Curcumin-In-Deformable Liposomes-In-Chitosan-Hydrogel as a Novel Wound Dressing

Abstract

A liposomes-in-hydrogel system as an advanced wound dressing for dermal delivery of curcumin was proposed for improved chronic wound therapy. Curcumin, a multitargeting poorly soluble active substance with known beneficial properties for improved wound healing, was incorporated in deformable liposomes to overcome its poor solubility. Chitosan hydrogel served as a vehicle providing superior wound healing properties. The novel system should assure sustained skin delivery of curcumin, and increase its retention at the skin site, utilizing both curcumin and chitosan to improve the therapy outcome. To optimize the properties of the formulation and determine the effect of the liposomal charge on the hydrogel properties, curcumin-containing deformable liposomes (DLs) with neutral (NDLs), cationic (CDLs), and anionic (ADLs) surface properties were incorporated in chitosan hydrogel. The charged DLs affected the hydrogel's hardness, cohesiveness, and adhesiveness. Importantly, the incorporation of DLs, regardless of their surface charge, in chitosan hydrogel did not decrease the system's bioadhesion to human skin. Stability testing revealed that the incorporation of CDLs in hydrogel preserved hydrogel´s bioadhesiveness to a higher degree than both NDLs and ADLs. In addition, CDLs-in-hydrogel enabled the most sustained skin penetration of curcumin. The proposed formulation should be further evaluated in a chronic wound model.Curcumin has been proposed as one of the most promising [5]. Moreover, curcumin is a molecule able to active multiple pathways, contributing to improved wound healing [6]. The antioxidant, anti-inflammatory, and anti-bacterial properties of this pleiotropic molecule need to be more utilized [7,8]. Although curcumin is a very promising molecule to be included in wound dressings, its hydrophobicity, extensive metabolism, and limited skin penetration often hamper its wider use [9]. We have recently proven that curcumin, a multitargeting active substance, exhibits superior anti-inflammatory properties when incorporated in tailored deformable liposomes [10]. In this work, we went a step further in the development of curcumin-based wound dressings and combined the beneficial properties of curcumin as an active moiety and chitosan hydrogel as a superior vehicle to form a bioactive wound dressing targeting the treatment of chronic wounds.An ideal dressing should assure an enhanced therapeutic outcome and reduction of pain accompanied with wound dressing changes [11]. Among the possible material to be used in the manufacturing of bioactive dressings, natural polymer-based wound dressings, such as hydrogels, represent promising advanced delivery systems with a low risk of toxicity and side effects due to their biodegradability and biocompatibility [12,13]. Hydrogels mimic the biochemical, biomechanical, and structural features of the extracellular matrix (ECM), serving as superior matrices for wound treatment [13,14]. Hydrogels additionally possess good bioadhesiveness that can contribute to a prolonged retention...

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