scholarly journals Biocompatible Lipid Polymer Cationic Nanoparticles for Antigen Presentation

Polymers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 185
Author(s):  
Yunys Pérez-Betancourt ◽  
Bianca de Carvalho Lins Fernandes Távora ◽  
Eliana L. Faquim-Mauro ◽  
Ana Maria Carmona-Ribeiro

Biocompatible lipid polymer nanoparticles (NPs) previously used as antimicrobial agents are explored here as immuno-adjuvants. Poly (methyl methacrylate) (PMMA)/dioctadecyldimethylammonium bromide (DODAB)/poly (diallyldimethylammonium chloride) (PDDA) nanoparticles (NPs) were prepared by emulsion polymerization of methyl methacrylate (MMA) in the presence of DODAB and PDDA, with azobisisobutyronitrile (AIBN) as the initiator. NPs characterization after dialysis by dynamic light-scattering yielded 225 ± 2 nm hydrodynamic diameter (Dz), 73 ± 1 mV zeta-potential (ζ), and 0.10 ± 0.01 polydispersity (P). Ovalbumin (OVA) adsorption reduced ζ to 45 ± 2 mV. Balb/c mice immunized with NPs/OVA produced enhanced OVA-specific IgG1 and IgG2a, exhibited moderate delayed type hypersensitivity reaction, and enhanced cytokines production (IL-4, IL-10, IL-2, IFN-γ) by cultured spleen cells. There was no cytotoxicity against cultured macrophages and fibroblasts. Advantages of the PMMA/DODAB/PDDA NPs were high biocompatibility, zeta-potential, colloidal stability, and antigen adsorption. Both humoral and cellular antigen-specific immune responses were obtained.

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 105 ◽  
Author(s):  
Yunys Pérez-Betancourt ◽  
Bianca de Carvalho Lins Fernandes Távora ◽  
Mônica Colombini ◽  
Eliana L. Faquim-Mauro ◽  
Ana Maria Carmona-Ribeiro

Since antigens are negatively charged, they combine well with positively charged adjuvants. Here, ovalbumin (OVA) (0.1 mg·mL−1) and poly (diallyldimethylammonium chloride) (PDDA) (0.01 mg·mL−1) yielded PDDA/OVA assemblies characterized by dynamic light scattering (DLS) and scanning electron microscopy (SEM) as spherical nanoparticles (NPs) of 170 ± 4 nm hydrodynamic diameter, 30 ± 2 mV of zeta-potential and 0.11 ± 0.01 of polydispersity. Mice immunization with the NPs elicited high OVA-specific IgG1 and low OVA-specific IgG2a production, indicating a Th-2 response. Delayed-type hypersensitivity reaction (DTH) was low and comparable to the one elicited by Al(OH)3/OVA, suggesting again a Th-2 response. PDDA advantages as an adjuvant were simplicity (a single-component adjuvant), low concentration needed (0.01 mg·mL−1 PDDA) combined with antigen yielding neglectable cytotoxicity, and high stability of PDDA/OVA dispersions. The NPs elicited much higher OVA-specific antibodies production than Al(OH)3/OVA. In vivo, the nano-metric size possibly assured antigen presentation by antigen-presenting cells (APC) at the lymph nodes, in contrast to the location of Al(OH)3/OVA microparticles at the site of injection for longer periods with stimulation of local dendritic cells. In the future, it will be interesting to evaluate combinations of the antigen with NPs carrying both PDDA and elicitors of the Th-1 response.


2021 ◽  
Vol 16 ◽  
pp. 165-171
Author(s):  
V. V. Rodchenko ◽  
Kyaw Ye Ko

In this work, the preparation of Fe3O4 nanoparticles modified with 3-aminopropyltriethoxysilane (APTES) was carried out under various synthesis modes (in air or in argon). The zeta potential and hydrodynamic diameter of Fe3O4-APTES nanoparticles were determined by the method of dynamic and electrokinetic light scattering. The effect of humic acids on the zeta potential, hydrodynamic diameter and colloidal stability of Fe3O4-APTES at different pH values was established by the method of dynamic and electrophoretic light scattering. It has been shown that changes in the conditions of the synthesis of nanoparticles of one component composition Fe3O4-APTES (argon) and Fe3O4-APTES (air) (in an inert medium and in an air atmosphere, respectively) lead to a change in the charge of the particle surface and a subsequent change in the sorption properties with respect to HA. It was demonstrated that the decisive role in the study of surface properties is played by the purification from low-molecular-weight impurities that can screen the surface of nanoparticles or bind with an indifferent electrolyte. The stage of dispersive post-preparation of samples is also important for the correct determination of the sorption capacity and hydrodynamic diameter of particles.


Materials ◽  
2021 ◽  
Vol 14 (11) ◽  
pp. 2736
Author(s):  
Zuiliang Deng ◽  
Guimin Lu ◽  
Lefeng Fu ◽  
Weishan Wang ◽  
Baicun Zheng

The aim of this paper is to study the adsorption behavior of polycarboxylate superplasticizers (PCE) on coarse aggregates with a property of high water consumption (above 2%). The coarse aggregates were ground into a powder to create large bibulous stone powder, and it was observed that significant amounts of the ether-based PCE were absorbed onto large bibulous stone powder. The adsorption rate immediately reached a maximum after 5 min and then gradually decreased until an equilibrium absorption was established after 30 min. Zeta potential, infrared spectroscopy, and thermogravimetric analysis (TGA) measurements confirmed that the polycarboxylate superplasticizer adsorbed on the surface of the stone powder. Hydrodynamic diameter measurements showed that the polycarboxylate superplasticizer molecules were smaller than pore size, and the surface area and pore volume were reduced by the polymer incorporation in the pores.


Materials ◽  
2021 ◽  
Vol 14 (2) ◽  
pp. 290
Author(s):  
Yannic Ramaye ◽  
Marta Dabrio ◽  
Gert Roebben ◽  
Vikram Kestens

Zeta potential is frequently used to examine the colloidal stability of particles and macromolecules in liquids. Recently, it has been suggested that zeta potential can also play an important role for grouping and read-across of nanoforms in a regulatory context. Although the measurement of zeta potential is well established, only little information is reported on key metrological principles such as validation and measurement uncertainties. This contribution presents the results of an in-house validation of the commonly used electrophoretic light scattering (ELS) and the relatively new particle tracking analysis (PTA) methods. The performance characteristics were assessed by analyzing silica and polystyrene reference materials. The ELS and PTA methods are robust and have particle mass working ranges of 0.003 mg/kg to 30 g/kg and 0.03 mg/kg to 1.5 mg/kg, respectively. Despite different measurement principles, both methods exhibit similar uncertainties for repeatability (2%), intermediate precision (3%) and trueness (4%). These results confirm that the developed methods can accurately measure the zeta potential of silica and polystyrene particles and can be transferred to other laboratories that analyze similar types of samples. If direct implementation is impossible, the elaborated methodologies may serve as a guide to help laboratories validating their own methods.


2021 ◽  
Vol 901 ◽  
pp. 117-122
Author(s):  
Netnapa Ontao ◽  
Sirivan Athikomkulchai ◽  
Sarin Tadtong ◽  
Phuriwat Leesawat ◽  
Chuda Chittasupho

Ocimum gratissimum L. leaf oil exhibited many pharmacological properties. This study aimed to formulate and evaluate the physical and chemical stability of O.gratissimum leaf oil nanoemulsion. O.gratissimum leaf oil was extracted by hydrodistillation. The major component of the essential oil eugenol, was analyzed by UV-Vis spectrophotometry. Nanoemulsions of O.gratissimum leaf oil were formulated using polysorbate 80, hyaluronic acid, poloxamer 188, and deionized water by phase inversion composition method. The hydrodynamic diameter, polydispersity index, and zeta potential value of O.gratissimum leaf oil nanoemulsion was evaluated by a dynamic light scattering technique. The %remaining of eugenol in the nanoemulsion was analyzed by UV-Vis spectrophotometry. The essential oil extracted from of O. gratissimum leaf oil was a clear, pale yellow color. The %yield of the essential oil was 0.15 ± 0.03% v/w. The size of the nanoemulsion was less than 106 nm. The polydispersity index of the nanoemulsion was ranging from 0.303 - 0.586 and the zeta potential value of the nanoemulsion was closely to zero, depending on the formulation component. O. gratissimum leaf oil at concentrations ranging from 0.002 - 0.012% v/v contained 35 - 41% of eugenol. The size of nanoemulsion was significantly decreased after storage at 4 °C, while significantly increased upon storage at 45 °C. The size of nanoemulsion stored at 30 °C did not significantly change. The %remaining of eugenol in the nanoemulsion was more than 90% after storage at 4 °C and 30 °C for 28 days. The percentage of eugenol remaining in the nanoemulsion stored at 45 °C was more than 85 - 90%, suggesting that the temperature affected the stability of eugenol in the nanoemulsion.


1980 ◽  
Vol 29 (2) ◽  
pp. 633-641 ◽  
Author(s):  
Thuang S. Lim ◽  
Juneann W. Murphy ◽  
Larry K. Cauley

Inbred CBA/J mice were used in developing a defined in vivo model for studying host-parasite relationships in cryptococcosis. Mice were infected either intranasally or intraperitoneally with 10 3 viable Cryptococcus neoformans cells. At weekly intervals over a 92-day period, C. neoformans growth profiles in the lungs, spleens, livers, and brains of the infected animals were determined. In addition, humoral and delayed-type hypersensitivity responses and cryptococcal antigen levels were assayed in these mice. Intranasally infected mice developed strong delayed-type hypersensitivity reactions in response to cryptococcal culture filtrate (CneF) antigen, and there was good correlation between acquisition of delayed-type hypersensitivity and the reduction of C. neoformans cell numbers in infected tissues. In contrast, intraperitoneally infected mice displayed greater numbers of C. neoformans cells in tissues and had somewhat suppressed delayed-type hypersensitivity responses to CneF antigen. Anticryptococcal antibodies were not detected in intranasally or intraperitoneally infected mice, but cryptococcal polysaccharide antigen titers were relatively high in both groups. The transfer of sensitized spleen cells from intranasally infected mice to syngeneic naive recipient mice resulted in the transfer of delayed-type hypersensitivity responsiveness to cryptococcal antigen in the recipients. The intranasally induced infection in mice was similar to the naturally acquired infection in humans; therefore we are proposing that this murine-cryptococcosis model would be useful in gaining a greater understanding of host-etiological agent relationships in this disease.


1998 ◽  
Vol 188 (6) ◽  
pp. 1191-1196 ◽  
Author(s):  
Mark H. Kaplan ◽  
Andrea L. Wurster ◽  
Michael J. Grusby

The differentiation of T helper (Th) cells is regulated by members of the signal transducer and activator of transcription (STAT) family of signaling molecules. We have generated mice lacking both Stat4 and Stat6 to examine the ability of Th cells to develop in the absence of these two transcription factors. Stat4, Stat6−/− lymphocytes fail to differentiate into interleukin (IL)-4–secreting Th2 cells. However, in contrast to Stat4−/− lymphocytes, T cells from Stat4, Stat6−/− mice produce significant amounts of interferon (IFN)-γ when activated in vitro. Although Stat4, Stat6−/− lymphocytes produce less IFN-γ than IL-12–stimulated control lymphocytes, equivalent numbers of IFN-γ–secreting cells can be generated from cultures of Stat4, Stat6−/− lymphocytes activated under neutral conditions and control lymphocytes activated under Th1 cell–promoting conditions. Moreover, Stat4, Stat6−/− mice are able to mount an in vivo Th1 cell–mediated delayed-type hypersensitivity response. These results support a model of Th cell differentiation in which the generation of Th2 cells requires Stat6, whereas a Stat4-independent pathway exists for the development of Th1 cells.


1995 ◽  
Vol 83 (6) ◽  
pp. 1038-1044 ◽  
Author(s):  
Terry Lichtor ◽  
Roberta P. Glick ◽  
Tae Sung Kim ◽  
Roger Hand ◽  
Edward P. Cohen

✓ A novel approach toward the treatment of glioma was developed in a murine model. The genes for both interleukin-2 (IL-2) and interferon-γ (IFN-γ) were first transfected into a mouse fibroblast cell line that expresses defined major histocompatibility complex (MHC) determinants (H—2k). The double cytokine—secreting cells were then cotransplanted intracerebrally with the Gl261 murine glioma cell line into syngeneic C57BL/6 mice (H—2b) whose cells differed at the MHC from the cellular immunogen. The results indicate that the survival of mice with glioma injected with the cytokine-secreting allogeneic cells was significantly prolonged, relative to the survival of mice receiving equivalent numbers of glioma cells alone. Using a standard 51Cr-release assay, the specific release of isotope from labeled Gl261 cells coincubated with spleen cells from mice injected intracerebrally with the glioma cells and the cytokine-secreting fibroblasts was significantly higher than the release of isotope from glioma cells coincubated with spleen cells from nonimmunized mice. The cellular antiglioma response was mediated by natural killer/lymphokine-activated killer and Lyt-2.2+ (CD8+) cells. The increased survival of mice with glioma and the specific immunocytotoxic responses after immunization with fibroblasts modified to secrete both IL-2 and IFN-γ indicate the potential of an immunotherapeutic approach to gliomas with cytokine-secreting cells.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Adriana Bezerra-Souza ◽  
Jéssica A. de Jesus ◽  
Márcia D. Laurenti ◽  
Aikaterini Lalatsa ◽  
Dolores R. Serrano ◽  
...  

The production of ergosterol lipid involves the activity of different enzymes and is a crucial event for the Leishmania membrane homeostasis. Such enzymes can be blocked by azoles and allylamines drugs, such as the antifungal butenafine chloride. This drug was active on parasites that cause cutaneous and visceral leishmaniasis. Based on the leishmanicidal activity of butenafine chloride and considering the absence of reports about the therapeutic potential of this drug in cutaneous leishmaniasis, the present work is aimed at analyzing the efficacy of butenafine formulated in two different topical delivery systems, the self-nanoemulsifying drug delivery systems (BUT-SNEDDS) and in a SNEDDS-based nanogel (BUT-SNEDDS gel) as well as in the free form in experimental cutaneous leishmaniasis. Physical studies showed that both formulations were below 300 nm with low polydispersity (<0.5) good colloidal stability (around -25 mV). Increased steady-state flux was reported for nanoenabled butenafine formulations with reduced lag time in Franz cell diffusion assays across Strat-M membranes. No toxic or inflammatory reactions were detected in animals treated with BUT-SNEDDS, BUT-SNEDDS gel, or butenafine. Animals topically treated with butenafine (free or nanoformulated) showed small dermal lesions and low tissue parasitism. Furthermore, BUT-SNEDD gel and butenafine presented similar efficacy than the standard drug Glucantime given by the intralesional route. Increased levels of IFN-γ were observed in animals treated with BUT-SNEDDS gel or butenafine. Based on these data, the antifungal drug butenafine chloride can be considered an interesting repurposed drug for the treatment of cutaneous leishmaniasis.


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