Fucoidan-Coated Liposomes: A Target System to Deliver the Antimicrobial Drug Usnic Acid to Macrophages Infected with Mycobacterium tuberculosis.

The present study describes the use of fucoidan, a negative sulfated polysaccharide, as a coating material for the development of liposomes targeted to macrophages infected with Mycobacterium tuberculosis. First, fucoidan was chemically modified to obtain a hydrophobized-fucoidan derivative (cholesteryl-fucoidan) using a two-step microwave-assisted (µW) method. The total reaction time was decreased from 14 hours to 1 hour while maintaining the overall yield. Cholesterylfucoidan was then used to prepare surface-modified liposomes containing usnic acid (UA-LipoFuc), an antimicrobial lichen derivative. UA-LipoFuc was evaluated for mean particle size, polydispersity index (PDI), surface charge (ζ), and UA encapsulation efficiency. In addition, a cytotoxicity study, competition assay and an evaluation of antimycobacterial activity against macrophages infected with M. tuberculosis (H37Ra) were performed. When the amount of fucoidan was increased (from 5 to 20 mg), vesicle size increased (from 168 ± 2.82 nm to 1.18 ± 0.01 µm). Changes in from +20 ± 0.41 mV for uncoated liposomes to -5.41 ± 0.23 mV for UA-LipoFuc suggested that the fucoidan was placed on the surface of the liposomes. UA-LipoFuc exhibited a lower IC50 (8.26 ± 1.11 µM) than uncoated liposomes (18.37 ± 3.34 µM), probably due to its higher uptake. UA-LipoFuc5 was internalized through the C-type carbohydrate recognition domain of the cell membrane. Finally, usnic acid, both in its free form and encapsulated in fucoidan-coated liposomes (UA-LipoFuc5), was effective against infected macrophages. Hence, this preliminary investigation suggests that encapsulated usnic acid will aid in further studies related to infected macrophages and may be a potential option for tuberculosis treatment.

Poly(anhydride) nanoparticles containing cashew nut proteins can induce a strong Th1 and Treg immune response after oral administration.

Cashew nut allergy is the second most commonly reported tree nut allergy. Traditional allergen immunotherapy presents several clinical drawbacks that can be reduced by using nanoparticles-basedallergen-delivery systems, modulating the immune response towards a protective one. In this context, the goal of this work was to assess the potential of poly(anhydride) nanoparticles (NP) for cashew nut oral immunization. Cashew nut allergens-loaded nanoparticles (CNE-NP) were prepared by solvent displacement method. After nanoparticles characterization, oral immunomodulation ability was evaluated in BALB/c mice. Our results demonstrated that CNE-NP induced a higher Th1/Th2 ratio in comparison with animals immunized with free cashew nut proteins. Indeed, a decrease in splenic Th2 cytokines (IL-4, IL-5, and IL-13), and an enhancement of pro-Th1 (IL-12 and IFN-γ) and regulatory (IL-10) cytokines was observed. Furthermore, mice orally immunized with CNE-NP presented an increased expansion of CD4+ T regulatory cells, such as CD4+Foxp3+ and CD4+LAP+, in the mesenteric lymph nodes. In conclusion, oral immunization with a single dose of poly(anhydride) nanoparticles loaded with cashew nut proteins leaded to a pro-Th1 and Treg immune response. Furthermore, their immunomodulatory properties could be introduced as a new approach for management of cashew nut allergy.

Cationic liposomes containing antioxidants reduces pulmonary injury in experimental model of sepsis: Liposomes antioxidants reduces pulmonary damage.

The intracellular redox state of alveolar cells is a determining factor for tolerance to oxidative and pro-inflammatory stresses. This study investigated the effects of intratracheal co-administration of antioxidants encapsulated in liposomes on the lungs of rats subjected to sepsis. For this, male rats subjected to sepsis induced by lipopolysaccharide from Escherichia coli or placebo operation were treated (intratracheally) with antibiotic, 0.9% saline and antioxidants encapsulated or non-encapsulated in liposomes. Experimental model of sepsis by cecal ligation and puncture (CLP) was performed in order to expose the cecum. The cecum was then gently squeezed to extrude a small amount of feces from the perforation site. As an index of oxidative damage, superoxide anions, lipid peroxidation, protein carbonyls, catalase activity, nitrates/nitrites, cell viability and mortality rate were measured. Infected animals treated with antibiotic plus antioxidants encapsulated in liposomes showed reduced levels of superoxide anion (54% or 7.650±1.263 nmol/min/mg protein), lipid peroxidation (33% or 0.117±0.041 nmol/mg protein), protein carbonyl (57% or 0.039 ± 0.022 nmol/mg protein) and mortality rate (3.3%), p value <0.001. This treatment also reduced the level of nitrite/nitrate and increased cell viability (90.7%) of alveolar macrophages. Taken togheter, theses results support that cationic liposomes containing antioxidants should be explored as coadjuvants in the treatment of pulmonary oxidative damage.