Semi-Mechanistic Pharmacokinetic Modeling of Lipid Core Nanocapsules: Understanding Quetiapine Plasma and Brain Disposition in a Neurodevelopmental Animal Model of Schizophrenia.

This study investigated plasma and brain disposition of quetiapine lipid core nanocapsules (QLNC) in naive and schizophrenic (SCZ-like) rats and developed a semimechanistic model to describe changes in both compartments following administration of the drug in solution (FQ) or nanoencapsulated. QLNC (1 mg/ml) presented 166 ± 39 nm, low polydispersity, and high encapsulation (93.0% ± 1.4%). A model was built using experimental data from total and unbound plasma and unbound brain concentrations obtained by microdialysis after administration of single intravenous bolus dose of FQ or QLNC to naive and SCZ-like rats. A two-compartment model was identifiable both in blood and in brain with a bidirectional drug transport across the blood-brain barrier (CLin and CLout). SCZ-like rats' significant decrease in brain exposure with FQ (decrease in CLin) was reverted by QLNC, showing that nanocarriers govern quetiapine tissue distribution. Model simulations allowed exploring the potential of LNC for brain delivery. SIGNIFICANCE STATEMENT: A population approach was used to simultaneously model total and unbound plasma and unbound brain quetiapine concentrations allowing for quantification of the rate and extent of the drug's brain distribution following administration of both free drug in solution or as nanoformulation to naive and SCZ-like rats. The model-based approach is useful to better understand the possibilities and limitations of this nanoformulation for drug delivering to the brain, opening the opportunity to use this approach to improve SCZ-treatment-limited response rates.

Addition of norbixin microcapsules obtained by spray drying in an isotonic tangerine soft drink as a natural dye.

Annatto seeds (Bixa orellana L.) are a natural source of norbixin, a carotenoid with antioxidant activity and an intense yellow-orange color which is a commonly used food and beverage colorant. However, it is susceptible to environmental factors such as light, oxygen, and temperature. Microencapsulation presents an alternative for improving the bioactive compound's stability. In this study, norbixin microcapsules (MCN) were added to isotonic tangerine soft drinks in a quantity not exceeding food additive regulations. The final concentration was 2.86 ± 0.02 µg norbixin/mL, and according to the CIELab system, the beverage acquired the expected orange tonality. The addition of MCN favorably affects beverage stability during storage under accelerated conditions (heat and light), and the half-life time was more significant (29.71 days) than when non-encapsulated norbixin was used (393.39 min). In conclusion, MCN should be considered as an additive with potential use in processed beverage industries instead of synthetic dyes.

Production of Isotonic, Sterile, and Kinetically Stable Lipid-Core Nanocapsules for Injectable Administration.

Lipid-core nanocapsules (LNC) were designed and prepared as a colloidal system for drug targeting to improve the stability of drugs and allow their controlled release. For parenteral administration, it is necessary to ensure formulation sterility. However, sterilization of nanotechnological devices using an appropriate technique that keeps the supramolecular structure intact remains a challenge. This work aimed to evaluate the effect of autoclaving on the physicochemical characteristics of LNC. Formulations were prepared by the self-assembling method, followed by isotonization and sterilization at varying times and temperatures. The isotonicity was confirmed by determining the freezing temperature, which was -0.51°C. The formulation was broadly characterized, and the diameter of the particles was determined utilizing complementary methods. To evaluate the chemical stability of poly(ε-caprolactone), its molecular weight was determined by size exclusion chromatography. The physicochemical characteristics (average diameter, viscosity, and physical stability) of the formulation were similar before and after adding glycerol and conducting the sterilization at the highest temperature (134°C) and the shorter exposure time (10 min). After autoclaving, the sterility test was performed and showed no detectable microbial growth. Multiple light scattering demonstrated that the formulations were kinetically stable, and the mean diameter was constant for 6 months, corroborating this result. The polymer was chemically stable in the sterilized formulation. Isotonic and sterile LNC aqueous suspensions were produced using glycerol and autoclaving. Briefly, the results open an opportunity to produce an isotonic and sterile LNC aqueous dispersion applicable as nanomedicine for intravenous administration in clinical trials.

Pharmacokinetic Investigation of Quetiapine Transport across Blood-Brain Barrier Mediated by Lipid Core Nanocapsules Using Brain Microdialysis in Rats.

Lipid-core nanocapsules (LCNs) have been proposed as drug carriers to improve brain delivery by modulating drug pharmacokinetics (PK). However, it is not clear whether the LCNs carry the drug through the blood-brain barrier or increase free drug penetration due to changes in the barrier permeability. Quetiapine (QTP) penetration to the brain is mediated by influx transporters and therefore might be reduced by drug transporters inhibitiors as probenecid. The goal of this work was to investigate the role of type-III LCNs on brain penetration of QTP using microdialysis in the presence probenecid. QTP-loaded LCN (QLNC) was successfully obtained with a small particle size (143 ± 6 nm), low polydispersity index (PI < 0.1), and high encapsulation efficiency (95.4 ± 1.82%.). Total and free drug concentration in plasma and free drug concentration in brain were analyzed following i.v. bolus dosing of nonencapsulated drug (FQ) and QLNC formulations alone and in association with probenecid to male Wistar rats. QTP free plasma fraction right after administration of QLNC was smaller than the fraction observed after FQ dosing; however, it increased over time until similar free drug levels were attained, suggesting that type-III LNCs produce a short in vivo sustained release of the drug. The inhibition of influx transporters by PB led to a reduction of free QTP brain penetration, as observed by the reduction of penetration factor from 1.55 ± 0.17 to a value closer to unit (0.94 ± 0.15). However, when the drug was nanoencapsulated, the inhibition of influx transporters had no effect on the brain penetration factor (0.88 ± 0.21 to 0.92 ± 0.13) probably because QTP is loaded into LNC and not available to interact with transporters. Taken together, these results suggest that LNC type-III carried QTP in the bloodstream and delivered the drug to the brain.

Hydrogel containing adapalene- and dapsone-loaded lipid-core nanocapsules for cutaneous application: development, characterization, in vitro irritation and permeation studies.

Lipid-core polymeric nanocapsule suspensions containing adapalene and dapsone (AD-LCNC) were developed and incorporated in a Carbopol 940® hydrogel (AD-LCNC HG). A nanoemulsion (AD-NE), similarly prepared but omitting the polymer, was developed and also incorporated in a Carbopol 940® hydrogel (AD-NE HG) to evaluate the polymer effect. Physicochemical characteristics were evaluated. AD-LCNC suspensions containing 0.07% of dapsone and 0.025% of adapalene presented an average size of 194.9 ± 0.42 nm, zeta potential of -15 ± 1.2 mV and polydispersity index of 0.12 ± 0.02, using electrophoretic light scattering (n = 3). The granulometric profiles showed unimodal size distributions for AD-LCNC suspensions, demonstrating that no microscopic population is present in the formulation. No instability phenomena were observed by multiple light-scattering analysis. Photomicrographs obtained by TEM showed homogeneous- and spherical-shaped particles. The encapsulation efficiency was 99.99% for dapsone and 100% for adapalene. The pH values for AD-LCNC suspensions were 5.1 and 7.6 for AD-LCNC HG. Formulations were classified as nonirritant in the HET-CAM test. Rheological analysis demonstrated a non-Newtonian pseudoplastic profile. The in vitro skin permeation studies showed a higher amount of adapalene in epidermis (130.52 ± 25.72 ng/mg) and dermis (4.66 ± 2.5 ng/mg) for AD-NE HG. The AD-LCNC HG presented higher amount of dapsone in both the skin layers (73.91 ± 21.64 ng/mg in epidermis and 4.08 ± 0.85 ng/mg in dermis). The assay showed significant difference between AD-LCNC HG and AD-NE HG (p < 0.05), and drug was not found in the receptor medium.

Pharmacokinetic/pharmacodynamic modeling of cortical dopamine concentrations after quetiapine lipid core nanocapsules administration to schizophrenia phenotyped rats.

Schizophrenia (SCZ) response to pharmacological treatment is highly variable. Quetiapine (QTP) administered as QTP lipid core nanocapsules (QLNC) has been shown to modulate drug delivery to the brain of SCZ phenotyped rats (SPR). In the present study, we describe the brain concentration-effect relationship after administrations of QTP as a solution or QLNC to SPR and naïve animals. A semimechanistic pharmacokinetic (PK) model describing free QTP concentrations in the brain was linked to a pharmacodynamic (PD) model to correlate the drug kinetics to changes in dopamine (DA) medial prefrontal cortex extracellular concentrations determined by intracerebral microdialysis. Different structural models were investigated to fit DA concentrations after QTP dosing, and the final model describes the synthesis, release, and elimination of DA using a pool compartment. The results show that nanoparticles increase QTP brain concentrations and DA peak after drug dosing to SPR. To the best of our knowledge, this is the first study that combines microdialysis and PK/PD modeling in a neurodevelopmental model of SCZ to investigate how a nanocarrier can modulate drug PK and PD, contributing to the development of new treatment strategies for SCZ.

Thermosensitive and mucoadhesive hydrogel containing curcumin-loaded lipid-core nanocapsules coated with chitosan for the treatment of oral squamous cell carcinoma.

Buccal drug administration may be chosen as a medication route to treat various diseases for local or systemic effects. This study proposes the development of a thermosensitive hydrogel containing curcumin-loaded lipid-core nanocapsules coated with chitosan to increase mucoadhesion, circumventing several limitations of this route of administration. Hydroxypropylmethylcellulose and Poloxamer® 407 were incorporated for hydrogel production. Physicochemical characterization parameters, such as particle size distribution, mean diameter, polydispersity index, zeta potential, and morphology, were analyzed. Spherical homogeneous particles were obtained with average diameter, of 173 ± 22 nm for LNCc (curcumin lipid-core nanocapsules) and 179 ± 48 nm for CLNCc (chitosan-curcumin lipid-core nanocapsules). A PDI equal to 0.09 ± 0.02 for LNCc and 0.26 ± 0.01 for CLNCc confirmed homogeneity. Tensile analysis and washability test on porcine buccal mucosa indicated higher mucoadhesion for hydrogels in comparison to the nanocapsules in suspension, remaining on the mucous membrane up to 8 h (10.92 ± 3.95 µg of curcumin washed for H-LNCc and 28.41 ± 24.47 µg for H-CLNCc) versus the latter, which remained washed on the membrane for 90 min only (62.60 ± 4.72 µg for LNCc and 52.08 ± 1.63 µg for CLNCc). The irritant potential (IR) of the formulations was evaluated by the hen's egg chorioallantoic membrane test (HET-CAM), with no irritation phenomena observed. Formulations were tested for their efficacy in an in vitro model against oral squamous cancer cell line, showing a significant reduction in cell viability on all tested groups. These findings demonstrated that the proposed nanosystem is mucoadhesive and has potential to deliver buccal treatments.

Characterization and in vivo toxicological evaluation of multi-walled carbon nanotubes: a low-dose repeated intratracheal administration study.

This study characterized and investigated the toxicity of two multi-walled carbon nanotubes (MWCNT) NM-401 and NM-403 at 60 and 180 µg after four repeated intratracheal instillations; follow-up times were 3, 7, 30, and 90 days after the last instillation. NM-401 was needle-like, long, and thick, while NM-403 was entangled, short, and thin. Both MWCNT types induced transient pulmonary and systemic alterations in renal function and oxidative lipid damage markers in recent times. Animals showed general toxicity in the immediate times after exposures, in addition to increased pulmonary LDH release at day 3. In further times, decreased liver and kidney relative weights were noted at higher MWCNT doses. Lung histological damages included pulmonary fibrosis, for both MWCNT types, similarly to asbestos; single liver and kidney histological alterations were present. Repeated instillations led to persistent pulmonary damage at low doses, and possibly the extrapulmonary effects may be associated with the consecutive exposures.

Toltrazuril-Loaded Polymeric Nanocapsules as a Promising Approach for the Preventive Control of Coccidiosis in Poultry.

Coccidiosis is a disease caused by intracellular protozoan parasites of the genus Eimeria that affect the intestinal tract of poultry. However, strain resistance and drug residue in the carcass have drawn the attention of the productive sector. The nanotechnology can improve the biological effect of drugs, reducing of administered doses and toxic effects. Due to this, toltrazuril-load polymeric nanoparticles based on Eudragit® S100 (NCt) or poly-ε-caprolactone (LNCt) were developed to prevent coccidiosis in broilers. Nanoformulations were produced and showed homogeneous particle diameter distribution in the nanometer range (z-average and D (4.3) < 200 nm), negative zeta potential (<-8.93 mV), drug content ~100%, and encapsulation efficiency >90%. Cell viability assays using avian fibroblasts showed that LNCt presented no relevant toxicity up to 72 h. LNCt was then prophylactically administrated to chicken followed by challenge with Eimeria oocysts. The evaluation of the small intestine and cecum showed that the treatment with LNCt (3.5 mg/kg/day) in drinking water reduced the lesion scores and oocysts excretion, similar to the reference medicine containing toltrazuril (Baycox®, 7 mg/kg/day). The current study shows the potential protective use of nanoencapsulating anticoccidial drugs as a promising approach for the control of coccidiosis in poultry.

Nanoformulation Shows Cytotoxicity against Glioblastoma Cell Lines and Antiangiogenic Activity in Chicken Chorioallantoic Membrane.

Glioblastoma (GB) is a histological and genetically heterogeneous brain tumor that is highly proliferative and vascularized. The prognosis is poor with currently available treatment. In this study, we evaluated the cytotoxicity and antiangiogenic activity of doxorubicin-loaded-chitosan-coated-arginylglycylaspartic acid-functionalized-poly(ε-caprolactone)-alpha bisabolol-LNC (AB-DOX-LNC-L-C-RGD). The nanoformulation was prepared by self-assembling followed by interfacial reactions, physicochemically characterized and evaluated in vitro against GB cell lines (U87MG and U138MG) and in vivo using the chicken chorioallantoic membrane assay (CAM). Spherical shape nanocapsules had a hydrodynamic mean diameter of 138 nm, zeta potential of +13.4 mV, doxorubicin encapsulation of 65%, and RGD conjugation of 92%. After 24 h of treatment (U87MG and U138MG), the median inhibition concentrations (IC50) were 520 and 490 nmol L-1 doxorubicin-equivalent concentrations, respectively. The treatment induced antiproliferative activity with S-phase cell-cycle arrest and apoptosis in the GB cells. Furthermore, after 48 h of exposure, evaluation of antiangiogenic activity (CAM) showed that the relative vessel growth following treatment with the nanocapsules was 5.4 times lower than that with the control treatment. The results support the therapeutic potential of the nanoformulation against GB and, thereby, pave the way for future preclinical studies.

Quetiapine lipid core nanocapsules restore prepulse inhibition deficits in a neurodevelopmental model of schizophrenia in male and female rats.

Lipid core nanocapsules (LNC) have been extensively studied as a new treatment strategy to improve therapeutic effects of antipsychotic drugs. We investigated the efficacy of quetiapine LNCs (QLNCs) on the poly(i:c) model of schizophrenia in both male and female rats using the pre-pulse inhibition of startle response (PPI) test paradigm after evaluating the outcomes of three different poly(i:c) doses administered to pregnant damns at GD15 on neurodevelopmental outcomes of maternal immune activation (MIA) in adult offspring. QTP solution was not capable of producing a reversal in the sensorimotor gating-disruptive effect caused by the prenatal poly(i:c) exposure. The same dose of QTP given as QLNCs significantly improved PPI-impairment. This is the first study reporting the restoration of the PPI deficits in a neurodevelopmental model of SCZ using LNCs. This is a promising delivery system strategy to improve antipsychotic effects contributing to the development of better SCZ pharmacological treatments.

Galleria mellonella Larvae as an In Vivo Model to Evaluate the Toxicity of Polymeric Nanocapsules.

Galleria mellonella larvae is an invertebrate that has been extensively used as experimental model in the investigation of microbial virulence and efficacy of antimicrobial agents and can be used to provide faster and cheaper data than traditional test systems. Our objective was to propose the use of G. mellonella larvae as an In Vivo model to evaluate the toxicity of lipid-core nanocapsule (LNC) formulations having different surface coatings. Blank LNC formulations were coated with polysorbate 80 (LNC-1), lecithin and polysorbate 80 (LNC-2), and lecithin, chitosan and polysorbate 80 (LNC-3). Subsequently, the formulations were systemically administered to G. mellonella larvae at doses of 3.75×10-14, 3.75×10-13, 3.75×10-12, 3.75×10-11 and 3.75×10-10 mols of LNC per kg of larvae. The results demonstrated that those nanocapsules having neutral (LNC-1), negative (LNC-2) or positive (LNC-3) surface did not show acute toxicity effects in G. mellonella larvae. G. mellonella larvae is a viable and promising alternative for In Vivo nanotoxicological studies. We conclude that G. mellonella larvae can be used as an alternative model for the screening of the toxicity of polymeric nanocapsules functionalized with (i) polysorbate 80, (ii) lecithin and polysorbate 80, and (iii) lecithin, chitosan and polysorbate 80. Future studies can be now developed in order to evaluate their toxicity when loaded or functionalized with drugs.

Nanoencapsulation of linseed oil with chia mucilage as structuring material: Characterization, stability and enrichment of orange juice.

Linseed oil was nanoencapsulated with chia seed mucilage (CSM) as structuring material. Linseed oil nanoparticles (LO-NP) were evaluated regarding particle size distribution, zeta potential, pH, viscosity, encapsulation efficiency, loading capacity, morphology, FT-IR and thermal properties. Furthermore, the nanoparticles were spray-dried, and oxidative stability was evaluated during 28 days under storage at accelerated conditions (40 °C). The bioaccessibility of spray dried nanoparticles (SP LO-NP) was also evaluated after in vitro digestion. Thereafter, SP LO-NP were utilized in the enrichment of orange juice, and physicochemical and sensory evaluation of pure orange juice and orange juice with SP LO-NP were evaluated. Nanoparticles in suspension presented a mean diameter of 356 ±â€¯2.83 nm, zeta potential of -22.75 ±â€¯3.89 mV and encapsulation efficiency of 52%. No significant differences regarding consumer acceptance were observed between pure orange juice and orange juice with SP LO-NP. The results suggest that CSM can be used as structuring material to nanoencapsulate hydrophobic compounds, allowing its solubility in foods with high water content. Furthermore, the SP LO-NP provided a good bioaccessibility to linseed oil after in vitro digestion, which represents an advantage to incorporate the nanoparticles in food.

Melatonin-loaded lipid-core nanocapsules protect against lipid peroxidation caused by paraquat through increased SOD expression in Caenorhabditis elegans.

BACKGROUND: Melatonin has been described in the literature as a potent antioxidant. However, melatonin presents variable, low bioavailability and a short half-life. The use of polymeric nanoparticulated systems has been proposed for controlled release. Thus, the purpose of this study was to investigate the action of melatonin-loaded lipid-core nanocapsules (Mel-LNC) in the antioxidant system of Caenorhabditis elegans, and the possible protective effect of this formulation against lipid peroxidation caused by paraquat (PQ). METHODS: The suspensions were prepared by interfacial deposition of the polymer and were physiochemically characterized. C. elegans N2 wild type and transgenic worm CF1553, muls84 [sod-3p::gfp; rol6(su1006)] were obtained from the Caenorhabditis Genetics Center (CGC). The worms were divided into 5 groups: Control, PQ 0.5 mM, PQ 0.5 mM + Mel-LNC 10 µg/mL, PQ + unloaded lipid-core nanocapsules (LNC), and PQ + free melatonin (Mel) 10 µg/mL. The lipid peroxidation was assessed through thiobarbituric acid (TBARS) levels and the fluorescence levels of the transgenic worms expressing GFP were measured. RESULTS: The LNC and Mel-LNC presented a bluish-white liquid, with pH values of 5.56 and 5.69, respectively. The zeta potential was - 6.4 ± 0.6 and - 5.2 ± 0.2, respectively. The mean particle diameter was 205 ± 4 nm and 203 ± 3 nm, respectively. The total melatonin content was 0.967 mg/ml. The TBARS levels were significantly higher in the PQ group when compared to the control group (p < 0.001). Mel-LNC reduced TBARS levels to similar levels found in the control group. Moreover, only Mel-LNC significantly enhanced the SOD-3 expression (p < 0.05). Mel-LNC was capable of protecting C. elegans from lipid peroxidation caused by PQ and this was not observed when free melatonin was used. Moreover, Mel-LNC increased the fluorescence intensity of the transgenic strain that encodes the antioxidant enzyme SOD-3, demonstrating a possible mechanism of protection from PQ-induced damage. CONCLUSION: These findings demonstrated that melatonin, when associated with nanocapsules, had improved antioxidant properties and the protective activity against PQ-induced lipid peroxidation could be associated with the activation of antioxidant enzymes by Mel-LNC in C. elegans.

Incorporation of zeaxanthin nanoparticles in yogurt: Influence on physicochemical properties, carotenoid stability and sensory analysis.

Zeaxanthin nanoparticles (Zea-NP) and zeaxanthin nanoemulsion (Zea-NE) were incorporated in yogurt. Control yogurt (CY), yogurt added of nanoparticles (Y-NP) and yogurt added of nanoemulsion (Y-NE) were evaluated weekly regarding pH, titratable acidity, color, textural parameters, viscosity and syneresis during 28 days. Zeaxanthin retention in Y-NP and Y-NE was also determined over storage. Sensory attributes and morphology were evaluated in all yogurt samples, and zeaxanthin bioaccessibility after in vitro digestion was analyzed in Y-NP and Y-NE after preparation. At the end of storage time, zeaxanthin retention was higher in Y-NP (22.31 ±â€¯2.53%) than in Y-NE (16.84 ±â€¯0.53%). Despite the lower firmness and viscosity observed in Y-NP, these changes were not sensory perceived. The bioaccessibility after in vitro digestion suggested that nanoencapsulation provided a controlled release of the carotenoid. Zea-NP can be incorporated in yogurt, allowing the dispersion of a hydrophobic compound in a hydrophilic matrix, providing stability.

Direct effects of poly(ε-caprolactone) lipid-core nanocapsules on human immune cells.

Aim: Poly(ε-caprolactone) lipid-core nanocapsules (LNCs) are efficient drug carriers and drug-free LNCs display therapeutic effects, inhibiting tumor growth and neutrophil activities. Herein, we investigated the direct actions of LNCs on human immune cells, to guide their therapeutic application. Materials & methods: LNC's uptake, cytokine release, cell migration, proliferation and intracellular pathways under inflammatory stimulation were investigated. Results & conclusion: LNCs quickly penetrated leukocytes without cytotoxicity; inhibited mitogen-induced lymphocyte proliferation, cytokine release and leukocyte migration under inflammatory stimulation, which were associated with inhibition of the MAP kinase pathway and intracellular calcium influx. Hence, we showed LNCs as a down-regulatory agent on immune cells, suggesting that either the particles themselves or their application as a drug carrier can halt non-desired inflammatory processes.

Data of characterization and related assays of lipid-core nanocapsule formulations and their hydrolysis mechanism.

The data presented here are related to the research paper entitled "Chemical stability, mass loss and hydrolysis mechanism of sterile and non-sterile lipid-core nanocapsules: the influence of the molar mass of the polymer wall," [1]. Experimental details of the nanoemulsion and nanosphere preparation. Sterilization methodology and their efficacy by microbiological analyses (turbidimetry and fungi and bacteria detection). Characterization data of formulations, LNC 1, LNC 2 and LNC 3, analyzed by laser diffraction and DLS analysis, as well as, characterization data of degradation by SEC, including all statistics analyses.

Reconstituted spray-dried phenytoin-loaded nanocapsules improve the in vivo phenytoin anticonvulsant effect and the survival time in mice.

This study evaluated the in vivo anticonvulsant effect of a spray-dried powder for reconstitution containing phenytoin-loaded lipid-core nanocapsules. The effect of chitosan coating on redispersibility, gastrointestinal stability, and drug release from nanoparticles was evaluated during the development of the powders. Maltodextrin was used as adjuvant in the spray-drying process. Chitosan coating played an important role in redispersibility, and large particles (>100 µm) were obtained using the highest concentration of solids in the feed. However, after aqueous redispersion, volume-based particle size was reduced to about 1 µm. The release of nanoparticles from the surface of the spherical microagglomerates (roundness index = 0.75) was confirmed by SEM analysis. Powders reconstituted in water recovered partially the nanometric properties of the original suspensions and were stable for 24 h. Phenytoin-loaded chitosan-coated nanocapsules and their redispersed powders have good gastrointestinal stability, and are able to control drug release in simulated gastric and intestinal fluids. Besides that, the reconstituted powder containing chitosan-coated nanocapsules exhibited improved anticonvulsant activity against seizures induced by pilocarpine in mice, compared to the non-encapsulated drug, representing an important approach in anticonvulsant treatments for children and adults.

Nanoencapsulation of chia seed oil with chia mucilage (Salvia hispanica L.) as wall material: Characterization and stability evaluation.

In this study, chia seed oil was nanoencapsulated utilizing chia seed mucilage (CSM) as wall material. The viscosity, encapsulation efficiency, loading capacity, transmission electron microscopy, FT-IR spectroscopy and thermal properties of chia seed oil nanoparticles (CSO-NP) were performed after preparation. Particle size, zeta potential, span value, and pH of CSO-NP and oxidation stability of nanoencapsulated and unencapsulated oil were evaluated during 28days of storage at accelerated conditions (40°C). The CSO-NP showed spherical shape, an average size of 205±4.24nm and zeta potential of -11.58±1.87mV. The encapsulation efficiency (82.8%), loading capacity (35.38%) and FT-IR spectroscopy demonstrated the interaction between oil and mucilage. Furthermore, CSO-NP were thermally stable at temperatures up 300°C and nanoencapsulated oil showed higher stability against oxidation than unencapsulated oil. The results suggest that chia seed mucilage represents a promising alternative to substitute synthetic polymers in nanoencapsulation.

Pre-clinical investigation of the modulation of quetiapine plasma pharmacokinetics and tissues biodistribution by lipid-core nanocapsules.

This study aims to investigate the changes in plasma pharmacokinetics and liver and brain distribution of quetiapine (QTP) due to its encapsulation into a polymeric nanocarrier. For this reason a bioanalytical method was developed and validated in order to quantify QTP in plasma, liver and brain tissue samples. The method was linear over the concentration range of 0.025-3.0µg.mL (r(2)>0.98), accurate, precise (R.S.D<±15%) and the recoveries, stability and validation parameters are within the acceptable limits determined by international guidelines. Plasma pharmacokinetics, cerebral and hepatic distribution of the drug were carried out after intravenous administration of 5mgkg(-1) of nanoencapsulated (QLNC) or free-QTP to male Wistar rats. Increasing half-life was observed for QLNC in relation to free-QTP due to o significant decrease in total clearance. QTP volume of distribution was not altered due to encapsulation. An increase in QTP liver exposure was observed after nanoencapsulation probably due to a reduction in drug metabolization process.