Polyethylene Glycol-Stabilized Zein Nanoparticles Containing Gallic Acid.

Research background: Gallic acid is a polyphenol with antioxidant and antitumor activities; however, its use as a nutraceutical or drug is hindered by its low bioavailability. Zein is a natural protein found in corn and has been applied as nanoparticle drug carrier. In this study, zein nanoparticles were obtained and stabilized with polyethylene glycol (PEG) as gallic acid carriers. Experimental approach: Nanoparticles were obtained by the liquid-liquid method and characterized in terms of mean size, polydispersity index, zeta potential, morphology, solid-state interactions and encapsulation efficiency/drug loading. The stability of nanoparticles was evaluated in simulated gastrointestinal fluids and food simulants, and the antioxidant activity was determined by the scavenging of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. Results and conclusions: Zein nanoparticles containing gallic acid were obtained and stabilized only in the presence of PEG. Under optimal conditions, nanoparticles with mean size <200 nm, low polydispersity index (<0.25) and negative zeta potential (-20 mV) were obtained. The gallic acid encapsulation efficiency was about 40%, loading about 5%, and it was encapsulated in an amorphous state. Fourier transform infrared spectroscopy (FTIR) did not identify chemical interactions after gallic acid nanoencapsulation. Zein nanoparticles were more prone to release the gallic acid in gastric than intestinal simulated medium; however, more than 50% of drug content was protected from premature release. In food simulants, the gallic acid release from nanoparticles was prolonged and sustained. Moreover, the nanoencapsulation did not reduce the antioxidant activity of gallic acid. Novelty and scientific contribution: The results show the importance of PEG in the formation and its effect on the properties of zein nanoparticles obtained by the liquid-liquid dispersion method. This study indicates that PEG-stabilized zein nanoparticles are potential carriers for oral intake of gallic acid, preserving its antioxidant properties and enabling its use in the pharmaceutical and food industries.

Intranasal administration of perillyl alcohol-loaded nanoemulsion and pharmacokinetic study of its metabolite perillic acid in plasma and brain of rats using ultra-performance liquid chromatography/tandem mass spectrometry.

Perillyl alcohol (POH) is a monocyclic terpene that has strong antitumor activity. Brain tumors are particularly difficult to treat with therapeutic agents, and clinical trials have shown their low tolerance through oral administration. We proposed the entrapment of POH into an oil-in-water chitosan nanoemulsion aiming its intranasal administration for brain targeting. An ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitation of total metabolite perillic acid (PA) in plasma and brain of rats. The rat samples containing the metabolite were treated by liquid-liquid extraction with acetonitrile. The mobile phase was 0.1% formic acid in water (solvent A) and 0.1% formic acid in methanol (solvent B), at a flow rate of 0.3 mL min-1 in gradient elution. The chromatography was run for 10 min, and analytical curves were built in acetonitrile, plasma, and brain. The PA was detected in positive ion mode with multiple reaction monitoring. The method has shown high selectivity, sensitivity, and throughput. The low quantification limits of 162, 178, and 121 ng mL-1 for acetonitrile, brain, and plasma, respectively, indicate a good detectability of the method. The repeatability and precision observed were within the limits recommended in the literature. The accuracy of the method was verified through high recovery rates (106-118%). The validated method was successfully applied to the pharmacokinetic study of the metabolite PA after the intranasal administration of free or POH-loaded nanoemulsion in rats. The results showed that chitosan nanoemulsion improved the plasma and brain bioavailability of POH, representing a promising alternative to free POH treatment.

Antifungal Activity of Chitosan-Coated Poly(lactic-co-glycolic) Acid Nanoparticles Containing Amphotericin B.

Amphotericin B (AmB) is one of the most used drugs for the treatment of systemic fungal infections; however, the treatment causes several toxic manifestations, including nephrotoxicity and hemolytic anemia. Chitosan-coated poly(lactide-co-glycolide) (PLGA) nanoparticles containing AmB were developed with the aim to decrease AmB toxicity and propose the oral route for AmB delivery. In this work, the antifungal efficacy of chitosan-coated PLGA nanoparticles containing AmB was evaluated in 20 strains of fungus isolates from patients with vulvovaginal candidiasis (01 Candida glabrata and 03 Candida albicans), bloodstream infections (04 C. albicans and 01 C. tropicalis) and patients with urinary tract infection (04 Candida albicans, 02 Trichosporon asahii, 01 C. guilhermondii, 03 C. glabrata) and 01 Candida albicans ATCC 90028. Moreover, the cytotoxicity over erythrocytes was evaluated. The single-emulsion solvent evaporation method was suitable for obtaining chitosan-coated PGLA nanoparticles containing AmB. Nanoparticles were spherical in shape, presented mean particle size about 460 nm, positive zeta potential and encapsulation efficiency of 42%. Moreover, nanoparticles prolonged the AmB release. All the strains were susceptible to plain AmB and nanostructured AmB, according to EUCAST breakpoint version 8.1 (resistant > 1 µg/mL), using broth microdilution method. In C. albicans (urine, blood, and vulvovaginal secretion isolates, and 1 ATCC), the MIC value of AmB-loaded nanoparticles varied from 0.25 to 0.5 µg/mL and EUCAST varied from 0.03 to 0.5 µg/mL. In urine and vulvovaginal secretion isolates of C. glabrata, the MIC value of AmB-loaded nanoparticles varied from 0.25 to 0.5 µg/mL and EUCAST varied from 0.03 to 0.015 µg/mL. In urine isolates of C. guilhermondii, the MIC value of AmB-loaded nanoparticles was 0.12 µg/mL and EUCAST was 0.06 µg/mL. In blood isolates of C. tropicalis, the MIC value of AmB-loaded nanoparticles was 0.5 µg/mL and EUCAST was 0.25 µg/mL. Finally, in urine isolates of T asahii, the MIC value of AmB-loaded nanoparticles was 1 µg/mL and EUCAST varied from 0.5 to 1 µg/mL. In the cytotoxicity assay, plain AmB was highly hemolytic (100% in 24 h) while AmB-loaded chitosan/PLGA nanoparticles presented negligible hemolysis.

Bovine serum albumin nanoparticles improve the antitumour activity of curcumin in a murine melanoma model.

Curcumin is a natural compound presenting important antitumour activity. However, due to its low aqueous solubility, instability at physiological pH, and low oral bioavailability, its clinical use is limited. Bovine serum albumin (BSA) nanoparticles have been used as drug carriers to improve the drug properties. In this work, curcumin-loaded BSA nanoparticles were developed and the in vitro cytotoxicity over murine melanoma cells and the in vivo antitumour activity in a murine melanoma model were assessed. Nanoparticles presented 150 nm, polydispersity index of 0.16, negative zeta potential, and 45% of curcumin encapsulation efficiency. Curcumin release from nanoparticles was slow and diffusion dependent. In the cytotoxicity assay, free curcumin was more efficient than curcumin-loaded nanoparticles, probably due to the prolonged curcumin release from nanoparticles. However, in a murine melanoma model, curcumin-loaded nanoparticles presented higher antitumour efficiency than free curcumin. BSA nanoparticles are efficient curcumin carriers that may have relevant applications in melanoma treatment.

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.

Amphotericin B-loaded polymeric nanoparticles: formulation optimization by factorial design.

In this study, PLGA or PLGA-PEG blend nanoparticles were developed loading amphotericin B (AmB), an antifungal agent broadly used in therapy. A 2(2) × 3(1) factorial experimental design was conducted to indicate an optimal formulation of nanoparticles containing AmB and demonstrate the influence of the interactions of components on the mean particle size and drug encapsulation efficiency. The independent variables analyzed were polymer amount (two levels) and organic phase (three factors in one level). The parameters methanol as cosolvent and higher polymer amount originated from the higher AmB encapsulation, but with the larger particle size. The selected optimized parameters were set as the lower polymer amount and ethyl acetate as cosolvent in organic phase, for both PLGA and PLGA-PEG nanoparticles. These parameters originated from nanoparticles with the size of 189.5 ± 90 nm and 169 ± 6.9 nm and AmB encapsulation efficiency of 94.0 ± 1.3% and 92.8 ± 2.9% for PLGA and PLGA-PEG nanoparticles, respectively. Additionally, these formulations showed a narrow size distribution indicating homogeneity in the particle size. PLGA and PLGA-PEG nanoparticles are potential carrier for AmB delivery and the factorial design presented an important tool in optimizing nanoparticles formulations.

Poly(L-lactide) Nanoparticles Reduce Amphotericin B Cytotoxicity and Maintain Its In Vitro Antifungal Activity.

In this study, poly(L-lactide) (PLA) nanoparticles containing amphotericin B (AmB) were developed, and the in vitro cytotoxicity to human erythrocytes and efficacy on strains of Candida spp. were evaluated. The nanoparticles were prepared using an emulsion/solvent evaporation method and were characterized with respect to size, size distribution, AmB encapsulation efficiency, AmB state of aggregation, and AmB in vitro release profile. The mean particle size was 225 nm, and the AmB encapsulation efficiency was over 69%. The AmB in vitro release profile revealed a burst effect within the first 24 h, which released approximately 10% of AmB, followed by a sustained release of approximately 30% of AmB over 30 days. The AmB nanoparticles presented a very low index of hemolysis compared to free AmB, which lysed more than 80% of erythrocytes in the first 2 h of incubation. The AmB-loaded PLA nanoparticles were as effective as free AmB against strains of Candida spp., considering their sustained release profile. Thus, PLA nanoparticles can deliver AmB with reduced toxicity while maintaining its antifungal activity.

Bovine Serum Albumin Nanoparticles Containing Amphotericin B: Characterization, Cytotoxicity and In Vitro Antifungal Evaluation.

In this study, nanoparticles based on bovine serum albumin (BSA) containing amphotericin B (AmB) were obtained by the desolvation method and characterized with respect to size, size distribution, AmB encapsulation efficiency, AmB state of aggregation, and AmB in vitro release profile. After, the effect of nanoparticles on the cytotoxicity of human erythrocytes in vitro and efficacy over strains of Candida spp. were evaluated. The mean particle size was 156 nm and the AmB encapsulation efficiency was over 82%. The in vitro release profile revealed a sustained release of approximately 48% of AmB over 5 days. AmB is present in BSA nanoparticles as monomer. AmB-loaded nanoparticles showed very low index of hemolysis (less than 8%) in 72 h of assay compared to free AmB, which presented 100% of hemolysis in 2 h of incubation. The AmB-loaded BSA nanoparticles were as effective as free AmB against Candida albicans and Candida tropicalis, considering their sustained release profile. Thus, BSA nanoparticles are potential carriers for AmB, reducing its molecular aggregation and prolonging its release, resulting in lower cytotoxicity while maintaining its antifungal activity.

Mitigating amphotericin B cytotoxicity through gliadin-casein nanoparticles: Insights into synthesis, optimization, characterization, in vitro release and cytotoxicity evaluation.

Amphotericin B (AmB) is a widely used antifungal agent; however, its clinical application is limited due to severe side effects and nephrotoxicity associated with parenteral administration. In recent years, there has been growing interest in the utilization of food-grade materials as innovative components for nanotechnology-based drug delivery systems. This study introduces gliadin/casein nanoparticles encapsulating AmB (AmB_GliCas NPs), synthesized via antisolvent precipitation. Formulation was refined using a 24 factorial design, assessing the influence of gliadin and casein concentrations, as well as organic and aqueous phase volumes, on particle size, polydispersity index (PDI), and zeta potential. The optimal composition with 2 % gliadin, 0.5 % casein, and a 1:5 organic-to-aqueous phase ratio, yielded nanoparticles with a 442 nm size, a 0.307 PDI, a -20 mV zeta potential, and 82 % entrapment efficiency. AmB was confirmed to be amorphous within the nanoparticles by X-ray diffraction. These NPs released AmB sustainably over 96 h, primarily in its monomeric form. Moreover, NPs maintained stability in simulated gastrointestinal fluids with minimal drug release and showed significantly lower hemolytic activity and cytotoxicity on Vero cells than free AmB, suggesting their promise for oral AmB delivery.

Oral Delivery of Liraglutide-Loaded Zein/Eudragit-Chitosan Nanoparticles Provides Pharmacokinetic and Glycemic Outcomes Comparable to Its Subcutaneous Injection in Rats.

Liraglutide (LIRA) is a glucagon-like peptide-1 (GLP-1) receptor agonist renowned for its efficacy in treating type 2 diabetes mellitus (T2DM) and is typically administered via subcutaneous injections. Oral delivery, although more desirable for being painless and potentially enhancing patient adherence, is challenged by the peptide's low bioavailability and vulnerability to digestive enzymes. This study aimed to develop LIRA-containing zein-based nanoparticles stabilized with eudragit RS100 and chitosan for oral use (Z-ERS-CS/LIRA). These nanoparticles demonstrated a spherical shape, with a mean diameter of 238.6 nm, a polydispersity index of 0.099, a zeta potential of +40.9 mV, and an encapsulation efficiency of 41%. In vitro release studies indicated a prolonged release, with up to 61% of LIRA released over 24 h. Notably, the nanoparticles showed considerable resistance and stability in simulated gastric and intestinal fluids, suggesting protection from pH and enzymatic degradation. Pharmacokinetic analysis revealed that orally administered Z-ERS-CS/LIRA paralleled the pharmacokinetic profile seen with subcutaneously delivered LIRA. Furthermore, in vivo tests on a diabetic rat model showed that Z-ERS-CS/LIRA significantly controlled glucose levels, comparable to the results observed with free LIRA. The findings underscore Z-ERS-CS/LIRA nanoparticles as a promising approach for oral LIRA delivery in T2DM management.

Effect of the o-methyl catechols apocynin, curcumin and vanillin on the cytotoxicity activity of tamoxifen.

Apocynin (APO), curcumin (CUR) and vanillin (VAN) are o-methyl catechols widely studied due their antioxidant and antitumour properties. The effect of treatment with these o-methyl catechols on tamoxifen (TAM)-induced cytotoxicity in normal and tumour cells was studied. The cytotoxicity of TAM on red blood cells (RBC) was performed by haemoglobin or K(+)release and on polymorphonuclear leukocytes (PMNs) by trypan blue dye exclusion method. Cytotoxic activity was assessed in human chronic myeloid leukemia (K562) cell line by (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide). According the release of haemoglobin and K(+), the CUR showed a decrease in TAM cytotoxicity on RBC; however, in PMN, APO, CUR and VAN showed increased of these cells viability. VAN presented the highest cytotoxicity on K562 cells, followed by APO and CUR. These results point the potential therapeutic value of these o-methyl catechols with TAM, particularly of CUR, which potentiates the cytotoxic effects of TAM on K562 cells and also decreases TAM-associated cytotoxicity on RBC and PMN.

Resveratrol-loaded polymeric nanoparticles: validation of an HPLC-PDA method to determine the drug entrapment and evaluation of its antioxidant activity.

Poly(lactic acid) (PLA) and PLA-poly(ethylene glycol) (PLA-PEG) nanoparticles containing resveratrol (RVT) were developed, and their antioxidant activity was evaluated. An analytical method using high performance liquid chromatography (HPLC)/photodiode array (PDA) detection was also developed and validated for RVT determination in nanoparticles. The mobile phase consisted of methanol : water (51 : 49, v/v) flowed at 0.9 mL/min, and the PDA detector was set at wavelength of 306 nm. The mean diameter of the nanoparticles varied between 180 and 220 nm, and the encapsulation efficiency of RVT ranged from 60% to 88%. The nanoparticles containing RVT were evaluated for their ability to scavenge the radical (2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) (ABTS•⁺). The profile obtained from the PLA nanoparticles containing RVT demonstrated that after 24 h, there was almost no increase in antioxidant activity, which was lower than that of the free RVT and RVT-loaded PLA-PEG nanoparticles. For PLA-PEG nanoparticles, the radical-scavenging activity of RVT was shown to increase with time, and after 48 h, it was similar to that observed with free RVT.

Enhancing Oral Bioavailability and Brain Biodistribution of Perillyl Alcohol Using Nanostructured Lipid Carriers.

Perillyl alcohol (POH), a bioactive monoterpenoid derived from limonene, shows promise as an antitumor agent for brain tumor treatment. However, its limited oral bioavailability and inadequate brain distribution hinder its efficacy. To address these challenges, this study developed nanostructured lipid carriers (NLCs) loaded with POH to improve its brain biodistribution. The NLCs prepared using hot homogenization exhibited an average diameter of 287 nm and a spherical morphology with a polydispersity index of 0.143. High encapsulation efficiency of 99.68% was achieved. X-ray diffraction analyses confirmed the semicrystalline state of POH-loaded NLCs. In vitro release studies demonstrated a biphasic release profile. Stability studies in simulated gastric and intestinal fluids confirmed their ability to withstand pH variations and digestive enzymes. In vivo pharmacokinetic studies in rats revealed significantly enhanced oral bioavailability of POH when encapsulated in the NLCs. Biodistribution studies showed increased POH concentration in brain tissue with NLCs compared with free POH, which was distributed more in non-target tissues such as the liver, lungs, kidneys, and spleen. These findings underscore the potential of NLCs as effective delivery systems for enhancing oral bioavailability and brain biodistribution of POH, providing a potential therapeutic strategy for brain tumor treatment.

Bovine Serum Albumin Nanoparticles Enhanced the Intranasal Bioavailability of Silybin in Rats.

Silybin (SLB), an important flavonoid from silymarin, displays significant hepatoprotective, anticancer, antioxidant, and neuroprotective effects. However, its therapeutic efficacy is limited by its low solubility and bioavailability. To address these challenges, we engineered bovine serum albumin (BSA) nanoparticles (NP) loaded with SLB (BSA-NP/SLB) using the coacervation method. BSA-SLB NP exhibited a spherical shape, a mean size of 197 nm, a polydispersity index of 0.275, a zeta potential of -34 mV, and an entrapment efficiency of 67%. X-ray diffraction analysis indicated amorphization of SLB upon encapsulation. Formulation stability was upheld over 180 days. In vitro release assays demonstrated controlled diffusion-erosion release, with approximately 40% SLB released within 0.5 h and 100% over 12 h. Intranasal administration of BSA-NP/SLB in rats improved SLB bioavailability by fourfold compared to free SLB. These findings highlight the promising potential of intranasally administered BSA-NP/SLB as an alternative approach to enhance SLB bioavailability, paving the way for innovative therapeutic applications.

Nanotechnology-Based Approaches for Voriconazole Delivery Applied to Invasive Fungal Infections.

Invasive fungal infections increase mortality and morbidity rates worldwide. The treatment of these infections is still limited due to the low bioavailability and toxicity, requiring therapeutic monitoring, especially in the most severe cases. Voriconazole is an azole widely used to treat invasive aspergillosis, other hyaline molds, many dematiaceous molds, Candida spp., including those resistant to fluconazole, and for infections caused by endemic mycoses, in addition to those that occur in the central nervous system. However, despite its broad activity, using voriconazole has limitations related to its non-linear pharmacokinetics, leading to supratherapeutic doses and increased toxicity according to individual polymorphisms during its metabolism. In this sense, nanotechnology-based drug delivery systems have successfully improved the physicochemical and biological aspects of different classes of drugs, including antifungals. In this review, we highlighted recent work that has applied nanotechnology to deliver voriconazole. These systems allowed increased permeation and deposition of voriconazole in target tissues from a controlled and sustained release in different routes of administration such as ocular, pulmonary, oral, topical, and parenteral. Thus, nanotechnology application aiming to delivery voriconazole becomes a more effective and safer therapeutic alternative in the treatment of fungal infections.

Nanoencapsulation and characterization of zidovudine on poly(L-lactide) and poly(L-lactide)-poly(ethylene glycol)-blend nanoparticles.

In this work, the antiretroviral zidovudine was encapsulated on biodegradable poly(L-lactide) (PLA) or poly(L-lactide)-poly(ethylene glycol) (PLA-PEG)-blend nanoparticles by the double-emulsion solvent-evaporation method. The PLA-PEG blend was obtained by the physical mixture of the isolated polymers in organic solvent, whose PEG content ranges from 5 to 50 g in the blends. The physicochemical characteristics of the nanoparticles were evaluated applying particle-size and zeta-potential analyses, scanning electron microscopy, differential scanning calorimetry and Fourier-transform infrared spectroscopy. The release rate of zidovudine from the nanoparticles was investigated as well. The drug encapsulation efficiencies were around 50%, and the mean diameters of the nanoparticles were less than 400 nm. The PEG presence influenced all of the analyzed physicochemical parameters. The amount of drug released increases with the PEG presence in the blend. Therefore, the investigated nanoparticles are very promising carriers for zidovudine.

PHBV/PCL microparticles for controlled release of resveratrol: physicochemical characterization, antioxidant potential, and effect on hemolysis of human erythrocytes.

Microparticles of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) containing resveratrol were successfully prepared by simple emulsion/solvent evaporation. All formulations showed suitable encapsulation efficiency values higher than 80%. PHBV microparticles revealed spherical shape with rough surface and presence of pores. PCL microparticles were spherically shaped with smooth surface. Fourier-transformed infrared spectra demonstrated no chemical bond between resveratrol and polymers. X-ray powder diffraction patterns and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. These PHBV/PCL microparticles delayed the dissolution profile of resveratrol. Release profiles were better fitted to biexponential equation. The hypochlorous-acid-scavenging activity and 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation discoloration assay confirmed that the antioxidant activity of PHBV/PCL microparticles was kept, but was dependent on the microparticle morphology and dissolution profile. Resveratrol-loaded PHBV/PCL microparticles showed no cytotoxic effect on red blood cells.

Ursolic acid-loaded lipid-core nanocapsules reduce damage caused by estrogen deficiency in wound healing.

The skin aging process in women is accelerated due to decreases in serum estrogen levels triggered by the menopause process. Hence, poly(L-lactic acid) lipid-core nanocapsules containing ursolic acid (NPLA-UA) were developed using the interfacial deposition of the preformed polymer methodology as a strategy to reduce damages to the healing process caused by hormonal deficiency in ovariectomized rats. The colloidal suspensions of nanocapsules presented adequate size and morphology (254 and 375 nm), negative zeta potential (-31 and -37 mV), high encapsulation efficiency (99.89 %), and amorphous character. The analyses performed in an in vivo healing trial showed that the treatment with NPLA-UA resulted in faster wound retraction with less inflammatory response. In addition, the angiogenic process was stimulated increased synthesis of dermal collagen occurred. Ursolic acid-loaded, lipid-core nanocapsules are suitable for treating skin changes triggered by decreased estrogen in menopause.

Nanoparticles as a Tool for Broadening Antifungal Activities.

Fungal infections are diseases that are considered neglected although their infection rates have increased worldwide in the last decades. Thus, since the antifungal arsenal is restricted and many strains have shown resistance, new therapeutic alternatives are necessary. Nanoparticles are considered important alternatives to promote drug delivery. In this sense, the objective of the present study was to evaluate the contributions of newly developed nanoparticles to the treatment of fungal infections. Studies have shown that nanoparticles generally improve the biopharmaceutical and pharmacokinetic characteristics of antifungals, which is reflected in a greater pharmacodynamic potential and lower toxicity, as well as the possibility of prolonged action. It also offers the proposition of new routes of administration. Nanotechnology is known to contribute to a new drug delivery system, not only for the control of infectious diseases but for various other diseases as well. In recent years, several studies have emphasized its application in infectious diseases, presenting better alternatives for the treatment of fungal infections.

Chitosan Nanoparticles Potentiate the in vitro and in vivo Effects of Curcumin and other Natural Compounds.

The development of biodegradable nanoparticles is an important tool for the biological transport of chemical compounds. The nanoencapsulation reduces the biopharmaceutical and pharmacokinetic drawbacks of compounds and enhances their biological properties. Naturally occurring polymers such as proteins and polysaccharides have been widely applied in the development of nanostructured systems of several therapeutic agents. Among them is chitosan, a crustacean-carapace-chitin derived biopolymer. In addition to its biocompatibility and biodegradability, chitosan is known for its mucoadhesion properties. Chitosan-based nanostructured systems potentiate most of the aspects of the loaded drugs, including cellular transport and other biological effects. The use of chitosan nanoparticles enhances permeation, stability, and bioactivity of natural compounds. In this review, an overview of the main features of chitosan nanoparticles that improved in vitro and in vivo effects of bioactive natural molecules is given, emphasizing the results obtained with curcumin.