Recently, the polyion complex (PIC) micelle has been suggested as a promising carrier system for peptide and proteins. However, its utilities are limited by its sensitivity to the environment such as dilution and ionic strength of the solution. In this study, to overcome these obstructions, PIC micelles prepared from an anionic block copolymer, poly(ethylene glycol)-poly(alpha,beta-aspartic acid), and a cationic protein, trypsin, were cross-linked with glutaraldehyde through the Schiff base formation. On the basis of a light scattering technique, the results revealed an efficient resistance of the cross-linked PIC micelle to a high salt concentration, which was a key parameter controlling the structure of the PIC micelles. Moreover, the stability of trypsin after cross-linking was remarkably improved. Evidently, as a bionanoreactor and/or bionanoreservoir, the PIC micelles entrapping protein molecules in the cross-linked core reveal an improved stability, allowing their wide application in the fields of biotechnology and pharmaceutical sciences.

Existing therapies for rheumatoid arthritis and other autoimmune diseases are not Ag specific, which increases the likelihood of systemic toxicity. We show that egg phosphatidylcholine liposomes loaded with Ag (OVA or methylated BSA) and a lipophilic NF-κB inhibitor (curcumin, quercetin, or Bay11-7082) suppress preexisting immune responses in an Ag-specific manner. We injected loaded liposomes into mice primed with Ag or into mice suffering from Ag-induced inflammatory arthritis. The liposomes targeted APCs in situ, suppressing the cells’ responsiveness to NF-κB and inducing Ag-specific FoxP3+ regulatory T cells. This regulatory mechanism suppressed effector T cell responses and the clinical signs of full-blown Ag-induced arthritis. Thus, liposomes encapsulate Ags and NF-κB inhibitors stably and efficiently and could be readily adapted to deliver Ags and inhibitors for Ag-specific suppression of other autoimmune and allergic diseases.

BackgroundThe emergence of drug resistant pathogens becomes a crucial problem for infectious diseases worldwide. Among these bacteria, Pseudomonas aeruginosa is one of which highly resists to many currently used drugs and becomes a major concern in public health. Up till now, the search for potential antimicrobial agents has been still a challenge for researchers.MethodsBroth microdilution assay was used to determine minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of the essential oils and antibiotics against P. aeruginosa. Inhibition activity of the essential oils under vapor condition was examined to obtain the minimum inhibitory dose (MID). Time-kill assay included in this study was performed according to CLSI guideline. Bioautographic assay was used to detect active components of the essential oil. Synergistic effect with currently used antibiotics was further examined by checkerboard assay.Results and DiscussionIn this study, a variety of essential oils were examined for anti-multidrug resistant P. aeruginosa (MDR-PA) activity, of which cinnamon bark oil showed the strongest antimicrobial activity against all clinical-isolated MDR-PA strains with MIC of 0.0562–0.225 % v/v and MBC of 0.1125–1.8 % v/v. Bioautographic results demonstrated that the active compounds of cinnamon bark oil were cinnamaldehyde and eugenol which showed strong inhibitory effect against P. aeruginosa. Interestingly, cinnamaldehyde, a major constituent of cinnamon bark oil, possessed stronger antimicrobial effect to P. aeruginosa than eugenol. Under gaseous condition, cinnamon bark oil and cinnamaldehyde showed antibacterial activity against MDR-PA strains with MID of 0.5–1 mg/L. Moreover, combination of cinnamon bark oil or cinnamaldehyde with currently used antibiotics was further studied by checkerboard assay to examine synergistic interactions on clinically isolated MDR-PA strains. Cinnamon bark oil and cinnamaldehyde combined with colistin demonstrated synergistic rates at 16.7 and 10 %, respectively.ConclusionThese results indicated that cinnamon bark oil and cinnamaldehyde might be active natural compounds which could be further examined as alternative treatment for multidrug-resistant P. aeruginosa infection.

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