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Poly lactic-co-glycolic acid (PLGA) is an ideal polymer for the delivery of small and macromolecule drugs. Conventional preparation methods of PLGA nanoparticles (NPs) result in poor control over NPs properties. In this research, a microfluidic mixer was designed to produce insulin-loaded PLGA NPs with tuned properties. Importantly; aggregation of the NPs through the mixer was diminished due to the coaxial mixing of the precursors. The micromixer allowed for the production of NPs with small size and narrow size distribution compared to the double emulsion solvent evaporation (DESE) method. Furthermore, encapsulation efficiency and loading capacity indicated a significant increase in optimized NPs produced through the microfluidic method in comparison to DESE method. NPs prepared by the microfluidic method were able to achieve a more reduction of trans-epithelial electrical resistance values in the Caco-2 cells compared to those developed by the DESE technique that leads to greater paracellular permeation. Compatibility and interaction between components were evaluated by differential scanning calorimetry and fourier transform infrared analysis. Also, the effect of NPs on cell toxicity was investigated using MTT test. Numerical simulations were conducted to analyze the effect of mixing patterns on the properties of the NPs. It was revealed that by decreasing flow rate ratio, i.e. flow rate of the organic phase to the flow rate of the aqueous phase, mixing of the two streams increases. As an alternative to the DESE method, high flexibility in modulating hydrodynamic conditions of the microfluidic mixer allowed for nanoassembly of NPs with superior insulin encapsulation at smaller particle sizes.

Purpose: Tuberculosis, a cost and life threatening disease, was being subjected for improving vaccine strategies beyond BCG. Thus, a novel particulate delivery system using alginate-coated chitosan nanoparticles including PPE17 protein and CpG were administered through intranasal (IN) and subcutaneous (SC) routes., Methods: The encapsulated nanoparticles were first characterized for size, surface charge, encapsulation efficiency and in vitro release of PPE17 antigen. The nanoparticles were then administered intranasal and subcutaneously to evaluate the induction of systemic and/or mucosal immune responses in mice., Results: According to our result, the mean size of nanoparticles was measured about 427 nm, and exhibited a negative zeta potential of -37 mV. Following subcutaneous and intranasal administration, the results from cytokines assay showed that an increasing in the level of IFN-γ, and adversely a decrease in the level of IL-4 (presumptive Th1 biased immune response) was happened and also a notable elicitation in IL-17 cytokine was observed., Conclusion: In conclusion, our study demonstrated that alginate-coated chitosan nanoparticles showed to be an effective way to improve BCG efficiency as booster strategy for subcutaneous vaccine, and also can induce strong immune responses as prime strategy through intranasal vaccination., (Copyright © 2021. Published by Elsevier Inc.)

The smart self-regulated drug delivery systems for insulin administration are desirable to achieve glycemic control, and decrease the long-term micro- and macro vascular complications. In this study, we developed an injectable nano-complex formulation for closed-loop insulin delivery after subcutaneous administration and release of insulin in response to increased blood glucose levels. The nano-complex was prepared by mixing oppositely charged chitosan and PLGA nanoparticles. PLGA nanoparticles were prepared using double-emulsion solvent diffusion method, and were loaded with glucose oxidase (GOx) and catalase (CAT) enzymes. These negatively charged particles decrease micro-environmental pH, by gluconic acid production in the glucose molecules presence. Positively charged chitosan nanoparticles were prepared using ionic gelation method, and were loaded with insulin. These nanoparticles (NPs) released insulin by dissociation in acidic pH caused by the GOx activity. Following in vitro studies, in vivo evaluation of nano-complex formulations in streptozocin induced diabetic rats showed significant glycemic regulation up to 98 h after subcutaneous administration., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this investigation, the immunogenicity of HTLV-1 fusion epitope-loaded PLGA nanoparticles (NPs) was assessed in the absence or presence of co-encapsulated CpG ODN adjuvant, in a mice model. For this purpose, the multi-epitope chimera including Tax, env, and gag immunodominant HTLV-1 epitopes was encapsulated in biodegradable PLGA NPs with or without CpG adjuvant. PLGA nanospheres produced by a double emulsion method had a size of <200 nm, and encapsulation efficiency of chimera antigen was 85%. The release profile of radiolabeled chimera indicated that only 17.4% and 20.1% of chimera were released from PLGA NPs without or with co-encapsulated CPG ODN during one month, respectively. The PLGA formulations significantly elevated titers of IgG1, IgG2a, and sIgA antibodies, as well as IL-10, and IFN-γ cytokines and also reduced the amount of TGF-β1 production relative to the other vaccines. Additionally, co-delivery of chimera and CpG ODN in PLGA NPs significantly promoted cellular and mucosal responses compared to the incorporation of CpG and chimera antigen. In summary, these results revealed that the sustained release of chimera from PLGA as an efficient polymeric system elicited potent cell-mediated and mucosal immunity without inflammatory responses against HTLV-1. Therefore, the proper design of vaccine formulation and immunization strategy are crucial factors to construct an efficient vaccine., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Due to initiation of Mycobacterium tuberculosis infection via the mucosal tissue of the respiratory tract, intranasal administration of new tuberculosis vaccines is highly regarded to enhance mucosal immunity. Our outline was evaluation of mucosal and systemic immune responses in BALB/c mice after nasal delivery of HspX/EsxS fused antigen of Mycobacterium tuberculosis along with MPLA adjuvant entrapped in PLGA:DDA hybrid nanoparticles., Methods: In this study, the double emulsion solvent evaporation method (w/o/w) was used to prepare different nanoparticle formulations containing HspX/EsxS protein and MPLA. Three weeks after the last nasal immunization of BALB/c mice, IgA antibody levels in nasal lavage and IFN-γ, IL-4, IL-17 and TGF-β cytokines in supernatant of cultured splenocytes and also serum IgG1 and IgG2a titers were evaluated using ELISA method., Results: Our results indicated that nasal vaccination with PLGA:DDA nanoparticles loaded with HspX/EsxS protein±MPLA, both with and without a prime dose of BCG could provide efficient Th1, Th17, IgA, IgG1 and IgG2a immune responses., Conclusion: These findings demonstrate that both PLGA:DDA hybrid nanoparticles as carrier/adjuvant and MPLA as adjuvant, could efficiently induce mucosal and systemic immune responses against HspX/EsxS antigen, alone or as a booster for BCG., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This research aims to characterization of soluble soybean polysaccharide (SSPS) and development of a biodegradable SSPS nanocomposites prepared using various concentrations of TiO 2 nanoparticles. 13 C NMR suggested that backbone of SSPS is rhamnogalacturonan [1→4)-α-GalAp-(1/2)-α Rhap(1→]. Weight average molecular weight, number average molecular weight (Mn) and polydispersity index (PDI) of SSPS were found to be 2.54×10 6 g/mol, 5.54×10 6 g/mol, and 4.5, respectively. The intrinsic viscosity of SSPS (0.33) was lower than most of hydrocolloids. With increasing TiO 2 concentration, the water solubility, moisture content and water-vapor permeability (WVP) of SSPS-based nanocomposite films decreased. TiO 2 addition led to an increase in the melting temperature to a maximum of 132°C for the SSPS nanocomposite with 5wt% TiO 2 . With increasing TiO 2 concentrations from 5 to 15wt%, the melting temperature declined from 24 to 19°C. There were no significant agglomerates when the TiO 2 concentrations were increased to 5wt%; however, when the concentration reached 15wt%, agglomerations were observed. With addition of TiO 2 nanoparticles, tensile strength increased but elongation at break decreased. SSPS-based nanocomposite films demonstrated a promising range of antimicrobial activity. The current research clearly introduces a new antimicrobial composite which is potentially useful to prevent and treat infections., (Copyright © 2018 Elsevier B.V. All rights reserved.)

It has become important to explore more efficient and feasible influenza vaccines, since epidemics of influenza virus cause hundreds of thousands of deaths all around the world. Improving immunogenicity of parentral influenza vaccines has given rise to mucosal delivery routes. In this study, alginate nanoparticles (NPs) were efficiently synthetized by ionic gelation method and influenza virus and CpG ODN or Quillaja Saponin (QS) adjuvants were actively incorporated into alginate NPs. The prepared particles were evaluated for both humoral and cellular immune responses in rabbits' nostrils. The vaccination started with a prime dose and followed by three boosters (two intranasal (IN) on days 45 and 60 and the last dose, intramuscular (IM) on day 75). HAI titer had increased in all the samples; although, only in the group received WV + CPG suspension reached to the protective HAI titer. All the immunized rabbits elicited significantly high sIgA levels on day 75, compared to the negative and the IM groups. At the end of the study, IN administration of CpG ODN adjuvant with virus antigen induced higher IgG level than the groups vaccinated with alginate NPs with or without CpG ODN (P < 0.001). As for the cellular immunity, CpG ODN was capable of inducing significant levels of IL-4 and TNF-α, either through inoculation along with the virus suspension or as incorporated in alginate NPs. According to the obtained data, CpG ODN adjuvant showed higher immunogenic potential as part of a vaccine delivery system than QS. Moreover, applying alginate polymer as a nasal delivery system carrier was not deemed immunogenic against influenza whole virus., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Chitosan-coated ISCOMATRIX nanoparticles co-administrated with PR8 influenza virus were successfully developed via a lipid film hydration method to evaluate their in vivo immuniadjuvant potential in immunization against influenza. The prepared ISCOMATRIX (ISC) and chitosan-coated ISCOMATRIX (ISC-CIT) showed a particle size of 171 and 233 nm with a zeta potential of -9.47 and +5.65, respectively. Furthermore, ISC-CIT formulations were co-administered with PR8 antigen (PR8-ISC-CIT) and their immunogenicity was investigated after intranasal and intramuscular immunization of BALBc/mice. The PR8-ISC formulation elicited more IFN-γ after intranasal or intramuscular administration compared with PR8-ISC-CIT formulation. In contrast, although PR8-ISC-CIT formulation administered by intranasal route secreted more IFN-γ, it significantly decreased the IgG2a/IgG1 ratio and a less immune response was induced. Altogether, the ISC-adjuvanted influenza PR8 antigen could be considered as a powerful intramuscular antigen delivery system for producing a variety of prophylactic and therapeutic vaccines.

A superparamagnetic iron oxide nanoparticles (SPIONs)/doxorubicin (Dox) co-loaded poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles targeted with AS1411 aptamer (Apt) against murine C26 colon carcinoma cells is successfully developed via a modified multiple emulsion solvent evaporation method for theranostic purposes. The mean size of SPIO/Dox-NPs (NPs) was 130nm with a narrow particle size distribution and Dox loading of 3.0%. The SPIO loading of 16.0% and acceptable magnetic properties are obtained and analyzed using thermogravimetric and vibration simple magnetometer analysis, respectively. The best release profile from NPs was observed in PBS at pH 7.4, in which very low burst release was observed. Nucleolin is a targeting ligand to facilitate anti-tumor delivery of AS1411-targeted NPs. The Apt conjugation to NPs (Apt-NPs) enhanced cellular uptake of Dox in C26 cancer cells. Apt-NPs enhance the cytotoxicity effect of Dox followed by a significantly higher tumor inhibition and prolonged animal survival in mice bearing C26 colon carcinoma xenografts. Furthermore, Apt-NPs enhance the contrast of magnetic resonance images in tumor site. Altogether, these Apt-NPs could be considered as a powerful tumor-targeted delivery system for their potential as dual therapeutic and diagnostic applications in cancers., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Effective encapsulation of drugs into the delivery systems could increase the efficiency of nanoparticles in prevention and treatment of diseases., Objective: The purpose of this study was to compare the different methods for determination of encapsulation efficiency of a model protein in the PLGA nanoparticles., Methods: The various direct methods include dichloromethane, acetonitrile, modified acetonitrile and NaOH based extraction and radioactive methods were used to directly calculate the encapsulation efficiency of the loaded protein in the PLGA nanoparticles. Furthermore, indirect methods include BCA, Fluorescent and radioactive methods were compared., Results: The encapsulation efficiencies determined by indirect methods include dichloromethane, acetonitrile, modified acetonitrile, NaOH based extraction and radioactive methods were 12.62% ± 1.97, 17.43% ± 2.51, 64.69% ± 4.31, 86.36% ± 2.25 and 90.15% ± 1.78, respectively. Moreover, the encapsulation efficiencies determined by indirect methods include BCA, fluorescent and radioactive methods were 81.46% ± 1.92, 88.23% ± 1.15 and 89.6% ± 1.9, respectively., Conclusions: Among the results obtained by indirect methods, radioactive and fluorescent methods showed more reliable. Moreover, NaOH and radioactive methods were the most reliable methods among the direct methods.

To prevent the spread of HTLV-I (Human T-lymphotropic virus type 1), a safe and effective vaccine is required. To increase immune responses against the peptide antigens can be potentiated with polymer-based nanoparticles, like chitosan (CHT) and trimethylchitosan (TMC), as delivery system/adjuvant. CHT and TMC nanoparticles loaded with recombinant proteins (env23 & env13) of gp46 were prepared by direct coating of antigens with positively charged polymers. The size of CHT and TMC nanoparticles (NPs) loaded with each antigen was about 400 nm. The physical stability of NPs was followed for 4 weeks. Both formulations showed to be stable for about 15 days. The immunogenicity of NPs loaded with antigens was studied after nasal and subcutaneous immunization in mice. Three immunizations (7.5 μg antigen) were performed with 2 weeks intervals. Two weeks after the last booster dose, sera IgG subtypes were measured. After subcutaneous administration, for both nanoparticulate antigens, serum IgG1 and IgGtotal levels were higher than antigen solution (P < 0.001). After nasal administration, for env23, IgG2a levels and IgG2a/IgG1 ratio was significantly higher than groups with subcutaneous administration (P < 0.001). Both nanoparticles showed good immunoadjuvant potential. Env23 antigen was a better candidate for vaccination against HTLV-I, as it induced higher cellular immune responses, compared with env13., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Delivery to the lungs is an efficient way to deliver drugs directly to the site of action or to the blood circulation. Because of limitations of direct administration of free drugs, particulate drug delivery systems such as DPI formulations based on nanoparticles (NPs) have been of interest for pulmonary drug delivery. The prolonged residence of NPs in the lungs due to ability to escape from the clearance mechanisms such as mucociliary escalator, macrophage uptake (a size of 1-2 µm is ideal for macrophage phagocytosis), and translocation to the systemic circulation is amongst the key advantages of NPs. By this approach, the controlled pulmonary delivery of drugs, peptides, proteins, genes, siRNA, and vaccines is possible. Both natural (albumin, gelatin, alginate, collagen, cyclodextrin, and chitosan) and synthetic (poly (lactide-co-glycolide) (PLGA), polyacrylates and polyanhydrides) polymers have been used in formulation of pulmonary nanovectors. As direct pulmonary administration of NPs is not feasible, by using the safe excipients, NPs could be converted to dry powder inhaler (DPI) formulations. These can provide a promising deposition and stability of NPs. In this article, the DPI formulations based on polymeric nanoparticles have been reviewed and categorized based on the polymer type used for preparation of NPs.

Context: Methicillin-resistant Staphylococcus aureus (MRSA) infection with its high incidence is responsible for nosocomial infections. MRSA strains resistant to multiple antibiotics have emerged increasingly. Recently, combination therapy and efficient drug delivery systems are developed to treat infections., Objective: The aim of the present study was to evaluate antibacterial activities of combination of oleic acid and gentamicin against MRSA, in both free and liposomal forms, and in comparison with vancomycin., Materials and Methods: The antibacterial activities against MRSA ATCC 43300 were assessed by the determination of minimum inhibitory concentration (MIC), MBC, and Fractional Inhibitory Concentration Index (FICI). The time-kill assays were performed to evaluate the potency of antibacterial agents. Nanoliposomal formulations of gentamicin, oleic acid, and combination of gentamicin with oleic acid were prepared by the dehydration-rehydration (DRV) method and characterized for size, zeta potential, and encapsulation efficiency., Results: MIC values of gentamicin and oleic acid were 19.5 and >250 µg/ml, respectively. Synergetic effects were observed by the gentamicin and oleic acid combination; FICI was 0.5. Following incorporation of gentamicin into liposomal gentamicin and liposomal combination, the MIC values were reduced 15- and 27-fold, respectively. In comparison with vancomycin, liposomal combination was more effective in bacterial inhibition and killing. Liposomal combination was the most effective formula in time-kill study., Discussion and Conclusion: Liposomal formulation showed a higher antibacterial activity in comparison with the free forms and vancomycin. These carriers can improve antimicrobial activity as well as reducing the effective concentration required and inducing rapid bacterial clearance.

The present work was conducted to develop a new polysaccharide‐based encapsulation system via electrostatic interactions between Prunus armeniaca gum exudates (PAGE) and Ca2+ ions to enhance the biological activity and bioavailability of curcumin. The effects of different levels of pH (6, 7, and 8) and ion concentrations (1, 3, and 5) on the particle diameter and surface charge of the samples were examined. The encapsulation efficiency in the PAGE‐based nanoparticles was realized to be 86.1%, indicating the encapsulation technique applied in this study was effective to entrap most of the curcumin within the PAGE matrix. The nanoparticles showed a smooth surface with spherical shape. Fourier transform infrared spectroscopy (FT‐IR) and X‐ray diffraction (X‐ray) studies confirmed the formation of polyelectrolyte complexation. The cumulative release of curcumin in simulated gastrointestinal tract was less than 75%, revealing a gradual release trend. Both pure curcumin and curcumin‐loaded nanoparticles were toxic to the cancer cell lines. [ABSTRACT FROM AUTHOR]

In the present work, the effect of various concentrations of SiO2 nanoparticles (5, 10, and 15%) on physicochemical and antimicrobial properties of soluble soybean polysaccharide (SSPS)‐based film was investigated. Then, the migration of SiO2 nanoparticles to ethanol as a food simulant was evaluated. Subsequently, curcumin was added to the nanocomposite formulation to sense the pH changes. Finally, the cytotoxicity of the developed packaging system was investigated. With increasing nanoparticle concentration, the film thickness, water solubility, and water vapor permeability decreased and mechanical performance of the films improved. SSPS/SiO2 nanocomposite did not show antibacterial activity. SEM analysis showed that SiO2 nanoparticles are uniformly distributed in the SSPS matrix; however, some outstanding spots can be observed in the matrix. A very homogeneous surface was observed for neat SSPS film with Ra and Rq values of 3.48 and 4.26, respectively. With the incorporation of SiO2 (15%) into SSPS film, Ra and Rq values increased to 5.67 and 5.98, respectively. Small amount of SiO2 nanoparticles was released in food simulant. The nanocomposite incorporated with curcumin showed good physical properties and antibacterial activity. A strong positive correlation was observed between TVBN content of shrimp and a* values of the films during storage time (Pearson's correlation = 0.985). [ABSTRACT FROM AUTHOR]

Objective(s): A new strategy in recent studies is using effective tuberculosis (TB) subunit vaccines combined with appropriate carriers and adjuvants which have shown promising results in preclinical and clinical studies. The aim of the present study was to evaluate the PLGA:DDA hybrid nanoparticles (NPs) for subcutaneous delivery of a novel multistage subunit vaccine along with MPLA adjuvant against Mycobacterium tuberculosis (M. tuberculosis). Materials and Methods: PLGA and PLGA:DDA NPs containing HspX/EsxS fusion protein and MPLA were prepared by double emulsion method (w/o/w). After characterization, these NPs were subcutaneously administered to BALB/c mice aged 6-8 weeks old. Immunogenicity of formulations were assessed by measuring the level of IFN-γ, IL-4, IL-17 and TGF-β cytokines as well as IgG1, IgG2a and IgA antibodies using ELISA. Results: Both particles had spherical shape and smooth surface with 316.7±12.7 nm in size, surface charge of -33±1.7 mV, and encapsulation efficiency of 92.2±2% for PLGA NPs and 249.7±16.7 nm in size, surface charge of 39±1.8 mV, and encapsulation efficiency of 35.7±1.4% for PLGA:DDA NPs. The highest IFN-γ response and also IgG2a and IgG1 antibodies titers were observed in groups immunized with PLGA:DDA/HspX/EsxS/MPLA and PLGA:DDA/HspX/EsxS/MPLA as booster as well as PLGA:DDA/HspX/EsxS and PLGA:DDA/HspX/EsxS as booster. Conclusion: With regard to effective induction of IFN-γ and IgG2a immune responses, PLGA:DDA hybrid NP along with MPLA adjuvant have good potentials for improving the immunogenicity of HspX/EsxS multistage subunit vaccine as well as promoting BCG efficacy as a BCG prime-boost. [ABSTRACT FROM AUTHOR]

Polymeric particles and liposomes are efficient tools to overcome the low immunogenicity of subunit vaccines. The aim of the present study was formulation and optimization of a new cationic lipid-modified PLGA nanoparticles (NPs) as a delivery system for Mycobacterium tuberculosis HspX/EsxS fusion protein. The cationic lipid-modified PLGA NPs containing HspX/EsxS fusion protein were prepared using a modified double emulsion solvent evaporation method. Scanning electron microscopy and dynamic light scattering (DLS) tools were used to determine physical properties of hybrid NPs. A multi-level full factorial design was used to evaluate the influence of two factors of PLGA:DDA weight ratio (w/w) and PVA concentration (%) on size, surface charge, polydispersity index, encapsulation efficiency and yield. Finally, the optimal formulation was achieved based on desired responses. Mathematical models were obtained to indicate the relation between the studied factors and responses. The DDA concentration showed an increasing effect on surface charge and also a decreasing effect on particle size, encapsulation efficiency and yield. Higher amounts of DDA increased surface charge of NPs; however, the size, encapsulation efficiency and yield were decreased. The influence of various concentrations of PVA on different physical characteristics of PLGA:DDA hybrid NPs was variable. The optimal formulation consisted of 0.91 (55:5, w/w) weight ratio of PLGA:DDA and 0.5% PVA. The hybrid NPs showed acceptable particle size distribution, strong positive surface charge, prolonged antigen release and good encapsulation efficiency in comparison to PLGA alone. However, further preclinical and clinical studies are needed. [ABSTRACT FROM AUTHOR]

Among various vaccine candidates, subunit vaccines play an important role in immune protection against tuberculosis (TB). Calcium phosphate (CP) is considered as a strong inorganic adjuvant due to its great potential in increasing immune responses. The purpose of this study was to evaluate specific immune responses following the administration of trifusion-CP nanoparticles. The physiochemical properties of these nanoparticles, including morphology, particle size, zeta potential and adsorption rate, were measured in vitro. Subcutaneous immunization was performed three times on days 0, 14, and 28. Two weeks after the last administration, IFN-gamma, IL-4, and TGF-beta levels were measured by indirect enzyme linked immunosorbent assay (ELISA). The trifusion protein was successfully adsorbed onto calcium phosphate nanoparticles. The mean sizes of the resultant trifusion- CPN and CPN were 97.84 ± 12.08 and 67 ± 11.85 nm, respectively. CPN containing trifusion had stronger ability to induce IFN-gamma than the control groups. IL-4 and TGF-beta secretions in trifusion and trifusion-CPN groups were higher than those in the PBS group. However, there was no significant ( p > 0.05) difference in IL-4 and TGFbeta concentrations between trifusion group and trifusion- CPN group. Therefore, calcium phosphate nanoparticles are good candidates for immunization against TB because antigen can be easily adsorbed onto CPN and strong cellular immune responses against CPN-antigen can be stimulated. [ABSTRACT FROM AUTHOR]

Objective(s): It is proposed that particulate antigens could better interact with the antigen presenting cells (APCs). A fast, simple and scalable process for preparation of polymeric nanoparticles (NPs) is coating of charged antigenic particles, like viruses, with oppositely charged polymers. A second coating with a charged polymer could increase the stability and modify the immunomodulatory potentials of NPs. Materials and Methods: Negatively charged inactivated polio virus (IPV) was coated with cationic polymers, chitosan (CHT) and trimethylchitosan (TMC) by a simple incubation method. CHT: IPV and TMC: IPV NPs were coated by anionic polymer, sodium alginate (ALG). Physical characteristics and stability of NPs were studied. Cytocompatibility of NPs was checked with MTT assay. DC maturation study was used for evaluation of the NPs potential in interaction with DCs. Results: Among the various polymer to antigen ratios tested, the least size and PDI and the highest ZP was seen in TMC: IPV (2:1), CHT: IPV (2:1), ALG: TMC: IPV (2:2:1) and ALG: CHT: IPV (4:2:1). The physical stability of TMC: IPV and CHT: IPV was preserved until 15 days. After an early de-association of some part of coated alginate, ALG: CHT: IPV and ALG: TMC: IPC NPs were stable until the end of study (25th day). No one of the NPs formulations had a negative effect on cell viability. Compared with plain IPV, nanoparticulate IPV formulations failed to increase the expression of CD40 and CD86 markers of DCs. Conclusion: NPs prepared with simple and scalable method, had reasonable physical characteristics, stability and cytocompatibility and could be tested in vivo for their immunoadjuvant potential. [ABSTRACT FROM AUTHOR]

Abstract: Mucosal immunization offers various advantages over parenteral vaccination, but typically requires potent delivery systems and/or adjuvants to result in protective immunity. Here we report on the preparation of trimethylated chitosan (TMC) and chitosan (CHT) nanoparticles (NPs) loaded with hepatitis B surface antigen (HB), by a simple and scalable method. TMC:HB and CHT:HB NPs were prepared by direct coating of antigen by polymer. The impact of buffer, pH and tonicity of the dispersion medium on NPs’ polydispersity, zeta potential and association percentage of polymer with antigen was evaluated. Moreover, biological properties of both NPs were addressed in vitro by studying their effect on cell viability, transepithelial electrical resistance (TEER) and dendritic cell (DC) maturation. Finally, immunogenicity was assessed by evaluating IgG, IgG1, IgG2a, IgA titers and sIgA after both mucosal (nasal) as well intramuscular (i.m.) vaccination in a murine model. TMC:HB and CHT:HB NPs, prepared in acetate buffer pH 6.7 of three different tonicities, had comparable size, polydispersity, zeta potential and association percentage. TMC:HB NPs, but not CHT:HB NPs, had a mild negative effect on cell viability and TEER, and a considerable positive effect on DC maturation. After nasal and i.m. immunization, TMC:HB NPs in hypotonic medium and CHT:HB NPs in all media induced higher serum and nasal antibody titers compared with HB solution (P <0.001). After i.m. injection, both TMC:HB and CHT:HB NPs induced higher IgG and IgG2a titers compared with alum adsorbed HB (P <0.001). For CHT:HB NPs, the tonicity of the dispersion medium did not affect the mucosal and systemic immune responses. In conclusion, TMC NPs and CHT NPs are similarly potent mucosal immunoadjuvants for HB. Moreover, both polymers are potent immunoadjuvants for i.m. administered isotonic HB, resulting in higher IgG2a/IgG1 ratios compared with alum adjuvanted HB. [Copyright &y& Elsevier]

Superparamagnetic iron oxide (Fe 3 O 4 ) nanoparticles (SPIONs) were synthesized by co-precipitation using polyvinyl alcohol (PVA) as a capping agent under alkaline condition. The produced X-ray diffraction (XRD) pattern evidenced the presence of peaks corresponding to the inverse spinel structure of the prepared SPIONs. Debye-Scherrer and field emission scanning microscopy (FESEM) showed the prepared SPIONs to be well-defined with about < 50 nm size. Likewise, the superparamagnetic properties of the SPIONs measured by Vibrating Sample Magnetometer (VSM) showed high saturation magnetization (~ 65.36 emu/g). The in vitro cytotoxicity studies on Neuro2A and HUVEC cells have mentioned low toxic and non-toxic SPIONs, respectively in a range of concentrations (1.17–150 μg/ml), thus, we reckon that the synthesized SPIONs will have persistent utilization in different fields of medical applications. [ABSTRACT FROM AUTHOR]

In recent years, magnetic nanoparticles are increasingly studied and exploited for their potential applications as magnetic resonance imaging (MRI 1 1 Magnetic resonance imaging ) contrast agents, cancer treatment, targeted therapy, delivery vectors and hyperthermia. Todays, magnetic systems based on polymeric materials such as poly(lactic-co-glycolic acid) (PLGA 2 2 Poly(lactic-co-glycolic acid) ) have been of special interest for their biomedical applications. In this study, we achieved an effective method for encapsulation of sized-controlled oleic acid-coated superparamagnetic iron oxide (SPIO 3 3 Superparamagnetic iron oxide NPs 4 4 Nanoparticles ) into the PLGA nanospheres via a modified multiple emulsion solvent evaporation method (O 1 /W 1 /O 2 /W 2 5 5 Oil-in-water-in- oil-in-water ) resulted in development of the NPs with narrow size distribution and acceptable magnetic properties that are very vital and curtail at targeting and magnetic properties of NPs for both anti-cancer therapy and magnetic resonance imaging studies. The SPIO NPs and SPIO-PLGA nanospheres showed spherical morphology with narrow size distribution of 10 nm and 130 nm, respectively. SPIO-PLGA nanospheres with high SPIO loading of 18.0% and magnetic properties of 5.9 emu/g were obtained. Furthermore, SPIO-PLGA NPs enhance the contrast of relaxation time (T 1 6 6 Relaxation time )-weighted imaging in tumor site. The prepared SPIO NPs and magnetic PLGA nanosphere could be promising superparamagnetic nanoparticles for simultaneous diagnostic and therapeutic applications. [ABSTRACT FROM AUTHOR]

Abstract Reduction-responsive biodegradable micelles were prepared by linking of poly(ethylene glycol) and poly(ε‑caprolactone) with disulfide bond (PEG-SS-PCL) for co-delivery of superparamagnetic iron oxide (SPIO) nanoparticles (NPs) and an anticancer agent, doxorubicin (DOX). This amphiphilic diblock copolymer shows redox-responsive properties, which is arising from disulfide bonds throughout the main chain. The ability of these copolymers for self-assembly with oleic acid modified SPIONs can help to organize nanomicelles in aqueous solution. Doxorubicin (DOX) was loaded in the magnetic nanomicelles with a loading of 32%. Coarse-Grained Molecular Dynamics (CG-MD) simulation approach was exploited to reassure the construction of self-assembled PEG-PCL micelles in presence of oleic acid and water solvent while the hydrophobic and hydrophilic ratios of each block copolymer were equally chosen and each oleic acid was connected to Fe 3 O 4 nanoparticles. Our results confirmed the stability, cytocompatibility, magnetic and redox-responsive properties for these self-assembled nanomicelles and revealed that the DOX-SPION-loaded reduction-sensitive nanomicelles could be used in drug targeting to the cancer cells. Graphical abstract Unlabelled Image Highlights • Synthesized reduction-responsive biodegradable micelles poly(ethylene glycol)‑ b ‑poly(ε‑caprolactone) (PEG-SS-PCL) • Study loading Doxorubicin and SPION in nano micelles • Simulation PEG-PCL nano micelles and loading Fe 3 O 4 (linked with oleic acid) • Study cytotoxicity of nano micelles [ABSTRACT FROM AUTHOR]