Poly‐ε‐Caprolactone Microsphere Polymers Containing Usnic Acid: Acute Toxicity and Anti‐Inflammatory Activity

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.

Mitigation of Hydrophobicity-Induced Immunotoxicity by Sugar Poly(orthoesters)

“…No other adverse clinical symptoms were observed. These results further confirmed that our carbohydrate-based NPs did not cause long-term immunotoxicity, as such a toxicity could result in malaise and altered animal behavior, leading to body weight reduction …”

“…These results further confirmed that our carbohydrate-based NPs did not cause long-term immunotoxicity, as such a toxicity could result in malaise and altered animal behavior, leading to body weight reduction. 33 In conclusion, we designed and synthesized a series of new NP systems having SPOE as the hydrophobic component. Our studies, especially the parallel studies with PLA and PCL-based NP systems, indicate that the carbohydrate-based polymers can largely mitigate the hydrophobicity-induced immunotoxicity; therefore, they may, as low immunotoxic biomaterials, find applications for various biomedical and clinical studies.…”

Toxicity of Usnic Acid: A Narrative Review

“…In another study, the toxicity of encapsulated UA was evaluated in vitro on HEp-2 cell lines using the MTT method, confirming a reduction of toxicity, compared to free UA [71]. Other authors confirmed these results, including a study that, besides assessing an increase of the anti-inflammatory effects of UA-loaded polymeric microparticles, and also reported a marked reduction of acute toxicity [75].…”

In Vitro and In Vivo Wound Healing and Anti‐Inflammatory Activities of Babassu Oil (Attalea speciosa Mart. Ex Spreng., Arecaceae)

“…The left ear samples were processed for histological and histomorphometric evaluation, while the right ear samples were homogenized in 50 mM phosphate buffer containing 0.5% hexadecyltrimethylammonium bromide (HTAB) for the quantification of myeloperoxidase activity [ 21 ].…”