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Different carrier systems have been investigated for myocardial delivery of biopharmaceuticals for heart disease. Here, we aimed to evaluate the heart retention and tissue response of liposomes intended for cardiac drug delivery. Liposomes were produced by the lipid thin film hydration method followed by sonication. Cytocompatibility tests were performed in murine L929 fibroblasts and H2c9 cardiomyocytes using the Alamar Blue assay. In vivo experiments were assessed in a model of myocardial infarction induced by isoproterenol in mice. Cardiac delivery of fluorescent liposomes (rhodamine B-labeled) with different mean sizes (165 nm, 468 nm, 1551 nm and 1954 nm) was performed by ultrasound-guided transthoracic injection. After three days, mice were euthanized for histological evaluation using optical and fluorescence microscopy. No cytotoxic lipid concentrations were determined in the range 9.3 - 120 µM for fibroblasts and cardiomyocytes exposed to liposomes. In vivo, large liposomes induced significant inflammation in myocardium compared with the control group (p 0.0001). In contrast, heart mice injected with 468 nm-sized liposomes exhibited a lower number of inflammatory cells. Still, a greater tissue retention 72 h post-injection was found. Therefore, this study demonstrated the feasibility of the echocardiography-guided percutaneous injection to deliver liposomes successfully into the myocardium in a minimally invasive manner. In addition, these findings indicate the potential of liposomes as carriers of biopharmaceuticals for myocardial delivery, supporting the development of further research on these delivery systems for heart disease.

Ivermectin is an FDA-approved broad-spectrum antiparasitic agent with demonstrated antiviral activity against a number of DNA and RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite this promise, the antiviral activity of ivermectin has not been consistently proven in vivo. While ivermectin's activity against SARS-CoV-2 is currently under investigation in patients, insufficient emphasis has been placed on formulation challenges. Here, we discuss challenges surrounding the use of ivermectin in the context of coronavirus disease-19 (COVID-19) and how novel formulations employing micro- and nanotechnologies may address these concerns., Graphical abstract Unlabelled Image, Highlights • Ivermectin is an FDA-approved antiparasitic agent, being currently investigated in COVID-19 patients • Ivermectin for COVID-19 is restrained by formulation challenges, whereas only oral dosage forms are available • The delivery of ivermectin by pulmonary route would provide high drug deposition in the airways and lungs • Expected efficacy by using aerosol micro- and nanocarriers containing ivermectin

Cashew nut allergy is the second most commonly reported tree nut allergy. Traditional allergen immunotherapy presents several clinical drawbacks that can be reduced by using nanoparticles-based allergen-delivery systems, modulating the immune response towards a protective one. In this context, the goal of this work was to assess the potential of poly(anhydride) nanoparticles (NP) for cashew nut oral immunization. Cashew nut allergens-loaded nanoparticles (CNE-NP) were prepared by solvent displacement method. After nanoparticles characterization, oral immunomodulation ability was evaluated in BALB/c mice. Our results demonstrated that CNE-NP induced a higher Th1/Th2 ratio in comparison with animals immunized with free cashew nut proteins. Indeed, a decrease in splenic Th2 cytokines (IL-4, IL-5, and IL-13), and an enhancement of pro-Th1 (IL-12 and IFN-γ) and regulatory (IL-10) cytokines was observed. Furthermore, mice orally immunized with CNE-NP presented an increased expansion of CD4+ T regulatory cells, such as CD4+Foxp3+ and CD4+LAP+, in the mesenteric lymph nodes. In conclusion, oral immunization with a single dose of poly(anhydride) nanoparticles loaded with cashew nut proteins leaded to a pro-Th1 and Treg immune response. Furthermore, their immunomodulatory properties could be introduced as a new approach for management of cashew nut allergy.

Despite the potential of Passiflora spp. as potential as source of bioactive compounds, poor aqueous solubility and stability issues restrict their use in pharmaceutical field. The most suitable approach to overcome such limitations is the development of formulations based on proper delivery systems. Among them, nanoemulsions have been widely used as carrier systems that can guarantee better cutaneous performance of herbal oils. This study evaluated physicochemical properties and cellular effects of seed oils from four varieties of wild Passiflora spp. The fatty acids profile of the seed oils was analyzed by gas chromatography and cell viability assay was performed on J774 macrophages. The nanoemulsions were prepared for the different seeds oils and cell proliferation was evaluated on HaCaT keratinocytes. The oils presented a predominance of unsaturated fatty acids, mainly linoleic acid (>65%) and no cytotoxic effects were observed on J774 cells up to 100 μg/mL. All nanoemulsions presented droplet size about 200 nm, narrow polydispersity index (

This work describes the development of a nanoemulsion composition suitable for the topical administration of vaccines based on outer membrane vesicles. The application onto bare skin of outer membrane antigens from Salmonella enterica (size between 20 and 100 nm), included in a nanoemulsion, induced a clear specific antibody response. In contrast to other semisolid formulations used (i.e. simple and polyethyleneglycol ointments), the occlusive effect provided by the nanoemulsion together with the penetration enhancer effect of Labrasol ® and Plurol ® oleique, increased antigen uptake by epidermal and transfollicular routes. Nevertheless, when the antigenic complex was loaded into poly(anhydride) nanoparticles and then incorporated in the nanoemulsion, the specific IgG response in serum was significantly lower. These results suggest that the higher size of nanoparticles (about 230 nm) and their non-deformable nature could hamper the arrival of the antigen to the immunological inducer sites when administered on the skin. Immunohistochemistry analysis confirmed that these bacterial vesicles were able to penetrate the skin reaching the dermis only when antigens were administered in the form of nanoemulsion. Further research will determine the full potential of this formulation for topical application of this specific type of vaccines.

Bacterial levan is a fructose homopolymer that offers great potential in biotechnological applications due to biocompatibility, biodegradability and non-toxicity. This biopolymer possesses diverse multifunctional features, which translates into a wide range of applicability, including in industry, consumer products, pharmaceuticals and biomedicine. Extensive research has identified great potential for its exploitation in human health. In addition, nanostructured systems have provided significant advances in the area of health, mainly with respect to disease diagnosis and treatment. While the functional properties of these natural polysaccharide-based polymers are desirable in these systems, research in this area has been limited to few natural polymers, such as chitosan, alginate and dextran, which obscures the true potential of levan in the production of nanostructured systems for biotechnological and medical applications. The present review considers the latest research in the field to focus on the use of levan as a promising biopolymer for the development of nanomaterials.

17-N-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) is an inhibitor of heat shock protein 90 (Hsp90), which has been studied in the treatment of cancer such as leukemia or solid tumors. Alternatively, 17-AAG may represent a promising therapeutic agent against leishmaniasis. However, the delivery of 17-AAG is difficult due to its poor aqueous solubility. For exploring the therapeutic value of 17-AAG, we developed solid lipid nanoparticles (SLN) by double emulsion method. SLN exhibited ~100 nm, PDI0.2 and zeta potential ~20 mV. In addition, SLN were morphologically spherical with negligible aggregation. The entrapment efficiency of 17-AAG into the lipid matrix reached at nearly 80%. In a separate set of experiments, fluorescent SLN (FITC-labeled) showed a remarkable macrophage uptake, peaking within 2 h of incubation by confocal microscopy. Regarding the drug internalization as critical step for elimination of intracellular Leishmania, this finding demonstrates an important feature of the developed SLN. Collectively, these data indicate the feasibility of developing SLN as potential delivery systems for 17-AAG in leishmaniasis chemotherapy.

Background: Peanut allergy is the most common cause of anaphylaxis and food-related death. However, there is currently no approved immunotherapy treatment. Hence, this warrants the need for relevant and convenient animal models to test for adequate immunotherapies. Materials & methods: In this study, we compared three mouse strains: CD1, BALB/c and C57, to select a model of peanut allergy. After that, we conducted then a therapeutic study using an immunogenic peanut extract encapsulated in nanoparticles made with polymer Gantrez® following the solvent displacement method. Results & conclusion: After implementing a dosing schedule with oral commercial peanut butter, the antibody responses, cytokine profiles and, above all, the anaphylaxis induced after a challenge with peanut proteins, showed that the outbred CD1 strain was the most susceptible to peanut sensitization. CD1 sensitized mice were orally immunized with three doses of the nanoparticle formulation capable of protecting them against the severe anaphylactic symptoms induced by the peanut challenge.

In the last decade, peanut allergy has increased substantially. Significant differences in the prevalence among different countries are attributed to the type of thermal processing. In spite of the high prevalence and the severe reaction induced by peanuts, there is no immunotherapy available. The aim of this work was to evaluate the potential application of poly(anhydride) nanoparticles (NPs) as immunoadjuvants for peanut oral immunotherapy. NPs loaded with raw or roasted peanut proteins were prepared by a solvent displacement method and dried by either lyophilization or spray-drying. After physicochemical characterization, their adjuvant capacity was evaluated after oral immunization of C57BL/6 mice. All nanoparticle formulations induced a balanced TH1 and TH2 antibody response, accompanied by low specific IgE induction. In addition, oral immunization with spray-dried NPs loaded with peanut proteins was associated with a significant decrease in splenic TH2 cytokines (interleukin 4 [IL-4], IL-5, and IL-6) and enhancement of both TH1 (gamma interferon [IFN-γ]) and regulatory (IL-10) cytokines. In conclusion, oral immunization with poly(anhydride) NPs, particularly spray-dried formulations, led to a pro-TH1 immune response.

Allergen-specific immunotherapy is based on the administration of allergens with the main disadvantage of inducing an allergic reaction. Within this context, we report the generation of an adjuvant and allergen-delivery system for peanut allergen immunotherapy with reduced IgE induction. Therefore, we prepared and characterized poly(anhydride) nanoparticles loaded with peanut proteins using the solvent displacement method, with some modifications in the manufacturing process. The precipitation of polymer was performed with either a mixture of ethanol and water or water. The resultant nanoparticles were dried by either freeze-drying or spray-drying, respectively. Poly(anhydride) nanoparticles loaded with peanut proteins were successfully developed, achieving both high encapsulation efficiency (70-80%) and manufacturing yield (60-80%). After intradermal immunization of mice (C57Bl/6) with peanut proteins incorporated into poly(anhydride) nanoparticles, a strong mixed T(H)1/T(H)2-type immune response was observed. Furthermore, we also provide, to our knowledge for the first time, clear evidence of the influence of formulation design on the immunostimulatory properties of nanoparticles. Taken together, our findings indicate that poly(anhydride) nanoparticles are efficient stimulators of immune responses and promising adjuvants and allergen-delivery systems applied for immunotherapy.

In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of allergic diseases. However, current allergen immunotherapy shows limitations concerning the long-term efficacy and safety due to local side effects and risk of anaphylaxis. Thus, effective and safe vaccines with reduced dose of allergen have been developed using adjuvants. Nevertheless, the use of adjuvants still has several disadvantages, which limits its use in human vaccines. In this context, several novel adjuvants for allergen immunotherapy are currently being investigated and developed. Currently, nanoparticles-based allergen-delivery systems have received much interest as potential adjuvants for allergen immunotherapy. It has been demonstrated that the incorporation of allergens into a delivery system plays an important role in the efficacy of allergy vaccines. Several nanoparticles-based delivery systems have been described, including biodegradable and nondegradable polymeric carriers. Therefore, this paper provides an overview of the current adjuvants used for allergen immunotherapy. Furthermore, nanoparticles-based allergen-delivery systems are focused as a novel and promising strategy for allergy vaccines.