Use of N-oxide and cationic surfactants to enhance antioxidant properties of (+)-usnic acid loaded liposomes

Abstract

The influence of the presence of synthetic structurally related N-oxide and corresponding cationic surfactants with different chain lengths on the properties of 1,2-dimyristoyl-sn-glycero-3-phosphocholine liposomes was investigated. Their potentiality as delivery systems of (+)-usnic acid was also evaluated by studying its entrapment efficiency and its antioxidant activity. In fact, (+)-usnic acid has many pharmacological properties that, as many natural substances, are often strictly linked to their antioxidant power. N-oxide surfactants can enhance this property and improve the efficacy of the system. Based on this premise, we verified how and to what extent the molecular structure of liposomes components affects this effect: the best antioxidant effectiveness was observed when (+)-usnic acid was included in liposomes containing the N-oxide surfactant with C14 alkyl chain. Our results underline the importance of the hydrophilic/hydrophobic balance of the monomer in determining the properties of the aggregates in which it is included.

Nano- and Microcarriers as Drug Delivery Systems for Usnic Acid: Review of Literature

“…Pharmaceutics 2020, 12, x 4 of 24 activity, concluding that, more than the charge or the chain length, the combination of both these parameters was fundamental in affecting liposomes physicochemical properties and their ability of influencing the antioxidant effectiveness of usnic acid. Although both studies indicated incorporation of usnic acid into functionalized nanoliposomes to enhance its biological properties, the investigated liposomal suspensions were found to be stable for at least two weeks [19] or less [20], and this issue should be addressed prior to their potential practical usage in the treatment of infections/oxidative stress-related diseases.…”

“…Details of studies concerning usnic acid loaded into nanoliposomes are presented below. Promotion of (+)-usnic acid penetration in biofilm matrix with a consequent increase of antimicrobial activity against S. epidermidis [19] Oxidative stress-related diseases DMPC, Chol and L-prolinol derived surfactants ∼100 from 52 ± 2 to 77 ± 2 Aggregation after two weeks Enhancement of antioxidant properties of (+)-usnic acid [20] Dressing for burn wounds * PC, collagen, PEG/PG 70 n.a. n.a.…”

“…Two recently published papers discussed the usage of positively charged liposomes, which were functionalized in order to enhance biological effects of the encapsulated usnic acid [19,20]. To this end, physicochemical characterization of the produced liposomes was performed, and afterwards the influence of the lipid components used for their production (differing in chain length, size and charge of their headgroups, saturation or substituents) and/or method of usnic acid loading to the biological activities of usnic acid was investigated.…”

“…In another study, impact of an N-oxide moiety in the phospholipid bilayer to the antioxidative activity of usnic acid entrapped in the liposomes was investigated, bearing in mind that the presence of N-oxide in the molecule structure was found to mimic the activity of superoxide dismutase, and also that aggregates of surfactants carrying this moiety can affect the antioxidant activity of a molecule they include [20]. Additionally, the effect of the presence of the quaternary ammonium moiety, instead of N-oxide, and also different chain lengths (C12, C14 and C16) in both groups of ligands attached to the surface of liposomes loaded with usnic acid were assessed ( Figure 3b).…”

“…Interestingly, at the end of the experiment, the treated wounds were in an advanced healing phase, confirming the ability of this compound to effect the inflammatory response during wound healing, attenuating the expression of TNF-a, IL-6, IL-8 and macrophage inflammatory protein-2 (MIP-2), as well as improving the level of IL-10. Taking into Although both studies indicated incorporation of usnic acid into functionalized nanoliposomes to enhance its biological properties, the investigated liposomal suspensions were found to be stable for at least two weeks [19] or less [20], and this issue should be addressed prior to their potential practical usage in the treatment of infections/oxidative stress-related diseases.…”