RESUMEN
Topical application is an important administration route for drugs requiring local action on the skin, thereby avoiding their systemic absorption and adverse side effects. Rosmarinus officinalis L. (syn. Salvia rosmarinus Spenn.), popularly known as rosemary, is an aromatic plant with needle-like leaves belonging to the Lamiaceae family. Rosemary has therapeutic properties and has been used in the folk medicine, pharmaceutical, and cosmetics industries, mainly for its antioxidant and anti-inflammatory properties, which are attributed to the presence of carnosol/carnosic and ursolic acids. The therapeutic use of rosemary has been explored for the treatment of inflammatory diseases; however, other uses have been studied, such as wound healing and skin cancer and mycoses treatments, among others. Besides it therapeutic uses, rosemary has potential applications in cosmetic formulations and in the treatment of pathological and non-pathological conditions, such as cellulite, alopecia, ultraviolet damage, and aging. This review aims to critically discuss the topical applications of rosemary found in the literature while also offering relevant information for the development of topical formulations of its bioactive compounds.
RESUMEN
Topical nitric oxide (NO) delivery has been shown to accelerate wound healing. However, delivering NO to wounds at appropriate rates and doses requires new biomaterial-based strategies. Here, we describe the development of supramolecular interpolymer complex hydrogels comprising PEO-PPO-PEO (F127) micelles embedded in a poly(acrylic acid) (PAA) matrix, with S-nitrosoglutathione (GSNO) molecules dissolved in the hydrophilic domain. We show that PAA:F127/GSNO hydrogels start releasing NO upon hydration at rates controlled by their rates of water absorption. SAXS measurements indicate that the supramolecular structure of the hydrogels retains long-range order domains of F127 micelles. The PAA/F1227 hydrogels displayed dense morphologies and reduced rates of hydration. The NO release rates remain constant over the first 200â¯min, are directly correlated with the hydration rates of the PAA:F127/GSNO hydrogels, and can be modulated in the range of 40â¯nmol/gâ¯h to 1.5⯵mol/gâ¯h by changing the PAA:F127 mass ratio. Long-term NO-release profiles over 5â¯days are governed by the first-order exponential decay of GSNO, with half-lives in the range of 0.5-3.4â¯days. A preliminary in vivo study on full-thickness excisional wounds in mice showed that topical NO release from the PAA:F127/GSNO hydrogels is triggered by exudate absorption and leads to increased angiogenesis and collagen fiber organization, as well as TGF-ß, IGF-1, SDF-1, and IL-10 gene expressions in the cicatricial tissue. In summary, these results suggest that hydration-controlled NO release from topical PAA:F127/GSNO hydrogels is a potential strategy for enhancing wound healing. STATEMENT OF SIGNIFICANCE: The topical delivery of nitric oxide (NO) to wounds may provide significant beneficial results and represent a promising strategy to treat chronic wounds. However, wound dressings capable of releasing NO after application and allowing the modulation of NO release rates, demand new platforms. Here, we describe a novel strategy to overcome these challenges, based on the use of supramolecular poly(acrylic acid) (PAA):F127 hydrogels charged with the NO donor S-nitrosoglutathione (GSNO) from whereby the NO release can be triggered by exudate absorption and delivered to the wound at rates controlled by the PAA:F127 mass ratio. Preliminary in vivo results offer a proof of concept for this strategy by demonstrating increased angiogenesis; collagen fibers organization; and TGF-ß, IGF-1, SDF-1, and IL-10 gene expressions in the cicatricial tissue after topical treatment with a PAA:F127/GSNO hydrogel.
