Zein nanoparticles for oral folic acid delivery

The aim of this work was to prepare and evaluate the capability of zein nanoparticles for oral drug delivery. More particularly, in this work, the ability of these nanoparticles to improve the oral bioavailability of folic acid is reported. The nanoparticles were prepared by a desolvation process, followed by purification via ultrafiltration and drying in a spray-drier apparatus. The resulting nanoparticles displayed a mean size close to 200 nm with negative zeta potential and a payload of 54 μg folic acid per mg nanoparticle. From the in vitro release studies, it was observed that folic acid was only released from nanoparticles in simulated intestinal conditions. In vivo biodistribution studies,with radiolabelled or fluorescently marked nanoparticles, revealed that nanoparticles remained within the gut and were capable of interacting with the protective mucus layer of the jejunum. For the pharmacokinetic study, folic acid was orally administered to rats as a single dose of 1 mg/kg.The relatively oral bioavailability of folic acid, when encapsulated in zein nanoparticles, was around 70%: two-times higher than the value obtained with an aqueous solution of the vitamin. This fact might be explained by the mucoadhesive properties of these nanoparticles

Casein nanoparticles as carriers for the oral delivery of folic acid

Alimentary proteins can be viewed as an adequate material for the preparation of nanoparticles and microparticles. They offer several advantages such as their digestibility, price and a good capability to interact with a wide variety of compounds and nutrients. The aim of this work was to prepare and characterize casein nanoparticles for the oral delivery of folic acid. These nanoparticles were prepared by a coacervation process, stabilized with either lysine or arginine and, finally, dried by spray‐drying. For some batches, the effect of a supplementary treatment of nanoparticles (before drying) with hydrodynamic high pressure on the properties of the resulting carriers was also evaluated. The resulting nanoparticles displayed a mean size close to 150 nm and a folic acid content of around 25 mg per mg nanoparticle. From the in vitro release studies, it was observed that casein nanoparticles acted as gastro‐resistant devices and, thus, folic acid was only released under simulated intestinal conditions. For the pharmacokinetic study, folic acid was orally administered to laboratory animals as a single dose of 1 mg/kg. Animals treated with folic acidloaded casein nanoparticles displayed significantly higher serum levels than those observed in animals receiving an aqueous solution of the vitamin. As a consequence the oral bioavailability of folic acid when administered in casein nanoparticles was calculated to be around 52%, a 50% higher than with the traditional aqueous solution. Unfortunately, the treatment of casein nanoparticles by hydrodynamic high pressure modified neither the release profile of the vitamin nor its oral bioavailability

Encapsulation of Lactobacillus plantarum in casein-chitosan microparticles facilitates the arrival to the colon and develops an immunomodulatory effect

The current work describes the capability of casein-chitosan microparticles to encapsulate Lactobacillus plantarum (CECT 220 and WCFS1 strains) and evaluates their ability to target the distal areas of the gut and to stimulate the immune system. Microparticles were prepared by complex coacervation, between sodium caseinate and chitosan in an aqueous suspension of the bacteria, and dried by spray-drying. In order to increase the survival rate of the loaded bacteria, microparticles were cross-linked with one of the following cross-linkers: tripolyphosphate, calcium salts or vanillin. Overall, microparticles displayed a mean size of about 7.5 μm with a bacteria loading of about 11 Log CFU/g, when cross-linked with vanillin (MP-LP-V). For conventional microparticles, the payload was 10.12 Log CFU/g. The storage stability study at 25 ◦C/60% RH, MP-LP-V offered the highest degree of protection without signif- icant modification of the payload in 260 days. Compared with control (aqueous suspension of bacteria), MP-LP-V also displayed a significantly higher degree of protection against probiotic inactivation in simulated gastric and intestinal fluids. In vivo results evidenced that microparticles, orally administered to rats, were able to reach the distal ileum and colon in about 4 h post-administration. Additionally, the effect of the daily administration of 107 CFU/mouse of MP-LP-V, for 3 weeks, induced an immunomodulatory effect characterized by an important enhancement of Th1 and Th17 responses. In conclusion, these microparticles seem to be a promising strategy for increasing survival and efficacy of probiotics, allowing the formulation of cost-effective and more stable and effective probiotic-based nutraceuticals

Optimization of maghemite-loaded PLGA nanospheres for biomedical applications

Magnetic nanoparticles have been proposed as interesting tools for biomedical purposes. One of their promising utilization is the MRI in which magnetic substances like maghemite are used in a nanometric size and encapsulated within locally biodegradable nanoparticles. In this work, maghemite has been obtained by a modified sol-gel method and encapsulated in polymer-based nanospheres. The nanospheres have been prepared by single emulsion evaporation method. The different parameters influencing the size, polydispersity index and zeta potential surface of nanospheres were investigated. The size of nanospheres was found to increase as the concentration of PLGA increases, but lower sizes were obtained for 3 min of sonication time and surfactant concentration of 1%. Zeta potential response of magnetic nanospheres towards pH variation was similar to that of maghemite-free nanospheres confirming the encapsulation of maghemite within PLGA nanospheres. The maghemite entrapment efficiency and maghemite content for nanospheres are 12% and 0.59% w/w respectively

Protein nanoparticles for oral delivery of bioactives

Food grade proteins can be considered as adequate materials for the preparation of nanoparticles and microparticles. They offer several advantages such as their digestibility, low price and good capability to interact with a wide variety of compounds and nutrients. The aim of this work was to prepare, characterize and evaluate casein and zein nanoparticles for the oral delivery of bioactives. In this order, casein and zein nanoparticles were prepared by a coacervation and desolvation process respectively, followed by purification, concentration and finally dried by spray-drying. The resulting nanoparticles displayed a mean size between 150-300 nm with negative zeta potential. Biodistribution studies in rats showed mucopenetrating abilities for casein nanoparticles and mucus-adhesion properties for zein ones in the proximal jejunum of the rats. Folic acid, resveratrol and quercetin were selected as bioactives and encapsulated into both kind of nanoparticles with encapsulation efficiencies between 50-80%. Casein and zein nanoparticles containing folic acid, resveratrol or quercetin orally administered to male wistar rats displayed in all cases higher drug levels in plasma for at least 24 hours, with longer residence time for zein nanoparticles. This resulted in an increase in the oral bioavailability of the bioactives up to 30-70%. Moreover, the combination of these casein and zein nanoparticles encapsulating quercetin with a P-gP inhibitor, such as 2-hydroxypropyl-b-cyclodextrin (HP-β-CD), was a more effective strategy to increase the oral bioavailability of the active. Besides, the developed zein nanoparticles containing quercetin and resveratrol were evaluated in a LPS endotoxic mice model. Results showed that animals pre-treated with nanoparticles were able to diminish the endotoxic symptoms induced in mice by the intraperitoneal administration of LPS compared to the flavonoids on daily basics. In addition, serum TNF-α also significantly decreased in those animals receiving quercetin encapsulated in zein nanoparticles combined with HP-β-CD. In conclusion, these casein and zein nanocarriers appear to be promising systems for the increase the oral bioavailability of different bioactives

Zein based-nanoparticles improve the oral bioavailability of resveratrol and its anti-inflammatory effects in a mouse model of endotoxic shock

Resveratrol offers pleiotropic health beneficial effects including its reported capability to inhibit lipopolysaccharide (LPS) induced cytokine production. The aim of this work was to prepare, characterize and evaluate a resveratrol nanoparticulate formulation based on zein. For this purpose the oral bioavailability of the encapsulated polyphenol as well as its anti-inflammatory effect in a mouse model of endotoxic shock were studied. Resveratrol-loaded nanoparticles displayed sizes around 300 nm with a negative zeta potential (- 51 mV) and a polyphenol loading close to 80 μg/mg. In vitro, the release of resveratrol from the nanoparticles was found to be pH-independent and adjusted well to the Peppas-Salin kinetic model, suggesting a mechanism based on the combination between diffusion and erosion of the nanoparticle matrix. Pharmacokinetic studies demonstrated that zein-based nanoparticles provided high and prolonged plasma levels of the polyphenol for at least 48 h. The oral bioavailability of resveratrol when administered in these nanoparticles increased up to 50% (20-fold higher than for the control solution of the polyphenol). Furthermore, nanoparticles administered daily for 7 days at 15 mg/kg, were able to diminish the endotoxic symptoms induced in mouse by the ip administration of LPS (i.e. hypothermia, piloerection and stillness). In addition, serum TNF-α levels were slightly lower (about 15%) of those observed for the control

Zein nanoparticles for oral folic acid delivery

The aim of this work was to prepare and evaluate the capability of zein nanoparticles for oral drug delivery. More particularly, in this work, the ability of these nanoparticles to improve the oral bioavailability of folic acid is reported. The nanoparticles were prepared by a desolvation process, followed by purification via ultrafiltration and drying in a spray-drier apparatus. The resulting nanoparticles displayed a mean size close to 200 nm with negative zeta potential and a payload of 54 μg folic acid per mg nanoparticle. From the in vitro release studies, it was observed that folic acid was only released from nanoparticles in simulated intestinal conditions. In vivo biodistribution studies,with radiolabelled or fluorescently marked nanoparticles, revealed that nanoparticles remained within the gut and were capable of interacting with the protective mucus layer of the jejunum. For the pharmacokinetic study, folic acid was orally administered to rats as a single dose of 1 mg/kg.The relatively oral bioavailability of folic acid, when encapsulated in zein nanoparticles, was around 70%: two-times higher than the value obtained with an aqueous solution of the vitamin. This fact might be explained by the mucoadhesive properties of these nanoparticles

Casein nanoparticles as carriers for the oral delivery of folic acid

Alimentary proteins can be viewed as an adequate material for the preparation of nanoparticles and microparticles. They offer several advantages such as their digestibility, price and a good capability to interact with a wide variety of compounds and nutrients. The aim of this work was to prepare and characterize casein nanoparticles for the oral delivery of folic acid. These nanoparticles were prepared by a coacervation process, stabilized with either lysine or arginine and, finally, dried by spray‐drying. For some batches, the effect of a supplementary treatment of nanoparticles (before drying) with hydrodynamic high pressure on the properties of the resulting carriers was also evaluated. The resulting nanoparticles displayed a mean size close to 150 nm and a folic acid content of around 25 mg per mg nanoparticle. From the in vitro release studies, it was observed that casein nanoparticles acted as gastro‐resistant devices and, thus, folic acid was only released under simulated intestinal conditions. For the pharmacokinetic study, folic acid was orally administered to laboratory animals as a single dose of 1 mg/kg. Animals treated with folic acidloaded casein nanoparticles displayed significantly higher serum levels than those observed in animals receiving an aqueous solution of the vitamin. As a consequence the oral bioavailability of folic acid when administered in casein nanoparticles was calculated to be around 52%, a 50% higher than with the traditional aqueous solution. Unfortunately, the treatment of casein nanoparticles by hydrodynamic high pressure modified neither the release profile of the vitamin nor its oral bioavailability

Increased oral bioavailability of resveratrol by its encapsulation in casein nanoparticles

Resveratrol is a naturally occurring polyphenol that provides several health benefits including cardioprotection and cancer prevention. However, its biological activity is limited by a poor bioavailability when taken orally. The aim of this work was to evaluate the capability of casein nanoparticles as oral carriers for resveratrol. Nanoparticles were prepared by a coacervation process, purified and dried by spray-drying. The mean size of nanoparticles was around 200 nm with a resveratrol payload close to 30 µg/mg nanoparticle. In vitro studies demonstrated that the resveratrol release from casein nanoparticles was not affected by the pH conditions and followed a zero-order kinetic. When nanoparticles were administered orally to rats, they remained within the gut, displaying an important capability to reach the intestinal epithelium. No evidence of nanoparticle “translocation” were observed. The resveratrol plasma levels were high and sustained for at least 8 h with a similar profile to that observed for the presence of the major metabolite in plasma. The oral bioavailability of resveratrol when loaded in casein nanoparticles was calculated to be 26.5%, 10 times higher than when the polyphenol was administered as oral solution. Finally, a good correlation between in vitro and in vivo data was observed

Increased oral bioavailability of resveratrol by its encapsulation in casein nanoparticles

Resveratrol is a naturally occurring polyphenol that provides several health benefits including cardioprotection and cancer prevention. However, its biological activity is limited by a poor bioavailability when taken orally. The aim of this work was to evaluate the capability of casein nanoparticles as oral carriers for resveratrol. Nanoparticles were prepared by a coacervation process, purified and dried by spray-drying. The mean size of nanoparticles was around 200 nm with a resveratrol payload close to 30 µg/mg nanoparticle. In vitro studies demonstrated that the resveratrol release from casein nanoparticles was not affected by the pH conditions and followed a zero-order kinetic. When nanoparticles were administered orally to rats, they remained within the gut, displaying an important capability to reach the intestinal epithelium. No evidence of nanoparticle “translocation” were observed. The resveratrol plasma levels were high and sustained for at least 8 h with a similar profile to that observed for the presence of the major metabolite in plasma. The oral bioavailability of resveratrol when loaded in casein nanoparticles was calculated to be 26.5%, 10 times higher than when the polyphenol was administered as oral solution. Finally, a good correlation between in vitro and in vivo data was observed