a zeta potential of -31.3 ± 6.7 mV. Compared with the POD-Ts, the POD-LCTs provided significantly lower drug penetration through the porcine ear skin and significantly increased the skin retention (p < 0.05). Meaningfully, unlike the extensive distribution of the POD-loaded transfersomes (POD-Ts) throughout the skin tissue, the POD-LCTs were mainly located in the epidermis. Moreover, the POD-LCTs did not induce skin irritation. Therefore, the POD-LCTs provided an enhanced epidermal delivery and might be a promising carrier for the topical delivery of POD.

Microemulsion-Based Keratin-Chitosan Gel for Improvement of Skin Permeation/Retention and Activity of Curcumin.

Curcumin (Cur) is a kind of polyphenol with a variety of topical pharmacological properties including antioxidant, analgesic and anti-inflammatory activities. However, its low water solubility and poor skin bioavailability limit its effectiveness. In the current study, we aimed to develop microemulsion-based keratin-chitosan gel for the improvement of the topical activity of Cur. The curcumin-loaded microemulsion (CME) was formulated and then loaded into the keratin-chitosan (KCS) gel to form the CME-KCS gel. The formulated CME-KCS gel was evaluated for its characterization, in vitro release, in vitro skin permeation and in vivo activity. The results showed that the developed CME-KCS gel had an orange-yellow and gel-like appearance. The particle size and zeta potential of the CME-KCS gel were 186.45 ± 0.75 nm and 9.42 ± 0.86 mV, respectively. The CME-KCS gel showed desirable viscoelasticity, spreadability, bioadhesion and controlled drug release, which was suitable for topical application. The in vitro skin permeation and retention study showed that the CME-KCS gel had better in vitro skin penetration than the Cur solution and achieved maximum skin drug retention (3.75 ± 0.24 µg/cm2). In vivo experimental results confirmed that the CME-KCS gel was more effective than curcumin-loaded microemulsion (Cur-ME) in analgesic and anti-inflammatory activities. In addition, the CME-KCS gel did not cause any erythema or edema based on a mice skin irritation test. These findings indicated that the developed CME-KCS gel could improve the skin penetration and retention of Cur and could become a promising formulation for topical delivery to treat local diseases.