Development of thymol-loaded polymeric films designed as wound dressing materials: Physical, antioxidant, antibacterial, cytocompatibility, and wound healing properties

Wound dressing materials that are in direct contact with the wound play an important role in wound management. They must be carefully selected to suit the specific wound type and promote healing. Modern wound dressing materials are favored because they are more beneficial than traditional ones. Traditional wound dressing materials, like gauze, plasters, and bandages, are typically unable to provide a moist environment to the wound. An ideal wound dressing should be biocompatible, flexible, easily applied, protect the wound bed, remove excess exudate, prevent inflammation, and also promote wound healing process. In addition to having the ideal wound dressing features, the modern generation of wound dressings has been carefully designed to deliver active pharmaceutical components to the wound site. The modern wound dressings are available in the forms of films, hydrogels, hydrocolloids, hydroactives, foams, alginates and hydrofibers [1,2].

Polymeric films are frequently used in the medical sector to treat wounds as physical barriers that aid in reducing inflammation, accelerating recovery, and protecting the wound's environment. The biocompatibility, non-invasiveness, providing a moist environment, and possibility for antimicrobial treatment of polymeric films have made them widely desirable. These films also have significant advantages in terms of their physical characteristics, such as transparency, flexibility, and gas exchange capacity [[2], [3], [4]]. Biopolymers have emerged as an ideal choice for preparing wound dressing polymeric films due to their excellent biomedical properties. These include biocompatibility, biodegradability, non-toxicity, non-immunogenicity, antibacterial features, and wound healing properties [5,6]. Regarding the importance of wound dressing films, the research was done to develop thymol integrated kappa carrageenan (CARR)/pullulan (PUL) based biopolymeric films to enhance the wound healing effect.

The PUL biopolymer is a linear glycosidic polysaccharide produced from the polymorphic fungus Aureobasidium pullulans, which is of great interest in the food, pharmaceutical, and biomedical industries [7,8]. The distinct physical and chemical features of PUL are attributed to the presence of α-(1 → 4) and α-(1 → 6) glycosidic linkages [9]. PUL is an exo-polysaccharide that is biodegradable, tasteless, odorless, edible, adhesive, non-immunogenic, non-toxic, non-carcinogenic and non-mutagenic [9]. Also, it can be used in the preparation of thin biodegradable films [7].

Carrageenan is a biopolymer obtained by extraction of red seaweeds, where alternating units of d-galactose and 3, 6-anhydro-galactose (3, 6-AG) are formed by −1, 3 and −1, 4-glycosidic bonds. It is the general name of a group of sulfated polysaccharides with high molecular weight and linear structure [10,11]. Food, cosmetics, pharmaceuticals, and textile formulations are just some of the industries that utilize carrageenan. CARR, one of the three main types of carrageenan that vary in their degree of sulfation, is the polysaccharide fraction with only one sulfate group per disaccharide repeating unit [10]. CARR can be used to develop edible films and coatings. The properties such as wide availability in nature, low cost, non-toxicity, anticoagulant properties, biocompatibility, biodegradability, lack of inflammatory response and antiviral activity make CARR attractive for pharmaceutical applications [12,13].

Thymol (2-isopropyl-5-methylphenol) is a phenolic monoterpene rich essential oil that extracted from Lamiaceae family plants. Thymol's potential antibacterial, antioxidant, anticarcinogenic, and anti-inflammatory properties have led to an extensive range of functional uses in the food, pharmaceuticals, and cosmetic industries [[14], [15], [16]]. According to the research presented in the literature, the films incorporated with thymol, a herbal medicine, have promising results as wound dressings [[17], [18], [19], [20]].

In the study, the solvent casting method was used to prepare films from PUL and CARR biopolymers that contained thymol. The films' structural and morphological characteristics, swelling and hydrolytic degradation rates, water vapor transmission rates, and mechanical properties were reviewed. Also, the films were characterized in terms of their antibacterial and antioxidant properties. It was determined that the films had the potential to be employed as wound dressing material after analyzing the results of the in vitro cytotoxicity and in vitro wound scratch tests.

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