Self-Associating Polymers Chitosan and Hyaluronan for Constructing Composite Membranes as Skin-Wound Dressings Carrying Therapeutics

Abstract

Chitosan, industrially acquired by the alkaline N-deacetylation of chitin, belongs to β-N-acetyl-glucosamine polymers. Another β-polymer is hyaluronan. Chitosan, a biodegradable, non-toxic, bacteriostatic, and fungistatic biopolymer, has numerous applications in medicine. Hyaluronan, one of the major structural components of the extracellular matrix in vertebrate tissues, is broadly exploited in medicine as well. This review summarizes that these two biopolymers have a mutual impact on skin wound healing as skin wound dressings and carriers of remedies.

Keywords: MitoQ; SkQ; antioxidants; chitin; hyaluronic acid; l-(+)-ergothioneine; resveratrol; wound healing.

Scheme 1

Concentration of a drug (blue; axis Y) during the period of treatment (axis X) must be in a range of effective treatment level of a drug (area marked in green), whereas it must never be in the range of levels of a drug, which is toxic (area marked in red) and should not be in the range of therapeutically ineffective level of a drug (area marked in yellow) in the site of the drug action. The time interval between two consecutive applications is indicated—i.

Figure 1

Top panel: The two self-associating biopolymers, namely a polyanionic high-molar-mass hyaluronan (purple) and a polycationic chitosan (green) yield a complex coacervate/polyionic complex hydrogel. Bottom panel: The co-application of an active principle (blue dots) in the formation of a three-component viscous solution, i.e., the material used to construct a composite membrane.

Figure 2

Left panel: Severe ulcers of the man’s leg, middle panel: Schematic application of a composite membrane consisting of a scaffold impregnated with self-associated macromolecules of chitosan (green) and high-molar-mass hyaluronan (purple) with a molecularly dispersed wound healing active medical principle (blue, a proper MTA), right panel: Result of a few-day treatment of the patient’s ulcers. Adapted with permission from ref. [75].

Scheme 2

Left panel schematically illustrates release of a hydrophobic low-molar-mass compound from a lipophilic depot. Right panel demonstrates the situation when the hydrophilic compound is released from the hydrophilic reservoir. s. c. stratum corneum = thickness 10–15 μm e. epidermis = 150 μm d. dermis = 1–2 mm h. hypodermis/subcutis.

Scheme 3

The two electron reductive reactions of MitoQ (top reaction panel) or SkQ (bottom reaction panel) within a mitochondrion.

Scheme 4

Reaction of initiation: (a) an intact HA macromolecule reacts with ^●OH radical; (b) formation of an intermediate, i.e., a C-centered HA macroradical. Reactions of propagation and of transfer of the free-radical center; (c) formation of a peroxy-type macroradical; (d,e) generation of a HA hydroperoxide and a highly unstable alkoxy-type macroradical. Reaction yielding fragments: (f) an alkoxy-type macroradical and a HA-like macromolecule bearing a terminal C=O group. Both fragments have reduced molar mass.

Scheme 5

The flow-chart representing one possible route by which trans-resveratrol acts like the so-called HAT—hydrogen atom transferring compound. More complex reaction flow-charts can be found by readers in the ref. [87].

Scheme 6

Thione (left) and thiol (right) forms of l-(+)-ergothioneine.

Figure 3

Redox stress. Adapted from [89].