Maltodextrin Nanoparticles Research Articles

Intranasal versus intradermal immunoprotective effect of maltodextrin nanoparticles loaded with SAG1 against toxoplasmosis on murine model

Intranasal versus intradermal immunoprotective effect of maltodextrin nanoparticles loaded with SAG1 against toxoplasmosis on murine model

Spiramycin-loaded maltodextrin nanoparticles as a promising treatment of toxoplasmosis on murine model

Despite being the initial choice for treating toxoplasmosis, sulfadiazine and pyrimethamine have limited effectiveness in eliminating the infection and were linked to a variety of adverse effects. Therefore, the search for new effective therapeutic strategies against toxoplasmosis is still required. The current work is the first research to assess the efficacy of spiramycin-loaded maltodextrin nanoparticles (SPM-loaded MNPs) as a novel alternative drug therapy against toxoplasmosis in a murine model. Fifty laboratory-bred Swiss albino mice were divided into five groups: normal control group (GI, n = 10), positive control group (GII, n = 10), orally treated with spiramycin (SPM) alone (GIII, n = 10), intranasal treated with SPM-loaded MNPs (GIV, n = 10), and orally treated with SPM-loaded MNPs (GV, n = 10). Cysts of Toxoplasma gondii ME-49 strain were used to infect the mice. Tested drugs were administered 2 months after the infection. Drug efficacy was assessed by counting brain cysts, histopathological examination, and measures of serum CD19 by flow cytometer. The orally treated group with SPM-loaded MNPs (GV) showed a marked reduction of brain cyst count (88.7%), histopathological improvement changes, and an increasing mean level of CD19 (80.2%) with significant differences. SPM-loaded MNPs showed potent therapeutic effects against chronic toxoplasmosis. Further research should be conducted to assess it in the treatment of human toxoplasmosis, especially during pregnancy.Graphical

Human T-cell activation withToxoplasma gondiiantigens loaded in maltodextrin nanoparticles

Toxoplasmosis is the most prevalent parasitic zoonosis worldwide, causing ocular and neurological diseases. No vaccine has been approved for human use. We evaluated the response of peripheral blood mononuclear cells (PBMCs) to a novel construct ofToxoplasma gondiitotal antigen in maltodextrin nanoparticles (NP/TE) in individuals with varying infectious statuses (uninfected, chronic asymptomatic, or ocular toxoplasmosis). We analyzed the concentration of IFN-γ after NP/TE ex vivo stimulation using ELISA and the immunophenotypes of CD4+and CD8+cell populations using flow cytometry. In addition, serotyping of individuals with toxoplasmosis was performed by ELISA using GRA6-derived polypeptides. Low doses of NP/TE stimulation (0.9 μg NP/0.3 μg TE) achieved IFN-γ–specific production in previously exposed human PBMCs without significant differences in the infecting serotype. Increased IFN-γ expression in CD4+effector memory cell subsets was found in patients with ocular toxoplasmosis with NP/TE but not with TE alone. This is the first study to show how T-cell subsets respond to ex vivo stimulation with a vaccine candidate for human toxoplasmosis, providing crucial insights for future clinical trials.

Optimized extraction and nanoencapsulation of artemisia essential oils: A comprehensive analysis of bioactives and structural characterization

This study pertains to essential oil extraction from Artemisia absinthium L and a comparison of multiple extraction techniques. Ultrasound-assisted extraction emerged as the superior method, demonstrating remarkable extract recovery in contrast to microwave and hydrodistillation approaches. Bioactive compounds within the extracted Artemisia essential oils were meticulously identified through Gas Chromatography-Mass Spectrometry (GCMS), shedding light on the chemical composition. Furthermore, we employed maltodextrin nanoparticles as a sophisticated nanocarrier for encapsulating the extracted oil. Our investigation encompassed various maltodextrin-to-artemisia extract ratios (1:10, 1:20, and 1:30), revealing encapsulation efficiencies of 75.21%, 78.23%, and 85.24%, respectively. Characterization of the nanoencapsulated powders through scanning electron microscopy unveiled their distinctive irregular morphology. X-ray diffraction (XRD), full width at half maximum for artemisia extract powder and nanoencapsulated powder were 0.12, 8.2, 8.70, and 8.89 and Fourier-transform infrared (FTIR), typical bands were 1348, 1625, 1596, 1614, 2920 cm−1. XRD and FTIR analyses furnished compelling evidence of successful encapsulation, presenting the artemisia extract in an amorphous state. Notably, the XRD patterns indicated a low degree of crystallinity, affirming the innovative nature of our approach. Significantly, the encapsulated powders retained the characteristic absorption bands of the artemisia extract, underscoring the preservation of its essential chemical properties throughout the encapsulation process.

Maltodextrin-Nanoparticles as a Delivery System for Nasal Vaccines: A Review Article.

Nanoparticles are increasingly being studied as antigen delivery systems for immunization with nasal vaccines. The addition of adjuvants is still generally required in many nanoparticle formulations, which can induce potential side effects owing to mucosal reactogenicity. In contrast, maltodextrin nanoparticles do not require additional immunomodulators, and have been shown to be efficient vaccine delivery systems. In this review, the development of maltodextrin nanoparticles is presented, specifically their physico-chemical properties, their ability to load antigens and deliver them into airway mucosal cells, and the extent to which they trigger protective immune responses against bacterial, viral, and parasitic infections. We demonstrate that the addition of lipids to maltodextrin nanoparticles increases their potency as a vaccine delivery system for nasal administration.

Nasal vaccination of six squirrel monkeys (Saimiri sciureus): Improved immunization protocol against Toxoplasma gondii with a nanoparticle-born vaccine

Toxoplasma gondii is an intracellular protozoon found worldwide, which completes its life cycle between felids (its definitive host) and other warm-blooded animals. While the infection rarely leads to severe complications in humans, many animal species are very susceptible to this infection, for example the squirrel monkey (Saimiri sciureus) which is the subject of this study. Toxoplasmosis is lethal for 80% of cases in this species, and fatal outbreaks are frequently reported in zoological parks.No efficient treatment exists, but a new vaccine prepared with maltodextrin nanoparticles containing killed T. gondii antigens has been tested recently in French zoos. The animals were immunized through heterologous administrations, with two nasal doses at one-month interval, followed by nasal/subcutaneous boosts thereafter. No death has been reported since the beginning of this vaccination campaign, but we felt the protocol could be simplified.Here, an improved and less-invasive immunization protocol was evaluated on 6 Saimiri sciureus in the French zoo La Palmyre. It consisted of two nasal administrations at one-month interval, followed by a nasal boost at 6 months. A specific memory T-cell immunity was observed by ELISPOT after two administrations in all the animals, without humoral responses. The results suggest that 2 nasal administrations induce a protective immune response against T. gondii infection and might be sufficient to induce a strong Tcell memory, further improving immunity.

Dipalmitoyl-phosphatidylserine-filled cationic maltodextrin nanoparticles exhibit enhanced efficacy for cell entry and intracellular protein delivery in phagocytic THP-1 cells.

Vaccination through the upper respiratory tract is a promising strategy, and particulate antigens, such as antigens associated with nanoparticles, triggered a stronger immune response than the sole antigens. Cationic maltodextrin-based nanoparticles loaded with phosphatidylglycerol (NPPG) are efficient for intranasal vaccination but non-specific to trigger immune cells. Here we focused on phosphatidylserine (PS) receptors, specifically expressed by immune cells including macrophages, to improve nanoparticle targeting through an efferocytosis-like mechanism. Consequently, the lipids associated with NPPG have been substituted by PS to generate cationic maltodextrin-based nanoparticles with dipalmitoyl-phosphatidylserine (NPPS). Both NPPS and NPPG exhibited similar physical characteristics and intracellular distribution in THP-1 macrophages. NPPS cell entry was faster and higher (two times more) than NPPG. Surprisingly, competition of PS receptors with phospho-L-serine did not alter NPPS cell entry and annexin V did not preferentially interact with NPPS. Although the protein association is similar, NPPS delivered more proteins than NPPG in cells. On the contrary, the proportion of mobile nanoparticles (50%), the movement speed of nanoparticles (3 µm/5 min), and protein degradation kinetics in THP-1 were not affected by lipid substitution. Together, the results indicate that NPPS enter cells and deliver protein better than NPPG, suggesting that modification of the lipids of cationic maltodextrin-based nanoparticles may be a useful strategy to enhance nanoparticle efficacy for mucosal vaccination.

Effective immuno-therapeutic treatment of Canine Leishmaniasis.

Canine Leishmaniasis (CanL) caused by the L. infantum species is one of the biggest threats to the health of the South American canine population. Chemotherapeutics currently used for the treatment of CanL fail to induce a total parasite clearance while inducing numerous side effects. As CanL is an immunomodulated disease, the use of immuno-treatments should strengthen the deficient immune response of infected dogs. In this study, we evaluated a nasally administered immunotherapy in dogs naturally infected with L. infantum (stage 2), with both visceral and cutaneous manifestations. Noteworthy, some of them were also infected by other parasites (E. canis, D. immitis, A. platys), what worsen their chance of survival. The treatment was based on 2 intranasal (IN.) administrations of a killed L. infantum parasite loaded into maltodextrin nanoparticles, which treatment was compared with the classical oral administration of Miltefosine (2 mg/kg) for 28 days, as well as a combination of these 2 treatments. The results showed that two IN administrations significantly reduced the serology, and were at least as efficient as the chemotherapy to reduce the skin and bone marrow parasite burden, as well as clinical scores, and that unlike Miltefosine treatments, this nasally administered nanoparticle vaccine was without side effects. These results confirm the feasibility of a simple therapeutic immuno-treatment against L. infantum infected dogs, which is a promising tool for future developments.

Formulation attributes, acid tunable degradability and cellular interaction of acetalated maltodextrin nanoparticles

Exploiting materials for nanoparticle production has never halted to address the diversity in cargos and applications. Herein, maltodextrin (MD) was selected for being economic, nontoxic, biocompatible, and biodegradable. Different MDs were modified through acetal modification, turning the polymer hydrophobic and allowing pH-dependent tunable degradability. The synthesized acetalated MD (AcMD) polymers exhibited different thermal decomposition profiles and lower glass transition temperatures. Nanoprecipitation yielded uniform AcMD nanoparticles (NPs) with diameters ranging from 141 to 258 nm. The particles were loaded with hydrophobic model drug, resveratrol (67.86% entrapment efficiency and 3.75% drug loading). The degradation and the in vitro release were studied at pH 7.4 and pH 5.0 and revealed different kinetics in dependence on the amount of cyclic/acyclic acetalation. Cell viability and cellular interaction were studied on adenocarcinoma human lung epithelial A549 and differentiated human monocytic THP-1 cells. The AcMD-NPs were well tolerated by both cell lines but exhibited different uptake behaviors.

Effective Nanoparticle-Based Nasal Vaccine Against Latent and Congenital Toxoplasmosis in Sheep.

Toxoplasma gondii is a parasitic protozoan of worldwide distribution, able to infect all warm-blooded animals, but particularly sheep. Primary infection in pregnant sheep leads to millions of abortions and significant economic losses for the livestock industry. Moreover, infected animals constitute the main parasitic reservoir for humans. Therefore, the development of a One-health vaccine seems the best prevention strategy. Following earlier work, a vaccine constituted of total extract of Toxoplasma gondii proteins (TE) associated with maltodextrin nanoparticles (DGNP) was developed in rodents. In this study we evaluated the ability of this vaccine candidate to protect against latent and congenital toxoplasmosis in sheep. After two immunizations by either intranasal or intradermal route, DGNP/TE vaccine generated specific Th1-cellular immune response, mediated by APC-secretion of IFN-γ and IL-12. Secretion of IL-10 appeared to regulate this Th1 response for intradermally vaccinated sheep but was absent in intranasally-vaccinated animals. Finally, protection against latent toxoplasmosis and transplacental transmission were explored. Intranasal vaccination led to a marked decrease of brain cysts compared with the non-vaccinated group. This DGNP/TE vaccine administered intranasally conferred a high level of protection against latent toxoplasmosis and its transplacental transmission in sheep, highlighting the potential for development of such a vaccine for studies in other species.

Importance of the Phospholipid Core for Mucin Hydrogel Penetration and Mucosal Cell Uptake of Maltodextrin Nanoparticles.

Nanoparticles (NPs) used as mucosal antigen delivery systems are a promising way to vaccinate. However, NPs have to cross the mucus gel and penetrate into mucosal cells to deliver antigens, and a mismatch exists between mucopenetrating NPs, rarely able to interact with cells, and NPs designed to deliver antigens into cells, but often described as mucoadhesives. Here, we compared the ability of cationic maltodextrin-based NPs, either without (NP+) or with an anionic phospholipid core (NPL), to interact with mucins and airway epithelial cells. We showed that their lipid core increased the NPL's mobility in mucin hydrogel by reducing interactions with mucins. Similarly, the uptake and protein delivery by NPLs into airway epithelial cells were not hindered by mucins. This highlights the importance of anionic lipids in the NPL, which are more efficient in crossing the mucin hydrogel while retaining the ability to interact with epithelial cells, an intermediate behavior between mucoadhesive and mucopenetrating NPs.

Preparation of maltodextrin nanoparticles and encapsulation of bovine serum albumin – Influence of formulation parameters

Maltodextrin, which is obtained by partial hydrolysis of starch, is water soluble and could serve as hydrophilic carrier for the encapsulation of protein-based active pharmaceutical ingredients. We investigated three different commercial maltodextrins (Dextrose Equivalents (DE) 4.0–7.0, DE 13.0–17.0 and DE 16.5–19.5) with focus on their ability to form nanoparticles by inverse precipitation.Successful particle formation was observed for DE 13.0–17.0 and DE 16.5–19.5 but not for DE 4.0–7.0. The process was investigated using acetone as anti-solvent and poloxamer 407 as stabilizer. A tunable size between 170 nm and 450 nm was achieved by varying the type of maltodextrin and the stabilizer concentration. Particles were spherical in shape and were stable over a time period of 14 days. Maltodextrin nanoparticles (MD NPs) were tested on A549 cells and did not show any cytotoxic effects. This underlines the potential of maltodextrin as material for drug delivery systems. Bovine serum albumin (BSA) as a model protein was successfully encapsulated into MD NPs with encapsulation efficiencies of approx. 70% and loading rates of up to 20%.

Stimulus-activatable echogenic maltodextrin nanoparticles as nanotheranostic agents for peripheral arterial disease

Reactive oxygen species (ROS) are closely related with various pathological disorders. Therefore, real-time detection of ROS is essential for understanding the procedure of diseases and diagnosing the accurate lesion sites. Hydrogen peroxide (H2O2) accounts for a large portion of ROS and has a longer half-life than other ROS, which makes it a highly promising diagnostic and therapeutic biomarker. In this work, we developed H2O2-activatable CO2 bubble generating indocyanine green-loaded boronated maltodextrin (ICG-BM) nanoparticles for imaging and therapy of peripheral arterial disease. ICG-BM nanoparticles displayed increasing fluorescence, ultrasound and photoacoustic signals in H2O2-triggered manners and exerted significant anti-inflammatory and proangiogenic effects in H2O2-stimulated vascular endothelial cells. In mouse models of hindlimb ischemia, ICG-BM nanoparticles also showed H2O2-triggered amplification of fluorescence, ultrasound and photoacoustic signals in the ischemic hindlimb muscles. ICG-BM nanoparticles also significantly reduced the level of overproduced H2O2 and exerted highly potent anti-inflammatory and proangiogenic activities in the ischemic tissues. We therefore believe that pathological stimulus-activatable echogenic ICG-BM nanoparticles provide a new avenue for imaging and treatment of peripheral arterial disease.

Porous Nanoparticles With Self-Adjuvanting M2e-Fusion Protein and Recombinant Hemagglutinin Provide Strong and Broadly Protective Immunity Against Influenza Virus Infections.

Due to the high risk of an outbreak of pandemic influenza, the development of a broadly protective universal influenza vaccine is highly warranted. The design of such a vaccine has attracted attention and much focus has been given to nanoparticle-based influenza vaccines which can be administered intranasally. This is particularly interesting since, contrary to injectable vaccines, mucosal vaccines elicit local IgA and lung resident T cell immunity, which have been found to correlate with stronger protection in experimental models of influenza virus infections. Also, studies in human volunteers have indicated that pre-existing CD4+ T cells correlate well to increased resistance against infection. We have previously developed a fusion protein with 3 copies of the ectodomain of matrix protein 2 (M2e), which is one of the most explored conserved influenza A virus antigens for a broadly protective vaccine known today. To improve the protective ability of the self-adjuvanting fusion protein, CTA1-3M2e-DD, we incorporated it into porous maltodextrin nanoparticles (NPLs). This proof-of-principle study demonstrates that the combined vaccine vector given intranasally enhanced immune protection against a live challenge infection and reduced the risk of virus transmission between immunized and unimmunized individuals. Most importantly, immune responses to NPLs that also contained recombinant hemagglutinin (HA) were strongly enhanced in a CTA1-enzyme dependent manner and we achieved broadly protective immunity against a lethal infection with heterosubtypic influenza virus. Immune protection was mediated by enhanced levels of lung resident CD4+ T cells as well as anti-HA and -M2e serum IgG and local IgA antibodies.

Stabilization of Human Tyrosine Hydroxylase in Maltodextrin Nanoparticles for Delivery to Neuronal Cells and Tissue.

Enzyme replacement therapy (ERT) is a therapeutic approach envisioned decades ago for the correction of genetic disorders, but ERT has been less successful for the correction of disorders with neurological manifestations. In this work, we have tested the functionality of nanoparticles (NP) composed of maltodextrin with a lipid core to bind and stabilize tyrosine hydroxylase (TH). This is a complex and unstable brain enzyme that catalyzes the rate-limiting step in the synthesis of dopamine and other catecholamine neurotransmitters. We have characterized these TH-loaded NPs to evaluate their potential for ERT in diseases associated with TH dysfunction. Our results show that TH can be loaded into the lipid core maltodextrin NPs with high efficiency, and both stability and activity are maintained through loading and are preserved during storage. Binding to NPs also favored the uptake of TH to neuronal cells, both in cell culture and in the brain. The internalized NP-bound TH was active as we measured an increase in intracellular L-Dopa synthesis following NP uptake. Our approach seems promising for the use of catalytically active NPs in ERT to treat neurodegenerative and neuropsychiatric disorders characterized by dopamine deficiency, notably Parkinson's disease.

Preparation of active polysaccharide-loaded maltodextrin nanoparticles and their stability as a function of ionic strength and pH

Active polysaccharides (APs) are known to have a wide variety of biological functions, such as anti-viral, anti-oxidant, hypoglycemic, and lipid-lowering effects. However, the extremely low bioavailability of APs restricts their bioactivity in vivo; therefore, the development of a biopolymer nanoparticle carrier is a promising solution. For the first time, we have successfully prepared maltodextrin nanoparticles (MNPs) with controllable particle sizes. The influence of different emulsifier types and volume ratios of a maltodextrin solution to absolute ethanol on the morphology and size of the MNPs was examined, and the smallest MNPs (30–90 nm) were obtained when the volume ratio was 1:10 and the emulsifier was Tween 80. Furthermore, tea, pumpkin, and balsam pear polysaccharides were loaded on the MNPs with loading efficiencies of 63.5, 68.7, and 72.1%, respectively. Compared with the MNPs, the AP-loaded MNPs were more stable in a high salt content, or under a gastric pH of 1.2 and physiological pH of 7.4 conditions. These MNPs may serve as effective nanocarriers by delivering APs to enhance their bioavailability.