Efficacy and safety of a 0.05 % nanoencapsulated imiquimod hydrogel for the treatment of actinic cheilitis: Drug release analysis and clinical study.

Actinic cheilitis (AC) is a lip disorder, with no standard treatment. Imiquimod (IMIQ) is an immunomodulator that treat precancerous lesions; however, its commercial form causes severe adverse effects. This study aimed to assess IMQ release from a chitosan hydrogel containing 0.05 % nanoencapsulated (NANO) imiquimod (IMIQ-0.05 %-NANO) and its efficacy in AC treatment. The hydrogels were prepared by incorporating chitosan into polymeric nanocapsules (NCimiq) loaded with IMQ, produced using the interfacial deposition of preformed polymer method. IMQ release was evaluated using automated Franz Cells. A triple-blind randomized controlled trial (49 subjects) compared the efficacy of: IMIQ-0.05 %-NANO, 5 % free imiquimod (IMIQ-5 %), 0.05 % free imiquimod (IMIQ-0.05 %), and placebo hydrogel. The IMIQ-NANO-0.05 % and IMIQ-5 % groups exhibited significantly higher rates of clinical improvement (p < 0.05); however, the IMIQ-5 % group experienced more adverse effects (92.3 % of subjects) compared to other groups (p < 0.05). In conclusion, in the studied sample, IMIQ-NANO-0.05 % was a safe and effective option to treat AC.

Diazepam nanocapsules as an alternative for sleep induction: Development study and toxicity assessment.

Diazepam (DZP) is a sedative medication prescribed to treat anxiety and as a sleep inducer, although its residual effects are unfavorable to patients. Nanotechnology represents a tool to improve the pharmacological characteristics of drugs, reducing their side effects. This study aimed to develop and characterize DZP nanocapsules and to evaluate their toxicity in alternative models and the hypnotic-sedative effect in mice. Nanocapsules were prepared by the nanoprecipitation method and properly characterized. Long-term and accelerated stability studies were performed. The in vitro release profile was determined by diffusion in Franz cells. The safety of the formulation was evaluated in the Caenorhabditis elegans (C. elegans) and the oral acute toxicity in mice. Pharmacological evaluation was performed using thiopental-induced sleeping time. DZP was successfully incorporated into Poly-(ɛ-caprolactone) (PCL) nanocapsules, with high entrapment efficiency. The nanocapsule did not affect the development or survival of C. elegans, different from the free drug, which affected the nematode development at the higher tested dose. No signs of toxicity, nor body mass or feed consumption changes were observed during the 14 days evaluated. Finally, this innovative formulation carrying DZP can produce a hypnotic-effect at a reduced dose compared to the free drug, with no toxicity in alternative models.

Indole-3-carbinol loaded-nanocapsules modulated inflammatory and oxidative damages and increase skin wound healing in rats.

This study evaluated the effects of topically applied hydrogels (HG) containing nanoencapsulated indol-3-carbinol (I3C) and its free form in a rat model of skin wounds. Formulations were topically applied twice a day for five days to the wounds. On days 1, 3, and 6, the wound area was measured to verify the % of regression. On the sixth day, the animals were euthanized for the analysis of the inflammatory and oxidative profile in wounds. The nanocapsules (NC) exhibited physicochemical characteristics compatible with this kind of suspension. After five hours of exposure to ultraviolet C, more than 78% of I3C content in the suspensions was still observed. The NC-I3C did not modify the physicochemical characteristics of HG when compared to the HG base. In the in vivo study, an increase in the size of the wound was observed on the 3rd experimental day, which was lower in the treated groups (mainly in HG-NC-I3C) compared to the control. On the 6th day, HG-I3C, HG-NC-B, and HG-NC-I3C showed lower regression of the wound compared to the control. Additionally, HG-NC-I3C exhibited an anti-inflammatory effect (as observed by decreased levels of interleukin-1B and myeloperoxidase), reduced oxidative damage (by decreased reactive species, lipid peroxidation, and protein carbonylation levels), and increased antioxidant defense (by improved catalase activity and vitamin C levels) compared to the control. The current study showed more satisfactory results in the HG-NC-I3C group than in the free form of I3C in decreasing acute inflammation and oxidative damage in wounds.

I3C nanocapsules exhibited characteristics compatible with this kind of suspension;On 3rd day, I3C nanocapsules prevented the increase of wound area;I3C nanocapsules decreased oxidative damage in wound tissue;Inflammatory proteins were decreased in I3C nanocapsules treated group.

Development and pharmacological evaluation of liposomes and nanocapsules containing paroxetine hydrochloride.

Depression is one of the most common psychiatric disorders. Nanotechnology has emerged to optimize the pharmacological response. Therefore, the aim of this work was to develop and characterize liposomes and nanocapsules containing paroxetine hydrochloride and evaluate their antidepressant-like effect using the open field and tail suspension tests in mice. Liposomes and nanocapsules were prepared using the reverse-phase evaporation and nanoprecipitation methods, respectively. The particle size of the formulation ranged from 121.81 to 310.73 nm, the polydispersity index from 0.096 to 0.303, the zeta potential from -11.94 to -34.50 mV, the pH from 5.31 to 7.38, the drug content from 80.82 to 94.36 %, and the association efficiency was 98 %. Paroxetine hydrochloride showed slower release when associated with liposomes (43.82 %) compared to nanocapsules (95.59 %) after 10 h. In Vero cells, in vitro toxicity showed a concentration-dependent effect for paroxetine hydrochloride nanostructures. Both nanostructures decreased the immobility time in the TST at 2.5 mg/kg without affecting the number of crossings in the open field test, suggesting the antidepressant-like effect of paroxetine. In addition, the nanocapsules decreased the number of groomings, reinforcing the anxiolytic effect of this drug. These results suggest that the nanostructures were effective in preserving the antidepressant-like effect of paroxetine hydrochloride even at low doses.

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.

Polymeric Nanocapsules Containing Ozonated Oil and Terbinafine Hydrochloride as a Potential Treatment Against Dermatophytes.

Terbinafine hydrochloride is a synthetic allylamine whose mechanism of action consists of inhibiting the enzyme squalene epoxidase that participates in the first stage of ergosterol synthesis, interfering with fungal membrane function. Ozonated oils are used for topical application of ozone, producing reactive oxygen species that cause cellular damage in microorganisms, therefore being an alternative treatment for acute and chronic skin infections. This study aimed to develop and characterize Eudragit® RS100 nanocapsules, obtained by interfacial deposition of preformed polymer method, containing 0.5% terbinafine hydrochloride and 5% ozonated sunflower seed oil as a potential treatment against dermatophytes. The polymeric nanocapsules were characterized regarding particle size, zeta potential, pH, drug content, encapsulation efficiency, and stability. The in vitro drug release, in vitro skin permeation, and in vitro antifungal activity were also evaluated. The particle size was around 150 nm with a narrow size distribution, the zeta potential was around + 6 mV, and the pH was 2.2. The drug content was close to 95% with an encapsulation efficiency of 53%. The nanocapsules were capable to control the drug release and the skin permeation. The in vitro susceptibility test showed greater antifungal activity for the developed nanocapsules, against all dermatophyte strains tested, compared to the drug solution. Therefore, the polymeric nanocapsules suspension containing terbinafine hydrochloride and ozonated oil can be considered a potential high-efficacy candidate for the treatment of dermatophytosis, with a possible reduction in the drug dose and frequency of applications. Studies to evaluate safety and efficacy in vivo still need to be performed.

Formulation of benznidazole-lipid nanocapsules: Drug release, permeability, biocompatibility, and stability studies.

Benznidazole, a poorly soluble in water drug, is the first-line medication for the treatment of Chagas disease, but long treatment periods at high dosages cause several adverse effects with insufficient activity in the chronic phase. According to these facts, there is a serious need for novel benznidazole formulations for improving the chemotherapy of Chagas disease. Thus, this work aimed to incorporate benznidazole into lipid nanocapsules for improving its solubility, dissolution rate in different media, and permeability. Lipid nanocapsules were prepared by the phase inversion technique and were fully characterized. Three formulations were obtained with a diameter of 30, 50, and 100 nm and monomodal size distribution with a low polydispersity index and almost neutral zeta potential. Drug encapsulation efficiency was between 83 and 92 % and the drug loading was between 0.66 and 1.04 %. Loaded formulations were stable under storage for one year at 4 °C. Lipid nanocapsules were found to protect benznidazole in simulated gastric fluid and provide a sustained release platform for the drug in a simulated intestinal fluid containing pancreatic enzymes. The small size and the almost neutral surface charge of these lipid nanocarriers improved their penetration through mucus and such formulations showed a reduced chemical interaction with gastric mucin glycoproteins. LNCs. The incorporation of benznidazole in lipid nanocapsules improved the drug permeability across intestinal epithelium by 10-fold compared with the non-encapsulated drug while the exposure of the cell monolayers to these nanoformulations did not affect the integrity of the epithelium.

Cationic nanocapsule suspension as an alternative to the sublingual delivery of nifedipine.

Nifedipine (NIFE) is a calcium channel blocker drug used to treat cardiovascular diseases, angina, and hypertension. However, NIFE is photolabile, has a short biological half-life, low aqueous solubility, and undergoes an intense first-pass effect, compromising its oral bioavailability. Thus, this study aimed to develop NIFE-loaded nanocapsules for sublingual administration. Nanocapsule suspensions of Eudragit® RS100 and medium chain triglycerides containing NIFE were prepared by the interfacial deposition of preformed polymer technique. The developed formulations showed particle size around 170 nm, polydispersity index below 0.2, positive zeta potential, and acid pH. The NIFE content was 0.98 ± 0.03 mg/mL, and the encapsulation efficiency was 99.9%. The natural light photodegradation experiment showed that the nanocapsules were able to provide NIFE photoprotection. The nanocapsules reduced the cytotoxicity of NIFE and showed no genotoxic effects in the Allium cepa model. Through the HET-CAM test, the formulations were classified as non-irritating. The developed nanocapsule suspension demonstrated a controlled release of NIFE and mucoadhesive potential. The in vitro permeation assay showed that the nanocapsules favored the NIFE permeation to the receptor compartment. In addition, the nanocapsules provided greater drug retention in the mucosa. Thus, the development of polymeric nanocapsule suspensions showed that this system could be a promising platform for NIFE sublingual administration.

Ameliorating the antiparasitic activity of the multifaceted drug ivermectin through a polymer nanocapsule formulation.

Ivermectin (IVM) is a potent antiparasitic widely used in human and veterinary medicine. However, the low oral bioavailability of IVM restricts its therapeutic potential in many parasitic infections, highlighting the need for novel formulation approaches. In this study, poly(ε-caprolactone) (PCL) nanocapsules containing IVM were successfully developed using the nanoprecipitation method. Pumpkin seed oil (PSO) was used as an oily core in the developed nanocapsules. Previously, PSO was chemically analyzed by headspace solid-phase microextraction coupled to gas chromatography/mass spectrometry (HS-SPME/GC-MS). The solubility of IVM in PSO was found to be 4266.5 ± 38.6 µg/mL. In addition, the partition coefficient of IVM in PSO/water presented a logP of 2.44. A number of nanocapsule batches were produced by factorial design resulting in an optimized formulation. Negatively charged nanocapsules measuring around 400 nm demonstrated unimodal size distribution, and presented regular spherical morphology under transmission electron microscopy. High encapsulation efficiency (98-100%) was determined by HPLC. IVM-loaded capsules were found to be stable in nanosuspensions at 4 °C and 25 °C, with no significant variations in particle size observed over a period of 150 days. Nanoencapsulated IVM (0.3 mM) presented reduced toxicity to J774 macrophages and L929 fibroblasts compared to free IVM. Moreover, IVM-loaded nanocapsules also demonstrated enhanced in vitro anthelmintic activity against Strongyloides venezuelensis in comparison to free IVM. Collectively, the present findings demonstrate the promising potential of PCL-PSO nanocapsules to improve the antiparasitic effects exerted by IVM.

PEGylated and functionalized polylactide-based nanocapsules: An overview.

Polymeric nanocapsules (NC) are versatile mixed vesicular nanocarriers, generally containing a lipid core with a polymeric wall. They have been first developed over four decades ago with outstanding applicability in the cosmetic and pharmaceutical fields. Biodegradable polyesters are frequently used in nanocapsule preparation and among them, polylactic acid (PLA) derivatives and copolymers, such as PLGA and amphiphilic block copolymers, are widely used and considered safe for different administration routes. PLA functionalization strategies have been developed to obtain more versatile polymers and to allow the conjugation with bioactive ligands for cell-targeted NC. This review intends to provide steps in the evolution of NC since its first report and the recent literature on PLA-based NC applications. PLA-based polymer synthesis and surface modifications are included, as well as the use of NC as a novel tool for combined treatment, diagnostics, and imaging in one delivery system. Furthermore, the use of NC to carry therapeutic and/or imaging agents for different diseases, mainly cancer, inflammation, and infections is presented and reviewed. Constraints that impair translation to the clinic are discussed to provide safe and reproducible PLA-based nanocapsules on the market. We reviewed the entire period in the literature where the term "nanocapsules" appears for the first time until the present day, selecting original scientific publications and the most relevant patent literature related to PLA-based NC. We presented to readers a historical overview of these Sui generis nanostructures.

Safety assessment of different unloaded polymeric nanocapsules in Caenorhabditis elegans.

Nano-sized drug delivery systems have been the subject of intense research in recent years because polymeric materials allow the absorption and release of active substances in a controlled manner. Despite the benefits, the safety of nanoparticulate systems is an aspect to be understood, particularly in vivo systems. Caenorhabditis elegans is a very useful alternative model for nanotoxicology and has been recently applied in this field. The aim of this study was to evaluate toxicological endpoints in C. elegans exposed to nanocapsules (NC) prepared with different coatings: polysorbate 80 (NCP80); polyethylene glycol (NCPEG), Eudragit® RS 100 (NCEUD) and chitosan (NCCS). Nanocapsules were prepared by nanoprecipitation method and showed acceptable physico-chemical characterization. Polyethylene glycol nanocapsules and chitosan nanocapsules increased worms lethality in a dose-dependent manner in acute exposure; polysorbate 80 nanocapsules, polyethylene glycol nanocpsules and chitonan nanocapsules also increased lethality following chronic exposure. Chitosan nanocapsules were the most toxic in all exposures, demonstrating toxicity even at low concentrations. Reproduction and body length were not affected by any of the nanocapsules exposures. The expression of superoxide dismutase showed that polysorbate 80 nanocapsules at the highest concentration slightly increased SOD-3::GFP expression. On the other hand, chitosan nanocapsules exposure blunted SOD-3 expression. This work demonstrates the toxicological differences between nanocapsule produced with different coatings and indicates higher safety for the use of eugragit nanocapsule in new formulations for future drug delivery and targeting systems.

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.

Production of methylcellulose films functionalized with poly-ε-caprolactone nanocapsules entrapped ß-carotene for food packaging application.

Nowadays, there is a worldwide demand in the production of innovative packaging that release active compounds to increase the shelf life of perishable food products. Therefore, this study produced methylcellulose films functionalized with poly-ε-caprolactone nanocapsules entrapped ß-carotene. The nanoparticles were produced by the nanoprecipitation method, and 10, 30, and 50 % of nanoparticles colloidal solution was added in the methylcellulose filmogenic solution. The films were characterized by the mechanical, physicochemical properties, antioxidant activity, and release of ß-carotene from the polymeric matrix to a food simulant. The results demonstrated satisfactory mechanical properties; however, the addition of nanoparticles decreased the Young's Modulus and increased the elongation at break. Regarding light transmission, the incorporation of ß-carotene nanoparticles promoted a decrease in the percentage of ultraviolet ray's transmittance through the film matrix, as well as visible light. The incorporation of nanoparticles improved the antioxidant activity of the films, which was proportional to the concentration of ß-carotene used in the formulation. The release of ß-carotene reached a maximum value of 10.93 µg g-1 film containing 70 % nanoparticles, which was a desired profile for food application. Finally, the methylcellulose films functionalized with poly-ε-caprolactone nanocapsules can release ß-carotene, and therefore, can be considered as a novel nanomaterial for food conservation, with a potential to increase the shelf life of perishable food products.

In vivo and in vitro per se effect evaluation of Polycaprolactone and Eudragit® RS100-based nanoparticles.

Biodegradable polymeric nanocapsules (NC) present incredible characteristics as drug nanocarriers that optimize drug targeting. However, However, a more detailed isolated effect of polymer-based nanoparticles as drug carriers is required. This work aimed to evaluate the per se effect of blank-NC (NC-B) with different surface characteristics both in vitro and in vivo toxicity. NC1-B (Polysorbate 80 coated poly(ɛ-caprolactone) NC), NC2-B (polyethylene glycol 6000 coated poly(ɛ-caprolactone) NC), NC3-B (chitosan-coated poly(ɛ-caprolactone) NC) and NC4-B (Eudragit® RS100 NC) were prepared by nanoprecipitation method. Formulations were characterized by particle size, zeta potential, and pH. The in vitro cytotoxicity tests against tumor cell lines were performed (HepG2 and MCF-7). Antiviral activity was evaluated by MTT in Vero cells infected with HSV-1 (KOS strain). In vivo evaluation was performed in apomorphine-induced stereotypy in Wistar rats and locomotor activity distance, head movements, and rearing behavior were measured. NC1-B, NC2-B, NC3-B, and NC4-B had a diameter under 350 nm. The pH and zeta potential of formulations varied according to their coating. For in vitro evaluation of antitumor activity and antiviral activity, one-way ANOVA showed no significant differences in cell viability. In vivo tests showed low neurological effects. In conclusion, different surface characteristics of NC-B did not demonstrate toxicity against the evaluated cell lines HepG2 and MCF-7, antiviral effect against HSV-1, and the neurological effects in a stereotyping model were low and may be attributed to the per se effect of NC-B.

Artemether-loaded polymeric lipid-core nanocapsules reduce cell viability and alter the antioxidant status of U-87 MG cells.

Glioblastomas are tumors that present a high mortality rate. Artemether (ART) is a lactone with antitumor properties, demonstrating low bioavailability and water solubility. In the present study, we developed lipid-core nanocapsules (LNC) containing pequi oil (Caryocar brasiliense Cambess) as the oily core for ART-loaded LNCs (LNCART) and evaluated their effect on human glioblastoma cells (U-87 MG). LNCs were developed by interfacial deposition of a preformed polymer, followed by physicochemical characterization. LNCART revealed a diameter of 0.216 µm, polydispersity index of 0.161, zeta potential of -12.0 mV, and a pH of 5.53. Furthermore, mitochondrial viability, proliferation, total antioxidant status, and antioxidant enzyme activity were evaluated. ART reduced cell viability after 24 h and proliferation after 48 h of treatment at concentrations equal to or above 40 µg . mL-1. LNCART, at 1.25 µg . mL-1, reduced these parameters after 24 h of treatment. Furthermore, superoxide dismutase (SOD) activity was elevated, while glutathione reductase (GR) activity was reduced. These findings suggest that ART loaded into LNC may be a promising alternative to improve its pharmacological action and possible application as a therapeutic agent for glioblastoma.

Polymeric Nanorepellent Systems Containing Geraniol and Icaridin Aimed at Repelling Aedes aegypti.

Repellents are among the leading products used against diseases transmitted by the Aedes aegypti mosquito. However, their indiscriminate use or high concentrations can cause severe adverse reactions, particularly in children and pregnant women. To protect them, nanotechnology is a promising tool to encapsulate active compounds against degradation, increase their effectiveness, and decrease their toxicity, as it can promote the modified release of the active compound. This study aimed to develop polymeric nanocapsules containing the repellent actives geraniol and icaridin using low concentrations of the active component, with the objective of promoting effective activity and greater safety against adverse reactions. The nanocapsules were developed by the interfacial deposition method, and the physicochemical properties of the nanocapsules were evaluated using dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), zeta potential, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), release kinetics assay, and mathematical modeling. Cell viability was assessed by the MTT assay and genotoxicity analysis using the comet assay. The developed nanocapsules containing geraniol and icaridin showed mean diameters of 260 nm and 314 nm, respectively, with a polydispersity index < 0.2. The nanocapsules showed encapsulation efficiency values of 73.7 ± 0.1% for icaridin and 98.7 ± 0.1% for geraniol. Morphological analysis showed spherical nanocapsules with low polydispersity. The kinetic parameters calculated using the Korsmeyer−Peppas model indicated an anomalous release profile. Cell viability and genotoxicity analyses showed that the nanocapsules did not alter cell viability or damage DNA. The results demonstrate a promising nanostructured system with good physicochemical characteristics and good stability, with repellent activity against Aedes aegypti.

Evaluation of an Efficient and Skin-Adherent Semisolid Sunscreen Nanoformulation.

INTRODUCTION: Sunscreens are substances applied on the skin surface to protect the skin from the harmful effects of UV light. Nanoparticles can increase the retention time of the sunscreen on the skin surface and its efficacy, by acting as physical barriers. The present investigation aimed to evaluate the influence of the chitosan coating of benzophenone-3-loaded lipid-core nanocapsules (CH-LCN) on the skin adhesion and photoprotective effect of the sunscreen. METHODS: CH-LNC were obtained by the interfacial deposition of preformed polymer. A suitable semisolid formulation was obtained by using hydroxyethyl cellulose as the gel-forming polymer. Skin adhesion experiments were performed in vitro by applying the formulation on porcine skin and keeping it under water at 32 °C for up to 60 min. Photoprotective effect was analyzed in vitro by the capacity of the formulations to protect a photo unstable substance (resveratrol) from degradation under UV light. RESULTS: CH-LNC presented size of around 150 nm, with low polydispersity, positive zeta potential, due to chitosan, and benzophenone-3 encapsulation efficiency of close to 100% (3 mg/mL). The proposed gel presented suitable consistence and pH for skin application and benzophenone-3 concentration of around 3 mg/g. Although coated and uncoated lipid-core nanocapsules increased benzophenone-3 skin adhesion after 10 min of water immersion, only the nanoparticles coated with chitosan were able to do so after 60 min. The chitosan coating of the nanocapsules increased the photoprotection of the sunscreen under UVA and UVB light after 60 min of exposure, probably due to the film-forming properties of chitosan. CONCLUSION: The chitosan coating of CH-LCN increased the skin adhesion and the photoprotective effect of the sunscreen.

Combination of selol nanocapsules and magnetic hyperthermia hinders breast tumor growth in aged mice after a short-time treatment.

Short time treatment with reduced dosages of selol-loaded PLGA nanocapsules (NcSel) combined with magnetic hyperthermia (MHT) is evaluated in aged Erhlich tumor-bearing mice. Clinical, hematological, biochemical, genotoxic and histopathological parameters are assessed during 7 d treatment with NcSel and MHT, separately or combined. The time evolution of the tumor volume is successfully modeled using the logistic mathematical model. The combined therapy comprising NcSel and MHT is able to hinder primary tumor growth and a case of complete tumor remission is recorded. Moreover, no metastasis was diagnosed and the adverse effects are negligible. NcSel plus MHT may represent an effective and safe alternative to cancer control in aged patients. Future clinical trials are encouraged.

Photodynamic therapy with the dual-mode association of IR780 to PEG-PLA nanocapsules and the effects on human breast cancer cells.

IR780 is a near-infrared fluorescent dye, which can be applied as a photosensitizer in photodynamic (PDT) and photothermal (PTT) therapies and as a biodistribution tracer in imaging techniques. We investigated the growth and migration inhibition and mechanism of death of breast tumor cells, MCF-7 and MDA-MB-231, exposed to polymeric nanocapsules (NC) comprising IR780 covalently linked to the biodegradable polymer PLA (IR-PLA) and IR780 physically encapsulated (IR780-NC) in vitro. Both types of NC had mean diameters around 120 nm and zeta potentials around -40 mV. IR-PLA-NC was less cytotoxic than IR780 NC to a non-tumorigenic mammary epithelial cell line, MCF-10A, which is an important aspect of selectivity. Free-IR780 was more cytotoxic than IR-PLA-NC for MCF-7 and MDA-MB-231 cells after illumination with a 808 nm laser. IR-PLA NC was effective to inhibit colony formation (50%) and migration (30-40%) for both cancer cell lines. MDA-MB-231 cells were less sensitive to all IR780 formulations compared to MCF-7 cells. Cell uptake was higher with IR-PLA-NC than with IR780-NC and free-IR780 in both cancer cell lines (p < 0.05). NC uptake was higher in MCF-7 than in MDA-MB-231 cells. IR-PLA-NC induced a higher percentage of apoptosis upon illumination in MDA-MB-231 than in MCF-7 cells. The necrosis mechanism of death predominated in treatments with free-IR780 and with encapsulated IR780 NC, suggestive of damages at the plasma membrane. IR780 conjugated with PLA increased the apoptotic pathway and demonstrated potential as a multifunctional theranostic agent for breast cancer treatment with increased cellular uptake, photodynamic activity and more reliable tracking in cell-image studies.

Ferulic acid-loaded nanocapsules: Evaluation of mucosal interaction, safety and antioxidant activity in human mononucleated cells.

Ferulic acid (FA) is a phenolic compound that has antioxidant, anti-inflammatory and anticarcinogenic properties besides presenting cytoprotective activity. It has limited oral bioavailability what is a challenge to its therapeutic application. In this way, this investigation aimed to develop FA-loaded nanocapsule suspensions (NC-FA) prepared with ethylcellulose and evaluate their in vitro release profile, mucoadhesion and irritation potential; scavenging capacity, cytotoxicity, cytoprotection and genoprotection against hydrogen peroxide-induced damage in hMNC (human Mononucleated Cells) culture. The nanocapsules presented physicochemical characteristics compatible with colloidal systems (NC-FA: 112 ± 3 nm; NC-B (without FA): 107 ± 3 nm; PdI < 0.2; Span<2.0 and negative zeta potential). In addition, the nanoparticulate system promoted the FA controlled release, increasing the half-life twice through the in vitro dialysis method. NC-FA and NC-B were able to interact with mucin, which is an indicative of mucoadhesive properties and the association of FA with nanocapsules showed decreased irritation by HET-CAM method. Besides, the NC-FA did not present cytotoxicity in hMNC and improved the ATBS radical scavenging capacity. Besides, it prevented, treated and reversed oxidative conditions in a H2O2-induced model in hMNC. Thus, this nanocarrier formulation is promising to perform more preclinical investigations focusing on diseases involving oxidative mechanisms.