Abstract
Usnic acid (UA) has been studied by its pharmacological properties; however, it presents moderate toxicity, low solubility, and absorption by biological membranes. The aim of this study was to develop poly-ε-caprolactone microsphere polymers containing UA (UA-micro) and evaluate their acute toxicity and anti-inflammatory activity. The microspheres were prepared by multiple emulsion technique (water/oil/water) and characterized by the encapsulation efficiency, particle size, polydispersity index, and zeta potential. The acute toxicity of UA and UA-micro (25–50 mg/kg; p.o.) was evaluated in mice. The anti-inflammatory activity of UA and UA-micro was evaluated by subcutaneous air pouch and carrageenan-induced paw edema in rat, with measurement of inflammatory cytokines and MPO levels. The UA presented encapsulation efficiency of 97.72%, particle size of 13.54 micrometers, polydispersity index of 2.36, and zeta potential of 44.5 ± 2.95 mV. The UA-micro presented lower acute toxicity (LD50 value up to 2000 mg/kg; p.o.) when compared to UA. UA-micro and UA (25 mg/kg) significantly reduced paw volume and decreased MPO levels, whereas only UA-micro (50 mg/kg) reduced significantly IL-1β, TNF-α, and NO levels in inflammatory exudate. These results suggest that controlled release systems, as microspheres, can be a promising alternative to reduce the toxicity of UA, making it a viable compound for inflammation therapy.
Highlights
Inflammation is a complex process involving several cell types and molecular mediators, whose main goals are to isolate, neutralize, and destroy harmful agents, following tissue regeneration stimuli [1]
Nonsteroidal antiinflammatory use in therapeutics has its efficacy, prolonged treatment may be responsible for gastrointestinal side effects, such as superficial mucous membrane alterations, erosive gastritis, and peptic ulcer related to prostaglandins inhibition, produced via COX-1 [2]
Encapsulation efficiency was obtained through three analytic curves, which were prepared from different stock solutions, and adjusted through linear regression analysis
Summary
Inflammation is a complex process involving several cell types and molecular mediators, whose main goals are to isolate, neutralize, and destroy harmful agents, following tissue regeneration stimuli [1]. There is a growing search for new anti-inflammatory agents from natural products, mainly for compounds that have therapeutic and pharmacological potential, reduced side effects, and low cost [3]. Usnic acid (2,6-diacetyl-7,9-dihydroxy-8,9b-diethyl-1,3(2H, 9bH)-benzofuran, C18H16O7), a secondary metabolite isolated from lichens [4, 5], has been highlighted for presenting several biological activities, such as anti-inflammatory, analgesic [6], antimicrobial [7], gastroprotective, antioxidant [8], anticancer [9], and tissue healing activities [10]. Usnic acid has a great variety of biological activities, its utilization as therapeutic agent is not possible yet due to its physicochemical properties, such as low solubility, high toxicity, and impaired interaction with cell barriers [11, 12].
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