Combination of Microneedles and MF59 Adjuvant as a Simple Approach to Enhance Transcutaneous Immunization

2020 ◽  
Vol 16 (12) ◽  
pp. 1776-1786
Author(s):  
Qin Yu ◽  
Yanping Huang ◽  
Congcong Zhu ◽  
Xiying Wu ◽  
Zongguang Tai ◽  
...  
Keyword(s):  
Simple Approach ◽  
Preparation Technique ◽  
Intact Skin ◽  
Antigen Uptake ◽  
Water Emulsion ◽  
Safety Issues ◽  
Oil In Water ◽  
Transcutaneous Immunization

MF59, an oil-in-water nanoemulsion, has been used in licensed seasonal influenza vaccines for many years. Administration of such vaccines by injection is associated with pain and safety issues. Here, we evaluated the potential of administering MF59 via a transcutaneous route with antigen loading (either encapsulated into or mixed with MF59) to intact or microneedle-pretreated skin. In addition to commercial MF59, we also prepared a nanoemulsion to encapsulate hydrophilic antigens by mimicking the formulation and preparation technique of MF59. The nanoemulsion was prepared using a water-in-oil-in-water emulsion method, and was similar to MF59 in composition, particle size, and morphology. Compared with the intact skin group, the microneedle-pretreated group showed significant enhanced antigen penetration. In vivo transcutaneous immunization analysis showed that the MF59-adjuvant influenza vaccine elicited approximately 3–5 times higher hemagglutination inhibition titers than the influenza solution alone in BALB/c mice after microneedle pretreatment. The intact skin group showed negative immune results at the same dose, suggesting that microneedle pretreatment was critical for efficient delivery of antigens, to obtain strong immune responses. Furthermore, the loading method (encapsulation or mixing with the vehicle) did not affect the dermal penetration or transcutaneous immunization of antigens on microneedle-pretreated skin. Moreover, in vitro cellular assays showed that MF59 facilitated the maturation of dendritic cells and enhanced antigen uptake by antigen-presenting cells. In conclusion, the combination of microneedle pretreatment and mixing of MF59 with antigen provides a simple approach to enhance transcutaneous immunization.

scholarly journals Optimizing the Process Design of Oil-in-Water Nanoemulsion for Delivering Poorly Soluble Cannabidiol Oil

Processes ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 1180
Author(s):  
Agnieszka Lewińska
Keyword(s):  
Process Design ◽  
Hacat Keratinocytes ◽  
Degree Of Hydration ◽  
Skin Cell ◽  
Oil In Water ◽  
Poorly Soluble ◽  
Last Stage ◽  
Positive Effect

Process approaches and intensification technological processes are integrated parts of available devices, which have a positive effect on the parameters of the obtained products. Nanoemulsions as delivery carriers are becoming more popular and there is a real need to increase the possibilities of formulation designing and engineering. Therefore, preparations of oil-in-water nanoemulsion with encapsulated cannabidiol (CBD) as oil phase were carried out in two ways: sonication method and two-stage high-pressure homogenization. The provided analysis showed spherical morphology and much larger sizes and polydispersity of nanoemulsions obtained by the sonication approach. The size of nanodroplets was from 216 nm up to 1418 nm for sonication, whereas for homogenization 128–880 nm. Additionally, it was observed that a proportionally higher percentage of surfactin resulted in a higher value of the Zeta potential. The formulations were found to be stable for at least 30 days. The in vitro experiments performed on human skin cell lines (HaCaT keratinocytes and normal dermal NHDF fibroblasts), and in vivo topical tests on probants established the biocompatibility of nanoemulsions with CBD. The last stage exhibits reduced discoloration and a higher degree of hydration by the selected systems with CBD and, thus indicating this nanoformulation as useful in cosmetics applications.

scholarly journals Berberine-Coated Biomimetic Composite Microspheres for Simultaneously Hemostatic and Antibacterial Performance

Polymers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 360
Author(s):  
Xiaojian Zhang ◽  
Kaili Dai ◽  
Chenyu Liu ◽  
Haofeng Hu ◽  
Fulin Luo ◽  
...  
Keyword(s):  
In Vitro Test ◽  
Water Emulsion ◽  
Biomedical Material ◽  
Composite Microspheres ◽  
Antibacterial Performance ◽  
New Strategy ◽  
Oil In Water Emulsion ◽  
Hemostatic Powder

Biomimetic microspheres containing alginate/carboxymethylcellulose/gelatin and coated with 0%, 1%, 3%, and 6% berberine (BACG, BACG-1B, BACG-3B, BACG-6B) were prepared by the oil-in-water emulsion method combined with spray drying. Through a series of physicochemical parameters and determination of hemostatic properties in vitro and in vivo, the results indicated that BACG and BACG-Bs were effective in inducing platelet adhesion/aggregation and promoting the hemostatic potential due to their biomimetic structure and rough surface. In addition, BACG-6B with high berberine proportion presented better hemostatic performance compared with the commercial hemostatic agent compound microporous polysaccharide hemostatic powder (CMPHP). BACG-6B also showed strong antibacterial activity in the in vitro test. The hemolysis test and cytotoxicity evaluation further revealed that the novel composite biomaterials have good hemocompatibility and biocompatibility. Thus, BACG-6B provides a new strategy for developing a due-functional (hemostat/antibacterial) biomedical material, which may have broad and promising applications in the future.

scholarly journals Peyer's Patch Dendritic Cells Process Viral Antigen from Apoptotic Epithelial Cells in the Intestine of Reovirus-infected Mice

2004 ◽  
Vol 200 (2) ◽  
pp. 235-245 ◽  
Author(s):  
Marina N. Fleeton ◽  
Nikhat Contractor ◽  
Francisco Leon ◽  
J. Denise Wetzel ◽  
Terence S. Dermody ◽  
...  
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Cd4 T Cells ◽  
Cell Protein ◽  
Peyer’S Patch ◽  
Peyer's Patch ◽  
Antigen Uptake ◽  
Cross Presentation

We explored the role of Peyer's patch (PP) dendritic cell (DC) populations in the induction of immune responses to reovirus strain type 1 Lang (T1L). Immunofluorescence staining revealed the presence of T1L structural (σ1) and nonstructural (σNS) proteins in PPs of T1L-infected mice. Cells in the follicle-associated epithelium contained both σ1 and σNS, indicating productive viral replication. In contrast, σ1, but not σNS, was detected in the subepithelial dome (SED) in association with CD11c+/CD8α−/CD11blo DCs, suggesting antigen uptake by these DCs in the absence of infection. Consistent with this possibility, PP DCs purified from infected mice contained σ1, but not σNS, and PP DCs from uninfected mice could not be productively infected in vitro. Furthermore, σ1 protein in the SED was associated with fragmented DNA by terminal deoxy-UTP nick-end labeling staining, activated caspase-3, and the epithelial cell protein cytokeratin, suggesting that DCs capture T1L antigen from infected apoptotic epithelial cells. Finally, PP DCs from infected mice activated T1L-primed CD4+ T cells in vitro. These studies show that CD8α−/CD11blo DCs in the PP SED process T1L antigen from infected apoptotic epithelial cells for presentation to CD4+ T cells, and therefore demonstrate the cross-presentation of virally infected cells by DCs in vivo during a natural viral infection.

scholarly journals Critical role of integrin CD11c in splenic dendritic cell capture of missing-self CD47 cells to induce adaptive immunity

2018 ◽  
Vol 115 (26) ◽  
pp. 6786-6791 ◽  
Author(s):  
Jiaxi Wu ◽  
Huaizhu Wu ◽  
Jinping An ◽  
Christie M. Ballantyne ◽  
Jason G. Cyster
Keyword(s):  
Critical Role ◽  
T Cell Proliferation ◽  
Cell Capture ◽  
Antigen Uptake ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Missing Self

CD11c, also known as integrin alpha X, is the most widely used defining marker for dendritic cells (DCs). CD11c can bind complement iC3b and mediate phagocytosis in vitro, for which it is also referred to as complement receptor 4. However, the functions of this prominent marker protein in DCs, especially in vivo, remain poorly defined. Here, in the process of studying DC activation and immune responses induced by cells lacking self-CD47, we found that DC capture of CD47-deficient cells and DC activation was dependent on the integrin-signaling adaptor Talin1. Specifically, CD11c and its partner Itgb2 were required for DC capture of CD47-deficient cells. CD11b was not necessary for this process but could partially compensate in the absence of CD11c. Mice with DCs lacking Talin1, Itgb2, or CD11c were defective in supporting T-cell proliferation and differentiation induced by CD47-deficient cell associated antigen. These findings establish a critical role for CD11c in DC antigen uptake and activation in vivo. They may also contribute to understanding the functional mechanism of CD47-blockade therapies.

scholarly journals Impact of the Different Preparation Methods to Obtain Autologous Non-Activated Platelet-Rich Plasma (A-PRP) and Activated Platelet-Rich Plasma (AA-PRP) in Plastic Surgery: Wound Healing and Hair Regrowth Evaluation

2020 ◽  
Vol 21 (2) ◽  
pp. 431 ◽  
Author(s):  
Pietro Gentile ◽  
Claudio Calabrese ◽  
Barbara De Angelis ◽  
Laura Dionisi ◽  
Jacopo Pizzicannella ◽  
...  
Keyword(s):  
Platelet Rich Plasma ◽  
Quality Criteria ◽  
Preparation Technique ◽  
Quality And Safety ◽  
Preparation Methods ◽  
Closed Technique ◽  
Sterile Processing

Autologous therapies using platelet-rich plasma (PRP) need meticulous preparation—currently, no standardised preparation technique exists. Processing Quantitative Standards (PQSs) define manufacturing quantitative variables (such as time, volume and pressure). Processing Qualitative Standards (PQLSs) define the quality of the materials and methods of manufacturing. The aim of this review is to use existing PQSs and PQLs to report the in vivo/in vitro results obtained by using different Kits, that utilise different procedures (classified as Closed-Technique and Opened-Technique) to isolate autologous human activated (AA-PRP) or non-activated PRP (A-PRP). PQSs included the volumes of blood collected as well as the reagents used, the time/gravity of centrifugation, and the duration, temperature and tilt level/speed of centrifugation. PQLSs included the use of Calcium Chloride CaCl2, Kit weight, transparency of Kit components, the maintenance of a closed sterile processing environment and the use of a small centrifuge. Eight CE marked devices for PRP extraction were evaluated: Angel®, Biomed®, Cascade® and Selphyl®, Mag-18®, i-Stem®, MyCells® and Regenlab®. Using a Kit with the PQSs and PQLSs described in this study enables the isolation of A-PRP, thereby meeting consensus quality criteria. As our understanding of Critical Quality Attributes (CQAs) of A-PRP continues to evolve, especially with respect to purity and potency, adjustments to these benchmark PQSs and PQLs will hopefully help isolate A-PRP of desired CQAs with greater reproducibility, quality, and safety. Confirmatory studies will no doubt need to be completed.

scholarly journals Trypanosomatid-Caused Conditions: State of the Art of Therapeutics and Potential Applications of Lipid-Based Nanocarriers

2020 ◽  
Vol 8 ◽  
Author(s):  
Giuliana Muraca ◽  
Ignacio Rivero Berti ◽  
María L. Sbaraglini ◽  
Wagner J. Fávaro ◽  
Nelson Durán ◽  
...  
Keyword(s):  
Chagas Disease ◽  
State Of The Art ◽  
Therapeutic Interventions ◽  
Safety Issues ◽  
Routes Of Administration ◽  
Treatment Regimens ◽  
Lipid Nanocarriers ◽  
Approved Drugs

Trypanosomatid-caused conditions (African trypanosomiasis, Chagas disease, and leishmaniasis) are neglected tropical infectious diseases that mainly affect socioeconomically vulnerable populations. The available therapeutics display substantial limitations, among them limited efficacy, safety issues, drug resistance, and, in some cases, inconvenient routes of administration, which made the scenarios with insufficient health infrastructure settings inconvenient. Pharmaceutical nanocarriers may provide solutions to some of these obstacles, improving the efficacy–safety balance and tolerability to therapeutic interventions. Here, we overview the state of the art of therapeutics for trypanosomatid-caused diseases (including approved drugs and drugs undergoing clinical trials) and the literature on nanolipid pharmaceutical carriers encapsulating approved and non-approved drugs for these diseases. Numerous studies have focused on the obtention and preclinical assessment of lipid nanocarriers, particularly those addressing the two currently most challenging trypanosomatid-caused diseases, Chagas disease, and leishmaniasis. In general, in vitro and in vivo studies suggest that delivering the drugs using such type of nanocarriers could improve the efficacy–safety balance, diminishing cytotoxicity and organ toxicity, especially in leishmaniasis. This constitutes a very relevant outcome, as it opens the possibility to extended treatment regimens and improved compliance. Despite these advances, last-generation nanosystems, such as targeted nanocarriers and hybrid systems, have still not been extensively explored in the field of trypanosomatid-caused conditions and represent promising opportunities for future developments. The potential use of nanotechnology in extended, well-tolerated drug regimens is particularly interesting in the light of recent descriptions of quiescent/dormant stages of Leishmania and Trypanosoma cruzi, which have been linked to therapeutic failure.

scholarly journals Induced Pluripotent Stem Cells as Vasculature Forming Entities

2019 ◽  
Vol 8 (11) ◽  
pp. 1782 ◽  
Author(s):  
Antonio Palladino ◽  
Isabella Mavaro ◽  
Carmela Pizzoleo ◽  
Elena De Felice ◽  
Carla Lucini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Regenerative Medicine ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Tissue Growth ◽  
Safety Issues ◽  
Induced Pluripotent

Tissue engineering (TE) pursues the ambitious goal to heal damaged tissues. One of the most successful TE approaches relies on the use of scaffolds specifically designed and fabricated to promote tissue growth. During regeneration the guidance of biological events may be essential to sustain vasculature neoformation inside the engineered scaffold. In this context, one of the most effective strategies includes the incorporation of vasculature forming cells, namely endothelial cells (EC), into engineered constructs. However, the most common EC sources currently available, intended as primary cells, are affected by several limitations that make them inappropriate to personalized medicine. Human induced Pluripotent Stem Cells (hiPSC), since the time of their discovery, represent an unprecedented opportunity for regenerative medicine applications. Unfortunately, human induced Pluripotent Stem Cells-Endothelial Cells (hiPSC-ECs) still display significant safety issues. In this work, we reviewed the most effective protocols to induce pluripotency, to generate cells displaying the endothelial phenotype and to perform an efficient and safe cell selection. We also provide noteworthy examples of both in vitro and in vivo applications of hiPSC-ECs in order to highlight their ability to form functional blood vessels. In conclusion, we propose hiPSC-ECs as the preferred source of endothelial cells currently available in the field of personalized regenerative medicine.

Mapping the Decadal (2009–2018) Research Landscape of Nanotoxicity: Insights from a Bibliometric Study

2019 ◽  
Vol 11 (10) ◽  
pp. 1327-1337
Author(s):  
Xin Chen
Keyword(s):  
Rapid Development ◽  
Reproductive Toxicity ◽  
Experimental Models ◽  
Future Research ◽  
Imaging Diagnosis ◽  
Safety Issues ◽  
The Past ◽  
Institutional Impact

Nanomaterials (NMs) have wide applications in industrial and household areas, and possibilities of exposure to NMs are increasing, prompting considerable concerns about safety issues related to them. This paper describes the research landscape of nanotoxicity over the past ten years by adopting bibliometric methods. Annual, regional, and institutional distributions, as well as regional/institutional impact of literature on nanotoxicity were analyzed. Both quantitative and citation-based analyses were carried out to reveal the research hotspots. Results showed that cytotoxicity was the most concerned issue in the application of NMs, especially in imaging, diagnosis, and therapy. There were also a large number of studies on ecotoxicity, oxidative stress, apoptosis, genotoxicity, inflammation, and reproductive toxicity caused by NMs. NMs such as Ag, Au, graphene-based materials (GBMs), carbon nanotubes (CNTs), TiO2, SiO2, etc. were the most studied materials. Moreover, a growing number of both in vivo and in vitro studies involving NMs have been carried out in the past ten years. Mammalian models, such as mouse, human and rat, were the most studied models. A Sankey diagram between study types and experimental models showed that in vivo studies exceeded in vitro studies for some well-established animal models. Yet in-depth in vivo studies regarding interactions of NMs within human systems were still essential. With rapid development of nanotechnology, toxic and safety issues on NMs need to be addressed more specifically in future research.

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