Curcumin as an Antioxidant and Anti-inflammatory Agent

Several studies in recent years have demonstrated curcumin as an antioxidant and anti-inflammatory agent the presence of persistent inflammatory stimuli, which interrupt the physiological healing mechanisms.

An ideal biomedical device for wound care should promote the complete regeneration of the injured tissue, effectively restore its biological activity and aesthetic aspect, while reducing inflammation and preventing microbial invasion.1,2 Efforts for achieving this goal are leading to the replacement of traditional passive products with advanced ones.3 Among these, alginate-based dressings are attractive for their capability to release bioactive compounds and to maintain a moist environment around the wound, promoting tissue granulation and re-epithelialization.4-8Typically they are available in form of freeze-dried foams or non-woven microfibers, though great research interest is nowadays devoted towards nanofibrous matrices.

Inflammation is a physiological response to wounding and is required for wound healing to progress. However, excessive or inappropriate inflammation provides an ideal environment for bacterial infiltration and proliferation and may cause serious health problems. So, the prolonged inflammation characterizing the chronic wounds is a promising target for therapeutic interventions

Active agents have been loaded in various of form of carriers such as foams,4 hydrogels,5 films,6 sponges,7 etc., and more recently in the form of polymeric nanofibers.3,8 These polymeric nanofibers have attracted special attention for use in wound dressings due to their very fine diameter, highly porous structure, and so on.1,9 A popular and inexpensive technique for fabricating polymeric nanofibers is electrospinning (ES).3

In particular, nanofibers produced by electrostatic spinning have high potentiality in the wound healing field because their porosity promotes nutrient transport and gas permeation, their morphological organization mimics the native tissue, and their mechanical properties can be engineered.5,9-11 The intrinsic high surface area of nanofibers is also attractive for the delivery of drugs and active agents.2,1

The large surface area of the fiber matrix allow for increased interaction with the tissue, thereby serves as a substrate for the sustained delivery of bioactive molecules as well as to modulate cellular functions during regeneration

Nanofibers fabricated by ES have an extremely large specific surface area, high porosity, and good pore interconnectivity.10,11 These properties are very similar to the natural extracellular matrix structure that supports cell attachment and proliferation.12 It was found that active ingredients can be encapsulated directly into nanofibers by electrospinning a mixture solution containing an agent and a polymer.9,13 Because of their unique properties, the electrospun nanofibers can meet the ideal equirements for wound dressing in that they (1) promote a hemostatic phase, (2) provide a moist environment that stimulates wound healing, (3) protect the wound from bacterial penetration, (4) functionalize dressings by incorporating therapeutic agents, and (5) potentially leave no scars.1,14

The use of biopolymers capable of ES for wound dressing is becoming inevitable because they can generate safe environmental products and easily be washed of the wound surface.1,3 A variety of biopolymers such as PVA,3PLA,11poly(urethane),14 gelatin,15 chitosan,16 polycaprolactone (PCL),17 and some blends of these biopolymers have been electrospun and evaluated for wound dressing.

PCL is a semi-crystalline polymer well known for its nonimmunogenicity, slow biodegradability, and high biocompatibility.17,18 Due to its non-toxic in nature and flexible mechanical properties, PCL is ideal material for wound dressing and tissue engineering.18,19 Although PCL nanofiber mat closely mimics the natural extracellular matrix, its hydrophobicity reduces cell attachment.

addition of PEG in PCL result in  high cell affinity and porous surface of the nanofiber mats  and support cell proliferation.

Chrysin (5,7-dihydroxyflavone) is a natural flavonoid contained in many plant extracts [1]. Many polyphenolic compounds, including chrysin, are known to have multiple biological activities, such as anti-inflammation [2,3], anti-cancer [4,5], anti-oxidation [6,7], and estrogenic effects [6]

Chrysin (5,7-dihydroxyflavone structure shown in Fig. 1), a flavonoid, is the main component of Oroxylum indicum ( Sun et al., 2006), which is one herbal medicine commonly used in China and other East Asian countries, and has been officially listed in the Chinese Pharmacopoeia for a long time (Editorial committee, 1999). Like other flavonoids, chrysin exhibits many biological activities and pharmacological effects, including antioxidant (Chaudhuri et al., 2007), anti-inflammatory (Fishkin and Winslow, 1997), anticancer (Habtemariam, 1997) and antihypertension (Villar et al., 2002). Chrysin also has the potential for clinical and therapeutic applications against the physiological and biochemical effects of aging (Chakraborty et al., 2009).

In spite of these unique biological activities of curcumin, the in vivo stability and bioavailablity of the molecule is very low

Here we show that dressings constituted by electrospun nanofibers of sodium alginate containing lavender essential oil are effective for the treatment of UVB-induced skin injuries. In vitro studies revealed that these entirely natural systems were highly biocompatible and able to inhibit the proliferation of S. aureus. Together with antibacterial activity, the produced alginate based nanofibers expressed a remarkable anti-inflammatory efficacy that was demonstrated in vitro on lipopolysaccharide stimulated human foreskin fibroblasts, and in vivo on rodent model of UVB burns. In particular, a significant decrement of the production of pro-inflammatory cytokines was observed for both cells and animals. Interestingly, no marks of erythema were detected on the skin of the injured animals that were treated with the electrospun dressings, indicating that the treatment promptly stopped the inflammatory response. Differently from other topical preparations for the management of burn wounds, the here described biomedical devices perform dual functions (antibacterial and anti-inflammatory) and, thus, have potentialities to fill the void of multifunctional dressings that the market is still facing

The objective of this study was to develop curcumin loaded PCL nanofibers by the process of electrospinning and to evaluate the biological activity of the curcumin loaded fibers using in vitro and in vivo methods. We investigated the feasibility of developing bead free curcumin loaded PCL nanofibers by controlling the elecrospinning parameters. The bioactivity of encapsulated curcumin in the nanofibers was investigated using various in vitro methods and comparisons were made against the corresponding PCL nanofibers. Finally, the in vivo efficacy of the curcumin loaded PCL fibers vs PCL fibers was evaluated using healing impaired diabetic mouse model.

in view of the high level of oxidative stress and persistent inflammation associated with delayed healing in diabetic wounds, the present study was conducted to investigate the temporal wound healing potential of topically applied curcumin
in diabetic rats

The increased oxidative stress is one of the most common complications for the delayed wound healing in diabetics [3]. Therefore, reduction/ termination of the persistent inflammation and elimination of free radicals by the introduction of an anti-inflammatory agent and antioxidant into the treatment of wounds could be an important strategy to improve
healing of diabetic wounds.