Z-average Diameter Research Articles

Biosynthesis of copper nanoparticles; its characterization and efficacy against human pathogenic bacterium

Synthesis of nano-material with the controlled size and shape is the prime concern of research in nanotechnology. Recently, biosynthesis of metallic nano-particles has gained popularity owing to its eco-friendliness. Use of natural plant extracts in the preparation of nano-particles provides advancement over chemical and physical methods, due to its t is cost effectiveness and environment friendly nature. In the present work, copper nano-particles have been synthesized with simple and green technique by using Ocimum sanctum plant leaf extract as reducer as well as stabilizer. The size and shape of synthesized nano-particles were pigeonholed by particle size analyzer and SEM, further were characterized by EDS and FT-IR spectral technique for their elemental and chemical composition. The experimental results showed copper nano-particles having Z-average diameter of 122.7nm with higher stability and significantly higher antibacterial activities.

Development and evaluation of well-tolerated and tumor-penetrating polymeric micelle-based dry powders for inhaled anti-cancer chemotherapy

Despite the direct access to the lung offered by the inhalation route, drug penetration into lung tumors could remain an important issue. In this study, folate-polyethylene glycol-hydrophobically-modified dextran (F-PEG-HMD) micelles were developed as an effective pulmonary drug delivery system to reach and penetrate lung tumors and cancer cells. The F-PEG-HMD micelles were able to enter HeLa and M109-HiFR, two folate receptor-expressing cancer cell lines, in vitro, and in vivo after administration by inhalation to orthotopic M109-HiFR lung tumor grafted mice. Paclitaxel-loaded F-PEG-HMD micelles characterized in PBS by a Z-average diameter of ∼50nm and a zeta potential of ∼−4mV were prepared with an encapsulation efficiency of ∼100%. The loaded micelles reduced HeLa and M109-HiFR cell growth, with half maximal inhibitory concentrations of 37 and 150nM, respectively. Dry powders embedding the paclitaxel-loaded F-PEG-HMD micelles were developed by spray-drying. In vitro, good deposition profiles were obtained, with a fine particle fraction of up to 50% and good ability to re-disperse the micelles in physiological buffer. A polymeric micelle-based dry powder without paclitaxel was well-tolerated in vivo, as assessed in healthy mice by determination of total protein content, cell count, and cytokine IL-1β, IL-6, and TNF-α concentrations in bronchoalveolar lavage fluids.

Lipid-Core Nanocapsules Improved Antiedematogenic Activity of Tacrolimus in Adjuvant-Induced Arthritis Model.

Despite significant technological advances, rheumatoid arthritis remains an incurable disease with great impact on the life quality of patients. We studied the encapsulation of tacrolimus in lipidcore nanocapsules (TAC-LNC) as a strategy to enhance its systemic anti-arthritic properties. TAC-LNC presented unimodal distribution of particles with z-average diameter of 212 +/- 11, drug content close to the theoretical value (0.80 mg mL(-1)), and 99.43% of encapsulation efficiency. An in vitro sustained release was determined for TAC-LNC with anomalous transport mechanism (n = 0.61). In vivo studies using an arthritis model induced by Complete Freund's Adjuvant demonstrated that the animals treated with TAC-LNC presented a significantly greater inhibition of paw oedema after intraperitoneal administration. Furthermore, the encapsulation of TAC in lipid-core nanocapsules was potentially able to prevent hyperglycemia in the animals. In conclusion, TAC-LNC was prepared with 100% yield of nanoscopic particles having satisfactory characteristics for systemic use. This formulation represents a promising strategy to the treatment of rheumatoid arthritis in the near future.

Factors to Govern Soluble and Insoluble Aggregate-formation in Monoclonal Antibodies.

The aggregation formation of monoclonal antibodies as biopharmaceuticals induced by heat stress was evaluated by size-exclusion chromatography, and the formation rate was correlated with several physicochemical parameters of the antibodies to clarify the factors to govern the aggregate formation. The parameters we studied were: the melting temperature (Tm) and the standard enthalpy of the melting point (ΔmH°) evaluated by differential scanning calorimetry under given and common conditions; the wavelength (λmax) and the intensity (Fint) of the maximum fluorescence peak of 1-anilinonaphthalene-8-sulfonate as a probe dye; the z-average diameter (D) evaluated by dynamic light scattering; and the isoelectric point (pI) and the hydrophobic index (Hpho) of the complementarity determining region calculated from the amino acid sequence. Multivariate statistical analysis with these explanatory variables based on Akaike's information criterion indicates that the soluble aggregate formation is negatively correlated with Tm and pI, while the insoluble aggregate formation is positively correlated with Fint and pI. Based on these results, the mechanisms of the aggregate formation and methods to prevent the formation are discussed.

Characterization of progesterone loaded biodegradable blend polymeric nanoparticles

ABSTRACT: The encapsulation of progesterone in poly (hydroxybutirate-co-hydroxyvalerate) (PHBV), poly (ε-caprolactone) (PCL), poly (L-lactic acid) (PLLA) nanoparticles and PHBV/PCL and PHBV/PLLA blend nanoparticles was investigated in this research. Nanoparticles were produced by miniemulsion/solvent evaporation technique with lecithin as surfactant and were characterized regarding to z-average diameter (Dz) and polydispersity (PDI), progesterone recovery yield and encapsulation efficiency. Possible interactions between progesterone and the polymer matrices were investigated by Fourier Transform Infrared Spectroscopy (FTIR). High recoveries (up to 102.43±1.80% for the PHBV/PLLA blend) and encapsulation efficiencies (up to 99.53±0.04% for PCL) were achieved and the nanoparticles presented narrow size distribution (0.12±0.03 for PLLA). PCL nanoparticles (217.5±2.12nm) presented significant difference with the Dz from all the other formulations (P<0.05). The most evident interaction between progesterone and the nanoparticles polymeric matrix was found to PHBV/PCL due to the increase in the intensity of the band located in 1631 cm-1.

Physicochemical properties of whey protein, lactoferrin and Tween 20 stabilised nanoemulsions: Effect of temperature, pH and salt

Oil-in-water nanoemulsions were prepared by emulsification and solvent evaporation using whey protein isolate (WPI), lactoferrin and Tween 20 as emulsifiers. Protein-stabilised nanoemulsions showed a decrease in particle size with increasing protein concentration from 0.25% to 1% (w/w) level with Z-average diameter between 70 and 90nm. However, larger droplets were produced by Tween 20 (120–450nm) especially at concentration above 0.75% (w/w). The stability of nanoemulsions to temperature (30–90°C), pH (2–10) and ionic strength (0–500mM NaCl or 0–90mM CaCl2) was also tested. Tween 20 nanoemulsions were unstable to heat treatment at 90°C for 15min. WPI-stabilised nanoemulsions exhibited droplet aggregation near the isoelectric point at pH 4.5 and 5 and they were also unstable at salt concentration above 30mM CaCl2. These results indicated that stable nanoemulsions can be prepared by careful selection of emulsifiers.

Physicochemical and emulsion properties of edible protein concentrate from coconut (Cocos nucifera L.) processing by-products and the influence of heat treatment

The physicochemical and emulsion properties of the edible coconut protein concentrate (CPC) obtained from coconut wet processing by-products were evaluated in order to characterize the protein. Native CPC and heat-treated CPC (CPCH) were used as an oil-in-water emulsifier at a constant protein concentration of 0.2% (w/v) in systems containing 10% (v/v) virgin olive oil or sunflower oil at pH 6.9. Nutritionally, CPC (80.3% protein) contains all the essential amino acids and predominantly leucine, lysine and valine. The coconut proteins ranged in molecular weight from 15 to 220 kDa, with both 11S and 7S globulin present. The presence of CPC as an oil-in-water emulsifier enhanced the stability of the system, and the virgin olive oil-in-water emulsions with CPC showed a higher stability than the corresponding sunflower oil-in-water emulsions. Furthermore, CPCH showed a greater solubility, interfacial tension and emulsifying activity than CPC but with a reduced emulsifying stability, particle size distribution (D3,2) and flocculation. However, the protein secondary structures, zeta potential and Z-average diameter (D4,3) of CPC were not significantly different from CPCH. Thus, coconut wet processing by-products can be used as a source of protein for humans, and it is possible to use the functional ingredients in oil-in-water emulsion foods.

New dry powders for inhalation containing temozolomide-based nanomicelles for improved lung cancer therapy.

Besides the numerous advantages of a chemotherapy administered by the inhalation route for lung cancer therapy, dry powder for inhalation (DPI) offers many advantages compared to other techniques and seems to be a technique that is well-adapted to an anticancer treatment. DPI formulations were developed using the cytotoxic drug temozolomide and a new folate-grafted self-assembling copolymer, a conjugate of three components, folate-polyethylene glycol-hydrophobically-modified dextran (F-PEG-HMD). F-PEG-HMD was synthesized using carbodiimide-mediated coupling chemistry in three main steps. F-PEG-HMD was characterized by 1H-NMR, mass spectrometry and thermal analysis. F-PEG-HMD presented a critical micellar concentration in water of 4x10-7 M. F-PEG-HMD nanomicelles were characterized by a trimodal particle size distribution with Z-average diameter of 83±1nm in water. Temozolomide-loaded nanomicelles were prepared by solubilization of F-PEG-HMD in the presence of temozolomide. Temozolomide solubility in water was increased in the presence of F-PEG-HMD (2-fold increase in molar solubility) which could potentially lead to increased local concentrations in the tumor site. The temozolomide-loaded F-PEG-HMD nanomicelles were characterized by a Z-average diameter of ~50 to ~60nm, depending on the F-PEG-HMD concentration used. The nanomicelles were then spray-dried to produce dry powders. Temozolomide remained stable during all the formulation steps, confirmed by similar invitro anticancer properties for the DPI formulations and a raw temozolomide solution. Two of the developed DPI formulations were characterized by good aerodynamic properties (with a fine particle fraction of up to 50%) and were able to release the F-PEG-HMD nanomicelles quickly in aqueous media. Moreover, invitro, the two DPI formulations showed wide pulmonary deposition in the lower respiratory tract where adenocarcinomas are more often found. The present study, therefore, shows that F-PEG-HMD-based dry powders for inhalation could constitute an interesting drug delivery system able to release nanomicelles that are useful in adenocarcinomas that overexpress folate receptors.

Formation of complexes between hematite nanoparticles and a non-conventional galactomannan gum. Toward a better understanding on interaction processes

The physicochemical characteristics of hematite nanoparticles related to their size, surface area and reactivity make them useful for many applications, as well as suitable models to study aggregation kinetics. For several applications (such as remediation of contaminated groundwater) it is crucial to maintain the stability of hematite nanoparticle suspensions in order to assure their arrival to the target place. The use of biopolymers has been proposed as a suitable environmentally friendly option to avoid nanoparticle aggregation and assure their stability. The aim of the present work was to investigate the formation of complexes between hematite nanoparticles and a non-conventional galactomannan (vinal gum — VG) obtained from Prosopis ruscifolia in order to promote hematite nanoparticle coating with a green biopolymer. Zeta potential and size of hematite nanoparticles, VG dispersions and the stability of their mixtures were investigated, as well as the influence of the biopolymer concentration and preparation method. DLS and nanoparticle tracking analysis techniques were used for determining the size and the zeta-potential of the suspensions. VG showed a polydispersed size distribution (300–475nm Z-average diameter, 0.65Pdi) and a negative zeta potential (between −1 and −12mV for pH2 and 12, respectively). The aggregation of hematite nanoparticles (3.3mg/L) was induced by the addition of VG at lower concentrations than 2mg/L (pH5.5). On the other hand, hematite nanoparticles were stabilized at concentrations of VG higher than 2mg/L. Several phenomena between hematite nanoparticles and VG were involved: steric effects, electrostatic interactions, charge neutralization, charge inversion and polymer bridging. The process of complexation between hematite nanoparticles and the biopolymer was strongly influenced by the preparation protocols. It was concluded that the aggregation, dispersion, and stability of hematite nanoparticles depended on biopolymer concentration and also on the way of preparation and initial physicochemical properties of the aqueous system.

Soy glycinin as food-grade Pickering stabilizers: Part. I. Structural characteristics, emulsifying properties and adsorption/arrangement at interface

The development of food-grade Pickering stabilizers has recently attracted growing interests, due to their potential applications in food and pharmaceutical formulations. We report that glycinin (SG), one of major globulins in soy proteins, exhibits a very promising potential to perform as a kind of novel food-grade Pickering stabilizers for oil-in-water emulsions. The unheated SG at pH 7.0 was mainly present in the nanoparticle form (with a z-average diameter of 57 nm), and the heating at 90 or 100 °C considerably increased the particle size and surface hydrophobicity (by 5–6 fold) of the nanoparticles. The heating also remarkably changed the pattern of intra-particle interactive forces, and for the heated SG nanoparticles, their internal structure was mainly maintained by both hydrophobic interactions and disulfide bonds. The heating greatly improved the emulsification performance of the nanoparticles, especially at high concentrations (e.g. > 0.5%, w/v), as well as the stability of the corresponding emulsions against coalescence and creaming. As compared with the SG preparation heated at 90 °C, that at 100 °C exhibited a higher effectiveness to pack at the interface. The better emulsification performance for the heated SG preparations was closely associated with their more efficient packing and higher diffusion (or initial adsorption) at the interface. The results indicated that SG nanoparticles, unheated or heated, could be applied as a kind of Pickering stabilizers for oil-in-water emulsions; as compared to the unheated SG, the heated SG nanoparticles exhibited much better interfacial and emulsifying properties, thus imparting a better Pickering stabilization for the emulsions.

Effect of CaCl2 on denaturation and aggregation of silver carp myosin during setting

The effect of CaCl2 on denaturation and aggregation of silver carp myosin incubated at 40°C was investigated by circular dichroism spectroscopy, surface hydrophobicity (S0-ANS), total sulfhydryl (SH) group content, zeta potential, turbidity, z-average diameter (dz), and dynamic rheological analysis. During setting at 40°C, both CaCl2 and heating induced conformational changes of the fish myosin, and exposure of more hydrophobic amino acid residues and free SH groups, followed by myosin aggregation via hydrophobic interactions and disulfide bonds. Additionally, turbidity and dz of myosin increased significantly with increasing CaCl2 concentration, and the added CaCl2 further increased the extent and rate of aggregation of myosin by promoting the formation of Ca bridges. Myosin with 60mM CaCl2 showed the maximal G′ value and the highest rate of G′ development. However, the G′ value would decrease with an excessive amount of CaCl2 (100mM).

Hydrogel nanoparticle encapsulated plasmid as a suitable gene delivery system

To facilitate the delivery of genetic material, the use of appropriate carriers such as polymers is necessary. Nanoparticles comprising of chitosan-alginate polymers were formed through pregel preparation method. Chi/Alg nanoparticles had a mean Z-Average diameter of 161.8 nm and mean zeta 29.3 mV, respectively. The ability of plasmidcomplex in preventing DNA migration showed Chi/Alg nanoparticles have great capacity to maintain plasmid. The efficiency of nanoparticles for transfection of pEGFP-N1 plasmid in the cultured HEK 293 cells was measured by flow cytometry. Cell viability assays indicated that nanoparticles had no toxic effect on HEK 293 cells after 4 or 24 h. Our suitable candidate for gene delivery would be Alg/Chi nanoparticles.

Eugenol oil nanoemulsion: antifungal activity against Fusarium oxysporum f. sp. vasinfectum and phytotoxicity on cottonseeds

The current research deals with the formulation and characterization of bio-based oil-in-water nanoemulsion. The formulated eugenol oil nanoemulsion was characterized by dynamic light scattering, stability test, transmission electron microscopy and thin layer chromatography. The nanoemulsion droplets were found to have a Z-average diameter of 80 nm and TEM study reveals the spherical shape of eugenol oil nanoemulsion (EON). The size of the nanoemulsion was found to be physically stable up to more than 1-month when it was kept at room temperature (25 °C). The TEM micrograph showed that the EON was spherical in shape and moderately mono or di-dispersed and was in the range of 50–110 nm. Three concentrations of the nanoformulation were used to evalute the anti-fusarium activity both in vitro and in vivo experiments. SDS-PAGE results of total protein from the Fusarium oxysporum f. sp. vasinfectum (FOV) isolate before and after treatment with eugenol oil nanoemulsion indicate that the content of extra cellular soluble small molecular proteins decreased significantly in EON-treated fungus. Light micrographs of mycelia and spores treated with EON showed the disruption of the fungal structures. The analysis of variance (ANOVA) for Fusarium wilt incidence indicated highly significant (p = 0.000) effects of concentration, genotype, and their interaction. The difference in wilt incidence between concentrations and control was not the same for each genotype, that is, the genotypes responded differently to concentrations. Effects of three EON concentration on germination percentage, and radicle length, were determined in the laboratory. One very interesting finding in the current study is that cotton genotypes was the most important factors in determining wilt incidence as it accounted for 93.18 % of the explained (model) variation. In vitro experiments were conducted to evaluate the potential phytotoxic effect of three EON concentrations. Concentration, genotype and concentration x genotype interaction were all highly significant sources of variation in seed germination; however, interaction was the first in importance as a source of variation followed by the concentration, while genotype was the least important source of variation. These results suggest the potential use of eugenol oil nanoemulsion for protecting seedcotton from Fusarium wilt infection.

Poly-(lactic-co-glycolic-acid)-based particulate vaccines: Particle uptake by dendritic cells is a key parameter for immune activation

Poly(lactic-co-glycolic acid) (PLGA) particles have been extensively studied as biodegradable delivery system to improve the potency and safety of protein-based vaccines. In this study we analyzed how the size of PLGA particles, and hence their ability to be engulfed by dendritic cells (DC), affects the type and magnitude of the immune response in comparison to sustained release from a local depot. PLGA microparticles (MP, volume mean diameter≈112μm) and nanoparticles (NP, Z-average diameter≈350nm) co-encapsulating ovalbumin (OVA) and poly(I:C), with comparable antigen (Ag) release characteristics, were prepared and characterized. The immunogenicity of these two distinct particulate vaccines was evaluated in vitro and in vivo. NP were efficiently taken up by DC and greatly facilitated MHC I Ag presentation in vitro, whereas DC cultured in the presence of MP failed to internalize significant amounts of Ag and hardly showed MHC I Ag presentation. Vaccination of mice with NP resulted in significantly better priming of Ag-specific CD8+ T cells compared to MP and OVA emulsified with incomplete Freund's adjuvant (IFA). Moreover, NP induced a balanced TH1/TH2-type antibody response, compared to vaccinations with IFA which stimulated a predominant TH2-type response, whereas MP failed to increase antibody titers. In conclusion, we postulate that particle internalization is of crucial importance and therefore particulate vaccines should be formulated in the nano- but not micro-size range to achieve efficient uptake, significant MHC class I cross-presentation and effective T and B cell responses.

Properties of An Oral Nanoformulation of A Molecularly Dispersed Amphotericin B Comprising A Composite Matrix of Theobroma Oil and Bee'S Wax.

An amphotericin B-containing (AmB) solid lipid nanoparticulate drug delivery system intended for oral administration, comprised of bee’s wax and theobroma oil as lipid components was formulated with the aim to ascertain the location of AmB within the lipid matrix: (a) a homogenous matrix; (b) a drug-enriched shell; or (c) a drug enriched core. Both the drug-loaded and drug-free nanoparticles were spherical with AmB contributing to an increase in both the z-average diameter (169 ± 1 to 222 ± 2 nm) and zeta potential (40.8 ± 0.9 to 50.3 ± 1.0 mV) of the nanoparticles. A maximum encapsulation efficiency of 21.4% ± 3.0%, corresponding to 10.7 ± 0.4 mg encapsulated AmB within the lipid matrix was observed. Surface analysis and electron microscopic imaging indicated that AmB was dispersed uniformly within the lipid matrix (option (a) above) and, therefore, this is the most suitable of the three models with regard to modeling the propensity for uptake by epithelia and release of AmB in lymph.

Nanoemulsions as an effective medium for encapsulation and stabilization of cholesterol/β-cyclodextrin inclusion complex.

Inclusion complex formation between β-cyclodextrin (β-CD) and suitable guest molecules such as cholesterol (Ch) has regularly been exploited to design self-assembled structures. In the present study an effective nanoemulsion medium (lecithin/Tween 80/ethyl oleate/water) was selected for solubilizing and stabilizing Ch and Ch/β-CD inclusion complex. Phase solubility, spectroscopic, thermodynamic, Z-average diameter and morphological analyses were conducted. Phase solubility data analysis demonstrated an increase in Ch solubility at low β-CD concentrations (0.01-0.35 mmol L(-1) ). Transmission electron microscopy and Z-average diameter data indicated the spherical nature of the droplets and confirmed the formation of nanoemulsions with an average size of less than 50 nm. The negative value of ΔG obtained during analysis further indicated that the binding was spontaneous in nature. Primarily, this research demonstrates the use of nanoemulsions as a medium in food matrices, instead of water, for hosting Ch in β-CD.

In Vitro Liberation of Indomethacin from Chitosan Gels Containing Microemulsion in Different Dissolution Mediums

The objective of this research is to outline the liberation of indomethacin from different chitosan gels containing O/W microemulsion. The influence of surfactant, sodium lauryl sulfate, in two concentrations (0.5% and 0.75%, w/w) was determined in dissolution medium on the release of indomethacin, which was used as poor water-soluble model drug. Chitosan gels were prepared in four different concentrations of chitosan-1%, 1.5%, 2%, and 3% (w/w). Microemulsion enhanced the liberation of the indomethacin from chitosan gels into all dissolution mediums. Adding the surfactant into phosphate-buffered saline decreased the amount of liberated indomethacin from microemulsion, gel mixture, but increased the drug liberation from pure chitosan gels. It was detected that with the increased concentration of chitosan in the samples, the amount of indomethacin liberated (p < 0.05) also increased. A conclusion was drawn that the liberation of indomethacin from chitosan gels was influenced by increased pH of the samples. The high viscosity induced a higher release of indomethacin from 3% (w/w) chitosan hydrogel at pH 5.8 as compared with 3% (w/w) chitosan hydrogel at pH 3.8. The highest percentage of released indomethacin was determined when a mixture of microemulsion gel with higher chitosan content was used.

Surfactant Assisted Synthesis of Homogeneous Calcium Based CO2 Sorbent at Room Temperature

Calcium oxide (CaO) sorbents have been recently used for removal of CO2 gases in fossil fuel-fired power plant. However, there are some limitations of CaO in CO2 capturing such as rapid loss of activity during the capture cycles, which is a result of sintering, attrition, and consequent elutriation. Therefore, this paper has demonstrated a novel synthesis method to produce CaO at room temperature to avoid abovementioned drawbacks. In addition, introduction of ionic surfactant of sodium dodecyl sulfate to the CaO formation solution has shown a positive result of formation of homogeneous spherical particle with a mean Z-average diameter of 345.2 nm and polydispersion index (PDI) of 0.335 by dynamical light scattering measurement. Subjected to a high calcination temperature of 1200oC, developed CaO is able to maintain a CO2 uptake capacity of 0.1025 gCO2/gsorbent under 30 minutes of carbonation time. Despite its lower CO2 uptake capacity compared to maximum theoretical limit of 0.78 gCO2/gsorbent, CaO particles is able to withstand a high calcination temperature of 1200oC and reported a particle size distribution ranged from 0.4 - 1.2 µm after calcination which is just slightly larger than fresh developed CaO. Given that such small narrow distributed size of CaO, developed CaO at room temperature is good for packed-bed reactor in calcium looping processes and more studies are required to find a suitable support for fluidized bed reactor type. This successful synthesis story of CaO particle at room temperature has unraveled the possibility to develop nanosized CaO at room temperature in order to achieve high CO2 uptake capacity while enjoying its superior thermal stability over multiple carbonation/calcination cycles.

Laronidase-functionalized multiple-wall lipid-core nanocapsules: promising formulation for a more effective treatment of mucopolysaccharidosis type I.

Mucopolysaccharidosis I is a genetic disorder caused by alpha-L-iduronidase deficiency. Its primary treatment is enzyme replacement therapy (ERT), which has limitations such as a high cost and a need for repeated infusions over the patient's lifetime. Considering that nanotechnological approaches may enhance enzyme delivery to organs and can reduce the dosage thereby enhancing ERT efficiency and/or reducing its cost, we synthesized laronidase surface-functionalized lipid-core nanocapsules (L-MLNC). L-MLNCs were synthesized by using a metal complex. Size distributions were evaluated by laser diffraction and dynamic light scattering. The kinetic properties, cytotoxicity, cell uptake mechanisms, clearance profile and biodistribution were evaluated. Size distributions showed a D[4,3] of 134 nm and a z-average diameter of 71 nm. L-MLNC enhanced the Vmax and Kcat in comparison with laronidase. L-MLNC is not cytotoxic, and nanocapsule uptake by active transport is not only mediated by mannose-6-phosphate receptors. The clearance profile is better for L-MLNC than for laronidase. A biodistribution analysis showed enhanced enzyme activity in different organs within 4 h and 24 h for L-MLNC. The use of lipid-core nanocapsules as building blocks to synthesize surface-functionalized nanocapsules represents a new platform for producing decorated soft nanoparticles that are able to modify drug biodistribution.

Nanoencapsulation of tacrolimus in lipid-core nanocapsules showed similar immunosuppressive activity after oral and intraperitoneal administrations.

Tacrolimus is widely used in the prophylaxis of solid-organ transplant rejection. Several studies have reported that tacrolimus has variable and poor bioavailability after oral administration, apart from adverse effects such as gastrointestinal disorders, hyperglycemia, nephro- and neurotoxicity. The aim of this work was to encapsulate tacrolimus (TAC) in lipid-core nanocapsules (LNC) as an oral strategy to deliver the drug. To validate our hypothesis, the pharmacodynamic effect of TAC-LNC was determined after oral and intraperitoneal (i.p.) administrations to mice. TAC-LNC had z-average diameter of 210 nm (unimodal), and 99.5% of encapsulation efficiency. In vitro sustained release was determined for TAC-LNC fitting an anomalous transport mechanism (n = 0.8). TAC-LNC demonstrated higher immunosuppressive activity after oral and i.p. administrations, when compared to the drug solution. TAC-LNC administered at 6.0 mg kg(-1) day(-1) showed equivalent percent reduction in lymphocyte when both routes of administration were used. After oral administration, drug nanoencapsulation allows reducing the dose by at least 40%. Furthermore, the nanoencapsulation of TAC in lipid-core nanocapsules showed pharmacodynamic effect similar for the oral and the i.p. routes. In conclusion, the lipid-core nanocapsules were able to improve the TAC deliver across the oral absorption barrier.