Silymarin chitosan-modified penetration enhancer microvesicles as a promising wound healing tool

Silymarin has powerful antioxidant and anti-inflammatory activities which delineate it as a promising wound healing agent, but its physicochemical properties hinder its skin permeation. Therefore, in the current work, we prepared chitosan or hyaluronic acid-modified penetration enhancer vesicles, for enhancing the skin penetration of silymarin. The vesicles ranged in size from 3.08 to 5.73 mu m, depending on the type and amounts of excipients added, with entrapment efficiency reaching 76.15%. They were physically stable as manifested by insignificant changes in particle size, SPAN index, zeta potential and entrapment efficiency values after storage for 6 months. The ex vivo skin deposition experiment demonstrated the high potential of vesicles in accumulating silymarin into the deeper epidermal and dermal layers of the skin compared to silymarin suspension, with the chitosan-modified vesicles being superior to hyaluronic acid-modified vesicles. The chitosan-modified vesicles showed comparable zone of inhibition to gentamycin against Staphylococcus aureus. Results of the in vivo wound healing study revealed that the aforementioned formulation showed 50% reduction of wounds within 7-10 days, which was faster than other experimental groups (untreated control group and marketed product receiving group) which required 10-14 days to show 50% closure of wounds. The collagen deposition areas percent were 35 +/- 1.5%, 23 +/- 1.05%, 12.2 +/- 0.9% and 7.5 +/- 0.86%, and the VEGF expression percentages were 14 +/- 1.3%, 12.1 +/- 1%, 5.2 +/- 0.8% and 1.3 +/- 0.4% for chitosan-modified vesicles, the marketed product, the plain formulation, and the control group respectively. Therefore, it can be concluded that topically applied chitosan-modified vesicles loading silymarin can be a promising wound healing agent.