BACKGROUND: Simultaneous anti-Cutibacterium acnes and anti-inflammatory actions are highly beneficial in treating acne vulgaris. In this study, we present novel anti-acne nanovesicles based on liposomes loaded with proteinase K (PK), retinoic acid (RA), and soyaethyl morpholinium ethosulfate (SME) to achieve an effective and safe treatment. MATERIALS AND METHODS: This study examined in vitro planktonic and biofilm C. acnes elimination, as well as the keratinocyte proliferation suppression by liposomes. The multifunctional liposomes for treating C. acnes in mice were also evaluated. RESULTS: We acquired multifunctional liposomes with a size of 71 nm and zeta potential of 31 mV. The antimicrobial activity of SME was enhanced after liposomal encapsulation according to the reduction of minimum bactericidal concentration (MBC) by 6-fold. The multifunctional liposomes exhibited a synergistically inhibitory effect on biofilm C. acnes colonization compared with the liposomes containing PK or those containing SME individually. The adhesive bacterial colony in the microplate was lessened by 62% after multifunctional liposome intervention. All liposomal formulations tested here demonstrated no cytotoxicity against the normal keratinocytes but inhibited C. acnes-stimulated cell hyperproliferation. The in vitro scratch assay indicated that the liposomal RA-but not free RA-restrained keratinocyte migration. The animal study showed that free RA combined with SME and multifunctional nanovesicles had a similar effect on diminishing C. acnes colonies in the skin. On the other hand, liposomes exhibited superior performance in recovering the impaired skin barrier function than the free control. We also found that RA-loaded nanovesicles had greater skin tolerability than free RA. CONCLUSION: The cationic liposomes containing dual PK and RA represented a potential treatment to arrest bacterial infection and associated inflammation in acne.
- MeSH
- acne vulgaris * MeSH
- antibakteriální látky farmakologie MeSH
- biofilmy MeSH
- endopeptidasa K farmakologie MeSH
- keratinocyty MeSH
- liposomy * farmakologie MeSH
- myši MeSH
- proliferace buněk MeSH
- tretinoin farmakologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Background: Antimicrobial submicrometer particles are being studied as promising interventions against a wide range of skin conditions, such as fungal or bacterial infections. Aims: To submicronize chloroxine, the crystalline compound 5,7-dichloro-8-hydroxyquinoline, by nanoprecipitation and characterize the resulting assemblies. Methods: The chloroxine particles were stabilized by a nonionic surfactant and were studied by a broth microdilution assay against 20 medically important bacteria and fungi. The intervention was studied using a murine model of skin irritation. Results & conclusion: Chloroxine nanoparticles with a diameter of 600-800 nm exhibit good tolerability in terms of skin irritation in vivo and good antimicrobial activity. Thus, the fabricated formulation shows great promise for interventions for both cutaneous infection control and prophylaxis.
To improve the treatment of psoriasiform inflammation, we developed actively targeted nanocarriers loaded with the phosphodiesterase 4 inhibitor AN2728. Methods: Phospholipid-poly(lactic-co-glycolic acid) nanohybrids were prepared and conjugated with monovalent anti-desmoglein 3 antibody to bind keratinocytes. Results: The actively targeted nanohybrids were 229 nm in mean size with a nearly neutral surface charge. Flow cytometry and confocal microscopy showed a 9-fold increase in keratinocyte uptake of targeted nanohybrids relative to non-targeted nanoparticles. The nanoparticles localized mainly in lysosomes after internalization. AN2728-loaded antibody-conjugated nanocarriers inhibited cytokine/chemokine overexpression in activated keratinocytes without affecting cell viability. The targeted nanohybrids also suppressed neutrophil migration by reducing CXCL1 and CXCL2 release from keratinocytes. Following subcutaneous administration in mice, the nanohybrids distributed to the epidermis and hair follicles. In a psoriasis-like skin mouse model, the actively targeted nanoparticles were superior to free drug and non-targeted nanoparticles in mitigating skin inflammation. Intervention with the targeted nanosystem reduced the epidermal thickness of the psoriasiform lesion from 191 to 42 µm, decreased the Psoriasis Area Severity Index by 74%, restored barrier function, and returned chemokine levels to baseline. Conclusions: Our developed nanosystem was safe and demonstrated efficient targeting properties for the treatment of cutaneous inflammation.
- MeSH
- bicyklické sloučeniny heterocyklické aplikace a dávkování farmakologie MeSH
- buněčné linie keratinocytů HaCaT MeSH
- chemokin CXCL1 účinky léků imunologie MeSH
- chemokin CXCL2 účinky léků imunologie MeSH
- chemotaxe účinky léků MeSH
- desmoglein 3 imunologie MeSH
- epidermis MeSH
- fosfolipidy * MeSH
- imunokonjugáty farmakologie MeSH
- inhibitory fosfodiesterasy 4 aplikace a dávkování farmakologie MeSH
- keratinocyty účinky léků imunologie MeSH
- kopolymer kyseliny glykolové a mléčné * MeSH
- lidé MeSH
- lyzozomy metabolismus ultrastruktura MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- nanočástice * MeSH
- neutrofily účinky léků MeSH
- nosiče léků MeSH
- protilátky imunologie MeSH
- psoriáza imunologie patologie MeSH
- sloučeniny boru aplikace a dávkování farmakologie MeSH
- systémy cílené aplikace léků MeSH
- vlasový folikul MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Aim: We aimed to develop nanoemulsions containing phosphodiesterase 4 inhibitor rolipram with different droplet sizes, to evaluate the anti-inflammatory effect against activated neutrophils and a related lung injury. Materials & methods: We prepared nanoemulsions of three different sizes, 68, 133 and 188 nm. Results: The nanoemulsion inhibited the superoxide anion but not elastase release in primary human neutrophils. The large-sized nanoemulsions were mostly internalized by neutrophils, resulting in the reduction of intracellular Ca2+ half-life. The peripheral organ distribution of near-infrared dye-tagged nanoemulsions increased, following the decrease in droplet diameter. Rolipram entrapment into intravenous nanoemulsions ameliorated pulmonary inflammation. The smallest droplet size showed improvement, compared with the largest size. Conclusion: We established a foundation for the development of nanoemulsions against inflamed lung disease.
- MeSH
- antiflogistika * farmakologie MeSH
- emulze MeSH
- lidé MeSH
- nanomedicína MeSH
- neutrofily účinky léků MeSH
- zánět * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Tuberculosis represents a major global health problem for which improved approaches are needed to shorten the course of treatment and to combat the emergence of resistant strains. The development of effective and safe nanobead-based interventions can be particularly relevant for increasing the concentrations of antitubercular agents within the infected site and reducing the concentrations in the general circulation, thereby avoiding off-target toxic effects. In this work, rifampicin, a first-line antitubercular agent, was encapsulated into biocompatible and biodegradable polyester-based nanoparticles. In a well-established BALB/c mouse model of pulmonary tuberculosis, the nanoparticles provided improved pharmacokinetics and pharmacodynamics. The nanoparticles were well tolerated and much more efficient than an equivalent amount of free rifampicin.
- MeSH
- antibiotika tuberkulostatická * farmakokinetika MeSH
- antituberkulotika MeSH
- Mycobacterium tuberculosis * MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- nanostruktury MeSH
- nosiče léků MeSH
- rifampin * farmakokinetika MeSH
- tuberkulóza * farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
