Chitosan modified poly (lactic acid) nanoparticles increased the ursolic acid oral bioavailability.

Ursolic acid (UA) is a naturally occurring triterpene that has been investigated for its antitumor activity. However, its lipophilic character hinders its oral bioavailability, and therapeutic application. To overcome these limitations, chitosan (CS) modified poly (lactic acid) (PLA) nanoparticles containing UA were developed, characterized, and had their oral bioavailability assessed. The nanoparticles were prepared by emulsion-solvent evaporation technique and presented a mean diameter of 330 nm, zeta potential of +28 mV, spherical shape and 90% encapsulation efficiency. The analysis of XRD and DSC demonstrated that the nanoencapsulation process induced to UA amorphization. The in vitro release assay demonstrated that 53% of UA was released by diffusion after 144 h, following a second-order release kinetics. In simulated gastrointestinal fluids and mucin interaction tests, CS played an important role in stability and mucoadhesiveness improvement of PLA nanoparticles, respectively. In the presence of erythrocytes, nanoparticles proved their hemocompatibility. In tumor cells, nanoparticles presented lower cytotoxicity than free UA, due to slow UA release. After a single oral dose in rats, CS modified PLA nanoparticles increased the UA absorption, reduced its clearance and elimination, resulting in increased bioavailability. The results show the potential application of these nanoparticles for UA oral delivery for cancer therapy.

Bovine serum albumin-based nanoparticles containing the flavonoid rutin produced by nano spray drying

Rutin is a flavonoid compound obtained from different vegetables and fruits; specifically, it is found in the seeds of buckwheat and in fruit peels, particularly citrus. It is also an important constituent of red wine. Rutin exhibits various biological properties including antiviral, vasoprotective, anti-inflammatory, and anticarcinogenic activities. However, its antioxidant activity is the most well studied. Despite the potential for in vitro applications, rutin presents low oral bioavailability that affects its biological activities. Nanoparticles composed of polymers, protein, or lipids are of great importance in the pharmaceutical and nutraceutical areas due to their physicochemical properties, which improve the pharmacokinetics of the drug which is loaded within. This study presents the production of bovine serum albumin (BSA) nanoparticles containing rutin by nano spray drying. Nanoparticles were characterized in terms of mean particle size, size distribution, morphology, zeta potential, and drug content; as well as their antioxidant activity. The optimized spray-drying conditions produced spherical particles with a mean size of 316 nm, zeta potential of −32 mV, and encapsulation efficiency around 32%. Moreover, when antioxidant activity toward the ABTS+ radical was assayed, nanoencapsulation increased the IC50 of rutin by 2-fold. The nano spray-drying process proved to be suitable for the production of rutin-loaded BSA nanoparticles with potential antioxidant activity.

Preparation, physicochemical characterization and antioxidant activity of diphenyl diselenide-loaded poly(lactic acid) nanoparticles.

In this study, we developed, characterized and evaluated the antioxidant activity of poly (lactic acid) nanoparticles containing diphenyl diselenide (PhSe)2. Nanoparticles were characterized in terms of mean particle size, polydispersity index, zeta potential, encapsulation efficiency, in vitro release profile, physical stability, polymer-drug interactions and thermal properties. Also, the antioxidant activity of nanoparticles on hypochlorous acid (HOCl) was assessed. Nanoparticles presented a mean size of 210nm, had low polydispersity, zeta potential of -24mV, and an encapsulation efficiency over 90%. Differential scanning calorimetry and X-ray diffraction results showed (PhSe)2 is dispersed in PLA matrix in an amorphous state. Lyophilized nanoparticles maintained physical stability over three months, while nanoparticles dispersed in water did not present stability over 7days. In vitro release assay was characterized by a biphasic release pattern with burst effect in 8h followed by a sustained release diffusion governed over 192h. Nanoencapsulation did not alter the antioxidant activity of (PhSe)2 on HOCl. The study concludes these properties of (PhSe)2-loaded nanoparticles can be useful to extend the biological effects of (PhSe)2.

Poly(lactic acid) nanoparticles loaded with ursolic acid: Characterization and in vitro evaluation of radical scavenging activity and cytotoxicity.

The purpose of this study was to develop poly(lactic acid) (PLA) nanoparticles containing ursolic acid (UA) by an emulsification-solvent evaporation technique and evaluate the radical scavenging activity over hypochlorous acid (HOCl) and cytotoxicity over erythrocytes and tumor cells. Nanoparticles were successfully obtained and presented mean size of 246nm with spherical or slightly oval morphology, negative zeta potential and 96% of UA encapsulation efficiency. Analyses of FTIR, XRD and DSC-DTG suggest interaction/complexation of UA with PLA matrix and drug amorphization promoted by nanoencapsulation process. Stability study showed that room temperature was the best condition for nanoparticles storage. The in vitro release study showed UA was released from the polymeric matrix over two constants (α, ß), suggesting a second order kinetics. After 120h of assay, 60% of UA were released by diffusion. In the HOCl scavenging activity, after 72h of assay UA-loaded nanoparticles presented the same efficacy of free drug. In cytotoxicity test over red blood cells, UA-loaded nanoparticles showed less toxicity on cells than free drug. The cytotoxicity assay over melanoma cells line (B16-F10) showed after 72h that nanoparticles were able to reduce the cell viability in 70%. PLA nanoparticles showed be potential carriers for UA maintaining the antioxidant and antitumor activity of the UA and decreasing its cytotoxicity over normal cells.

Bovine Serum Albumin Nanoparticles Containing Quercetin: Characterization and Antioxidant Activity.

Quercetin is a flavonoid reported as anti-allergic, anti-inflammatory, antiplatelet, anti-microbial, antioxidant, antineurodegenerative and antitumoral. However, due to its low water solubility, its efficacy is restricted. Nanotechnology can be an importante tool to improve the quercetin properties and increase its bioavailability. In this study, bovine serum albumin (BSA) nanoparticles containing quercetin were developed by desolvation technique, characterized the mean particle size, polydispersity, zeta potential, encapsulation efficiency, physical state of drug in nanoparticles and drug release profile as well as their antioxidant activity was evaluated. The influence of glutaraldehyde percentage in nanoparticles properties was evaluated and did not influence the nanoparticles parameters. Nanoparticles presented a mean size around 130 nm and encapsulation efficiency around 85%. Results from X-ray diffractometry showed that the crystal of the drug was converted to an amorphous state in polymeric matrix. Quercetin release profile demonstrated a biphasic pattern and after 96 h approximately 18% of drug was released. Kinetic models demonstrated that the quercetin release followed a second-order model and the release was governed by Fickian diffusion. After 96 h, quercetin-loaded nanoparticles were more effective than free quercetin for scanvenger of radical ABTS + and hypochlorous acid. BSA nanoparticles represents potential carriers for improve quercetin properties.