Nanocapsule Formulations Research Articles

Effects of UV-C and Edible Nano-Coating as a Combined Strategy to Preserve Fresh-Cut Cucumber.

The objective of this study was to evaluate the effectiveness of a combination of UV-C disinfection treatment and a nano-coating lemon essential oil nanocapsules. The nanocapsules were prepared by ionic gelation with an alginate-pectin wall and the lemon essential oil had a particle size of 219 ± 22 nm and a zeta potential of −7.91 ± 0.18 mV. The lemon essential oil had an encapsulation efficiency of 68.19 ± 1.18%. The fresh-cut cucumber was stored for 15 days at 4 °C. Six formulations of nanocapsules were evaluated, and hydroxypropyl methylcellulose was used as matrix polysaccharide in four coatings. Three formulations were treated with UV-C at 4.5 kJ/m2. The results showed that the combination of UV-C and nano-coatings (lemon essential oil = 200 mg/L) increased the shelf life by up to 15 days. Using UV-C and nano-coatings, the ∆E value was 7.12 at the end of the storage period, while the Control samples had an ∆E of 28.1. With nano-coating treatment, the amount of polyphenols decreased by 23% within 9 days. In contrast, with combined UV-C and nano-coating treatment, the amount of polyphenols was reduced by 38.84% within 15 days. The antioxidant capacity remained stable at 459 μmol TE/100 g for the fresh product when the combined treatment was used. A good correlation was also observed between the increasing of the fruit’s shelf life and decreasing of its enzymatic activity. The inclusion of UV-C treatment contributed to the reduction in the initial total bacteria at 3.30 log CFU/g and its combination with nano-coatings helped in the control of microbial growth during storage.

Hyaluronic Acid-Based Nanocapsules as Efficient Delivery Systems of Garlic Oil Active Components with Anticancer Activity.

Diallyl disulfide (DADS) and diallyl trisulfide (DATS) are garlic oil compounds exhibiting beneficial healthy properties including anticancer action. However, these compounds are sparingly water-soluble with a limited stability that may imply damage to blood vessels or cells after administration. Thus, their encapsulation in the oil-core nanocapsules based on a derivative of hyaluronic acid was investigated here as a way of protecting against oxidation and undesired interactions with blood and digestive track components. The nuclear magnetic resonance (1H NMR) technique was used to follow the oxidation processes. It was proved that the shell of the capsule acts as a barrier limiting the sulfur oxidation, enhancing the stability of C=C bonds in DADS and DATS. Moreover, it was shown that the encapsulation inhibited the lysis of the red blood cell membrane (mainly for DADS) and interactions with serum or digestive track components. Importantly, the biological functions and anticancer activity of DADS and DATS were preserved after encapsulation. Additionally, the nanocapsule formulations affected the migration of neoplastic cells—a desirable preliminary observation concerning the inhibition of migration. The proposed route of administration of these garlic extract components would enable reaching their higher concentrations in blood, longer circulation in a bloodstream, and thus, imply a better therapeutic effect.

α-amyrin-loaded nanocapsules produce selective cytotoxic activity in leukemic cells

IntroductionAmyrins are triterpenes that have attractive pharmacological potential; however, their low water solubility and erratic stomach absorption hinders their use as a drug. The aim of this paper was to develop a novel α-amyrin-loaded nanocapsule for intestinal delivery and evaluate, preliminarily, its cytotoxic ability against leukemic cells. Material and methodsFive nanocapsule formulations were designed by the solvent displacement-evaporation method. Poly-ε-caprolactone, Eudragit® E100, and Kollicoat® Mae 100 P were used as film-former materials. Particle size, polydispersity index (PdI), zeta potential, and the pH of all formulations were measured. The cytotoxic potential of the nanocapsules was evaluated in vitro using different leukemic lineages ResultsNanocapsules coated with Kollicoat® Mae 100 P presented the smallest particle size (130 nm), the lowest zeta-potential (−38 mV), and the narrowest size distribution (PdI = 0.100). The entrapment efficiency was 65.47%, while the loading capacity was 2.40%. Nanocapsules release 100% of α-amyrin in 40 min (pH 7.4), by using a possible mechanism of swelling-diffusion. The formulation showed excellent on-shelf physicochemical stability during one year. Additionally, nanocapsules produced a selective cytotoxic effect on a human leukemia lineage Kasumi-1, an acute myeloid leukemia cell line, and produced cell death by apoptosis Conclusionα-amyrin-loaded nanocapsules appear to be a promising nanoformulation that could be used against leukemia.

Lipid-based nanocarriers co-loaded with artemether and triglycerides of docosahexaenoic acid: Effects on human breast cancer cells

Artemether (ART) was combined with triglyceride of docosahexaenoic acid (DHA) as the lipid-core in nanoemulsions (NE), nanostructured lipid carriers (NLC), and PEG-PLA nanocapsules (NC) formulations, and their effects on human breast cancer cells were evaluated. ART has been extensively used for malaria and has also therapeutic potential against different tumor cells in a repositioning strategy. The concentration-dependent cytotoxicity in vitro was determined in tumor lineages, MDA-MB-231 and MCF-7, and non-tumor MCF-10A cells for free-ART/DHA combination and its formulations. The cells were monitored for viability, effects on cell migration and clonogenicity, cell death mechanism, and qualitative and quantitative cell uptake of nanocarriers. The lipid-nanocarriers showed mean sizes over the range of 110 and 280 nm with monodisperse populations and zeta potential values ranging from −21 to −67 mV. The ART encapsulation efficiencies varied from 57 to 83 %. ART/DHA co-loaded in three different lipid nanocarriers reduced the MDA-MB-231 and MCF-7 viability in a dose-dependent manner with enhanced selectivity toward tumor cell lines. They also reduced clonogenicity and the ability of cells to migrate showing antimetastatic potential in both cell lines and triggered apoptosis in MCF-7 cells. Confocal microscopy and flow cytometry analysis showed that NC, NLC, and NE were rapidly internalized by cells, with higher interaction displayed by NE with MCF-7 cells compared to NC and NLC that was correlated with the strongest NE-fluorescence in cells. Therefore, this study not only demonstrated the value of this new combination of ART/DHA as a new strategy for breast cancer therapy but also showed enhanced cytotoxicity and potential metastatic activity of lipid-based formulations against human breast cancer cells that indicate great potential for pre-clinical and clinical translation.

Erlotinib entrapped in cholesterol-depleting cyclodextrin nanoparticles shows improved antitumoral efficacy in 3D spheroid tumors of the lung and the liver

Erlotinib (ERL), a tyrosine kinase inhibitor approved for therapeutic use in non-small cell lung cancer is further researched for eventual liver cancer treatment. However, conventional ERL has important bioavailability problems resulting from oral administration, poor solubility and gastrointestinal degradation into inactive metabolites. Alternative administration routes and nanoparticulate drug delivery systems are studied to prevent or reduce these drawbacks. In this study, ERL-loaded CD nanosphere and nanocapsule formulations capable of cholesterol depletion in resistant cancer cells were evaluated for ERL delivery. Drug loading and release profile depended largely on the surface charge of nanoparticles. Antiproliferative activity data obtained from 2D and 3D cell culture models demonstrated that polycationic βCD nanocapsules were the most effective formulation for ERL delivery to lung and liver cancer cells. 3D tumour tumoral penetration studies further revealed that nanocapsule formulations penetrated deeper into the tumour through the multilayered cells. Furthermore, all formulations were able to extract membrane cholesterol from lung and liver cancer cell lines, indicating the induction of apoptosis and overcoming drug resistance. In conclusion, given their tumoral penetration and cell membrane cholesterol depletion abilities, amphiphilic CD nanocapsules emerge as promising alternatives to improve the safety and efficiency of ERL treatment of both liver and lung tumours.

PEGylated polymeric nanocapsules for oral delivery of trypsin targeted to the small intestines

The lack of trypsin in the intestines may end up with malnutrition; thus, trypsin replacement therapy is required in such cases. The main objective of this study is to formulate and evaluate polymeric nanocapsule (PNC) systems able to deliver trypsin to the small intestines with the minimal release in the stomach with the maximum biological activity. Four nanocapsule formulations were prepared by double emulsion/evaporation method as w/o/w and s/o/w. Particle size, encapsulation efficiencies, drug release in simulated gastric fluids (SGF) and simulated intestinal fluids (SIF), morphology, the biological activity of encapsulated trypsin and shelf-life stability were investigated for all formulations. All formulations had a spherical shape with submicron size, and encapsulation efficiency more than 80%. The biological activity of encapsulated trypsin was significantly affected by the amount of trehalose and whether the formulations were prepared as s/o/w or w/o/w (P < 0.05). Most of the encapsulated protein was released sustainedly at the target site (SIF) over 24 h with minimum amount release in the gastric fluids. Also, more than 90% of physical integrity trypsin encapsulated in all formulations was retained after storage under chilled conditions for six months. However, the enzymatic assay results show that with low trehalose content, the biological activity was low, while increasing the trehalose amount increased the shelf stability to reach around 100% after six months of the study. The results obtained in this research work clearly indicated a promising potential of controlled release polymeric nanocapsules containing trypsin to target the small intestine and protect trypsin from the harsh condition facing the proteins during the process of preparation or the period of storage.

Multidisciplinary Preclinical Investigations on Three Oxamniquine Analogues as New Drug Candidates for Schistosomiasis*.

Schistosomiasis is a disease of poverty affecting millions of people. Praziquantel (PZQ), with its strengths and weaknesses, is the only treatment available. We previously reported findings on three lead compounds derived from oxamniquine (OXA), an old antischistosomal drug: ferrocene-containing (Fc-CH2 -OXA), ruthenocene-containing (Rc-CH2 -OXA) and benzene-containing (Ph-CH2 -OXA) OXA derivatives. These derivatives showed excellent in vitro activity against both Schistosoma mansoni larvae and adult worms and S. haematobium adult worms, and were also active in vivo against adult S. mansoni. Encouraged by these promising results, we conducted additional in-depth preclinical studies and report in this investigation on metabolic stability studies, in vivo studies on S. haematobium and juvenile S. mansoni, computational simulations, and formulation development. Molecular dynamics simulations supported the in vitro results on the target protein. Though all three compounds were poorly stable within an acidic environment, they were only slightly cleared in the in vitro liver model. This is likely the reason why the promising in vitro activity did not translate into in vivo activity on S. haematobium. This limitation could not be overcome by the formulation of lipid nanocapsules as a way to improve the in vivo activity. Further studies should focus on increasing the compound's bioavailability, to reach an active concentration in the microenvironment of the parasite.

Antinociception induced by artemisinin nanocapsule in a model of postoperative pain via spinal TLR4 inhibition.

Artemisinin (ART) was initially described for the control of inflammation and pain. However, the mechanisms involved with its antinociceptive effect are still poorly understood. Thus, this present study aimed to investigate the effect of ART in both free and nanocapsulated form on postoperative pain, as well as the participation of the spinal Toll-like receptor 4 (TLR4) in this process. Postoperative pain was induced using the skin/muscle incision retraction (SMIR) model in male Swiss mice. After 3 and 28days of SMIR, the animals received an intrathecal injection of free or nanocapsulated ART, and the nociceptive threshold was evaluated by von Frey filament test. To evaluate the involvement of the microglia, astrocytes, and TLR4, minocycline (a microglia inhibitor), fluorocitrate (an astrocyte inhibitor), and Lipopolysaccharide Rhodobacter sphaeroides (LPS-RS), a TLR4 antagonist, were intrathecally injected on the third day of SMIR. The levels of spinal TLR4 protein and proinflammatory cytokines tumor necrosis factor-alpha (TNF-α), and interleukin-1-beta (IL-1β) were quantified by western blot and enzyme-linked immunosorbent assay, respectively. The results showed that free ART reduced postoperative pain (P < 0.001, F5,30 = 7.49, 16.66% for 1000ng dose; and P < 0.01, F5,30 = 7.49, 14.58% for 500ng dose) on the 3rd day of SMIR; while the ART nanocapsule had this effect on both the third (P < 0.001; F5,30 = 4.94; 43.75, 39.58 and 72.91% for the 250, 500 and 1000ng doses, respectively) and 28th (P < 0.05; F5,30 = 7.71; 29.16 and 33.33% for the 500 and 1000ng doses, respectively) day. The ART nanocapsule had a more potent and longer antinociceptive effect than free ART or morphine. Postoperative pain was also reduced by minocycline and LPS-RS. The ART nanocapsule also reduced the increased levels of TLR4, TNF-α, and IL-1β induced by SMIR. These data suggest that the ART nanocapsule has a potent analgesic effect on postoperative pain at the spinal level, and this response involves the inhibition of TLR4 and the proinflammatory cytokines TNF-α and IL-1β.

Full Factorial Design and Optimization of Olmesartan Medoxomil–Loaded Oily-Core Polymeric Nanocapsules with Improved In-Vitro Stability

This study aims to design oily-core nanocapsules for poorly water-soluble antihypertensive drug olmesartan medoxomil (OM) and optimize systematically the in-vitro characteristics of prepared nanosystems. The study represents an organized methodology for screening and studying significant parameters affecting polymeric nanocapsule formulation and characterization. A full two-level (23) factorial design was conducted to optimize the characteristics of poly-Ɛ-caprolactone oily-core nanocapsules (ONC) which were prepared using interfacial deposition of preformed polymer technique. The selected independent variables were the concentration of polymer, aqueous/organic phase ratio, and magnetic stirring rate. The selected formulation and processing variables significantly affected the tested responses. The developed ONC formulae showed a particle size (PS) range from 180.63 ± 0.31 to 338.93 ± 0.42 nm, polydispersity index values (PDI) were < 0.5, negative zeta potential (ZP) values from 20.17 ± 0.21 to 32.83 ± 0.21 mV, and entrapment efficiency (EE) values range from 74.63 ± 0.15 to 93.37 ± 0.15%. In-vitro drug release testing showed a controlled release pattern for OM over 8 h following Hixson-Crowell model for the optimized formula. Transmission electron micrographs (TEM) showed a perfect spherical nanocapsule with a clear polymeric coat. Stability study for 3 months at refrigerated and room temperatures showed non-significant variations and excellent stability for the prepared colloidal nanocapsular dispersion in terms of particle size (PS), zeta potential (ZP), polydispersity index (PDI), and entrapment efficiency (EE). It is concluded that ONC are such a promising nanosystem which can significantly improve the biopharmaceutical behavior of OM.

Formulation of parenteral nutrition based on argan oil nanocapsule system using d-optimal mixture design

In parenteral nutrition, the lipid emulsions are usually presented separately from other components. The admixture is made just before or during administration because of limited stability. The purpose of the present study is the formulation of lipid nanocapsules (LNC) based on Argan-oil and their introduction into preparations for parenteral nutrition, then the evaluation of their stability. The lipid nanocapsules have been prepared according to the phase inversion temperature method. The experimental design was used to determine the feasibility of LNC with Argan oil (A.O.-LNC), the evaluation of their size and the stability in the final mixing parenteral nutrition. The average size of the LNC was chosen as a response. The LNC based on 14% Argan oil, 6% Labrafac ®, 55% water and 25% of Solutol ® with an average size of 44 nm was selected for the preparation of the parenteral nutrition. The particle size distribution with a value of 70 nm and a polydispersity index of 0.102 indicates the homogeneity of the populations of particles. The statistical analysis shows the excellent stability of parenteral nutrition for 14 days.

Cytotoxic activity of poly-ɛ-caprolactone lipid-core nanocapsules loaded with lycopene-rich extract from red guava (Psidium guajava L.) on breast cancer cells

The aims of this study were to produce poly-ɛ-caprolactone lipid-core nanocapsules containing lycopene-rich extract from red guava (LEG), to characterize those nanoparticles and to evaluate their cytotoxic effects on human breast cancer cells. Lipid-core nanocapsules containing the extract (nanoLEG) were produced by the method of interfacial deposition of the preformed polymer. The nanoparticles were characterized by Dynamic Light Scattering (DLS), Polydispersity Index, Zeta Potential, pH, Encapsulation Efficiency, Nanoparticle Tracking Analysis (NTA), Atomic Force Microscopy (AFM) and Transmission Electron Microscopy (TEM). Cell viability was evaluated by the MTT dye reduction method in the human breast cancer MCF-7 cell line and inhibition of ROS and NF-κB was assayed in living human microglial cell line (HMC3) by time-lapse images microscopy. A hemolytic activity assay was carried out with sheep blood. Data showed that nanoparticles average size was around 200 nm, nanoparticles concentration/mL was around 0.1 µM, negative zeta potential, pH < 5.0 and spherical shape, with low variation during a long storage period (7 months) at 5 °C, indicating stability of the system and protection against lycopene degradation. The percentage of encapsulation varied from 95% to 98%. The nanoLEG particles significantly reduced the viability of the MCF-7 cells after 24 h (61.47%) and 72 h (55.96%) of exposure, even at the lowest concentration tested (6.25–200 μg/ml) and improved on the cytotoxicity of free LEG to MCF-7. NanoLEG inhibited LPS-induced NF-kB activation and ROS production in microglial cells. The particles did not affect the membrane integrity of sheep blood erythrocytes at the concentrations tested (6.25–200 μg/mL). Thus, the formulation of lipid-core nanocapsules with a polysorbate 80-coated poly-ɛ-caprolactone wall was efficiently applied to stabilize the lycopene-rich extract from red guava, generating a product with satisfactory physico-chemical and biological properties for application as health-promoting nanotechnology-based nutraceutical, emphasizing its potential to be used as a cancer treatment.

Preparation and characterization of lamotrigine containing nanocapsules for nasal administration

Nanocapsules (NCs) have become one of the most researched nanostructured drug delivery systems due to their advantageous properties and versatility. NCs can enhance the bioavailabiliy of hydrophobic drugs by impoving their solubility and permeability. Also, they can protect these active pharmaceutical agents (APIs) from the physiological environment with preventing e.g. the enzymatic degradation. NCs can be used for many administration routes: e.g. oral, dermal, nasal and ocular formulations are exisiting in liquid and solid forms. The nose is one of the most interesting alternative drug administration route, because local, systemic and direct central nervous system (CNS) delivery can be achived; this could be utilized in the therapy of CNS diseases. Therefore, the goal of this study was to design, prepare and investigate a novel, lamotrigin containing NC formulation for nasal administration. The determination of micrometric parameters (particle size, polydispersity index, surface charge), in vitro (drug loading capacity, release and permeability investigations) and in vivo characterization of the formulations were performed in the study. The results indicate that the formulation could be a promising alternative of lamotrigine (LAM) as the NCs were around 305 nm size with high encapsulation efficiency (58.44%). Moreover, the LAM showed rapid and high release from the NCs in vitro and considerable penetration to the brain tissues was observed during the in vivo study.

Design of dye and superparamagnetic iron oxide nanoparticle loaded lipid nanocapsules with dual detectability in vitro and in vivo.

Lipid nanocapsules are treasured nanoparticulate systems, although they lack detectability in biological environments. To overcome this, we designed LNCs loaded simultaneously with fluorescent dye and superparamagnetic iron oxide nanoparticles (Dual LNCs). The introduction of both labels did not alter nanoparticle characteristics such as size (50nm), size distribution (polydispersity index<0.1) or surface modifications, including the effectiveness of targeting ligands. Furthermore, the colloidal stability, particle integrity and biocompatibility of the nanoparticles were not negatively affected by label incorporation. These Dual LNCs are concomitantly visualizable via fluorescence and transmitted light imaging after either the internalization by cells or systemic administration to mice. Importantly, they are detectable in liver sections of mice using transmission electron microscopy without additional enhancement. The iron content of 0.24% (m/m) is sufficiently high for precise quantification of nanoparticle concentrations via inductively coupled plasma optical emission spectroscopy. Dual LNCs are precious tools for the investigation of in vitro and in vivo performances of lipid nanocapsule formulations, since they allow for the use of complementary imaging methods for broad range detectability.

Anthraquinone encapsulation into polymeric nanocapsules as a new drug from biotechnological origin designed for photodynamic therapy.

Photodynamic therapy has been applied for the treatment of many diseases, especially skin diseases. However, poor aqueous solubility and toxicity of some photosensitizer drugs are the main disadvantages for their direct clinical applications. Thus, biotechnology and nanotechnology are important tools in the development of new ways of obtaining photoactive compounds that are biocompatible. We investigated the potential of a new nanostructured photosensitizer, an anthraquinone derivative produced by biotechnological process; then we associated nanotechnology to obtain a nanostructured anthraquinone active molecule. For this, it was prepared a classical nanocapsule formulations containing poly(lactide-co-glycolide) (PLGA) coating for encapsulation of anthraquinone derivative. These formulations were characterized by their physicochemical, morphological, photophysical properties, and stability. We performed in vitro biocompatibility and photodynamic activity assays of free and nanostructured anthraquinone. Nanocapsule formulations containing anthraquinone derivative showed a nanometric profile with particle size around 250 nm, negative zeta potential around -30 mV, and partially monodisperse. Besides that, characteristic spherical morphology of nanocapsules and homogeneous particle surface were observed by AFM analyses. The in vitro biocompatibility assay showed absence of cytotoxicity for all tested RD/NC concentrations and also for unloaded/NC in NIH3T3 cells. In vitro photoactivation assay using NIH3T3 cells showed that nanocapsules promoted greater drug uptake by NIH3T3 cells, around of 87%, of cell death compared to free drug showed around 48% of cell death. The anthraquinone derivative showed potential for use in PDT. Besides the association with nanocapsules improved cell uptake of photosensitizer resulting in increased cell death compared to free anthraquinone.

Inhibition of colorectal cancer-associated fibroblasts by lipid nanocapsules loaded with acriflavine or paclitaxel.

Crosstalk between cancer-associated fibroblasts (CAFs) and colorectal cancer cells promotes tumor growth and contributes to chemoresistance. In this study, we assessed the sensitivity of a primary CAF cell line, CT5.3hTERT, to standard-of-care and alternative cytotoxic treatments. Paclitaxel (PTX) and acriflavine (ACF) were identified as the most promising molecules to inhibit CAF development. To allow the translational use of both drugs, we developed lipid nanocapsule (LNC) formulations for PTX and ACF. Finally, we mixed CAFs and tumor cell lines in a cocultured spheroid, and the effect of both drugs was investigated by histological analyses. We demonstrated CAF inhibition by LNC-ACF and whole tumor inhibition by LNC-PTX. Altogether, we proposed a new strategy to reduce CAF populations in the colorectal microenvironment that should be tested in vivo.

Intra-articular multifunctional celecoxib loaded hyaluronan nanocapsules for the suppression of inflammation in an osteoarthritic rat model

Direct intra-articular delivery of drugs to osteoarthritic joints offers the possibility of delivering high drug concentrations at the site of action as well as decreasing long term associated side effects after oral drug delivery. So in the current work, we aimed to improve the osteoarthritic therapeutic efficacy of the non-steroidal anti-inflammatory drug; celecoxib, through the formulation of drug loaded hyaluronan nanocapsules. The proposed formulation aimed to combine the beneficial viscosupplemental properties of hyaluronic acid with the pharmacological, anti-inflammatory, effect of celecoxib in a novel drug carrier for intra-articular delivery. The proposed nanocapsules were prepared by the nanoprecipitation method. Several formulation variables were studied aiming at optimizing the nanocapsules' size, polydispersity index and celecoxib entrapment efficiency %. The optimized hyaluronan nanocapsules formulation showed a size of 254.9±3.06nm, which is appropriate for the intra-articular delivery of celecoxib, high entrapment efficiency% of 97.98%±0.19, and prolonged celecoxib release for almost one week. The transmission electron microscope images revealed spherical shape of the nanocapsules with distinct shell and core structure. The in-vivo evaluation of the anti-osteoarthritic activity of the optimized hyaluronan nanocapsules formulation showed the superiority of the prepared celecoxib nanocapsules compared to celecoxib suspension in a Monoiodoacetate induced osteoarthritic rat model, regarding histological, swelling and immunohistochemical parameters of osteoarthritis.

Polymeric Nanocapsules as Nanotechnological Alternative for Drug Delivery System: Current Status, Challenges and Opportunities.

Polymer-based nanocapsules have been widely studied as a potential drug delivery system in recent years. Nanocapsules—as one of kind nanoparticle—provide a unique nanostructure, consisting of a liquid/solid core with a polymeric shell. This is of increasing interest in drug delivery applications. In this review, nanocapsules delivery systems studied in last decade are reviewed, along with nanocapsule formulation, characterizations of physical/chemical/biologic properties and applications. Furthermore, the challenges and opportunities of nanocapsules applications are also proposed.

Effects of resveratrol nanocapsules on the quantitative insulin sensitivity check index in insulin resistance: a study on metabolic syndrome induce mice

The aim of this study is to evaluate the effect of resveratrol nanocapsules (RV-NCs) by quantitative insulin sensitivity check index (QUICKI) for insulin resistance diagnosis on metabolic syndrome induction in mice. Next, the applicability of these nanocapsules (NCs) was evaluated in metabolic syndrome induced in 40 mice. RV-NCs were synthesized by interfacial deposition method and was analyzed by various methods including Zetasizer, high-performance liquid chromatograph, potentiometer and scanning electron microscopy. The analysis results show a zeta potential of − 7.15, loading efficiency of 99.54 ± 1.02% and particle size of 207 nm for RV-NC production. Collected data from mice examination were analyzed by ANOVA and Tukey criteria. The validity and the reproducibility of the QUICKI index in a population of mice were determined and found that is a significant difference between high fat diet group and the control group (p < 0.05). In addition, the result obtained by the Tukey test indicated the difference in insuline and glucose levels of these group. Also, it probably is associated with the increase in the in vivo stability, which is obtained by the effective formulation of nanocapsules for resveratrol delivery.

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.

Trazodone Loaded Lipid Core Poly (\u03b5-caprolactone) Nanocapsules: Development, Characterization and in Vivo Antidepressant Effect Evaluation

Trazodone hydrochloride (TRH) is a lipophilic drug which is used effectively as an antidepressant. Its poor solubility and short half-life represent an obstacle for its successful use. Nanocapsules with biodegradable polymeric shell are successful drug delivery systems for controlling the release of drugs. To enhance the entrapment of lipophilic drugs, oils can be added forming a lipophilic core in which the drug is more soluble. The aim of this study was to enhance the efficacy of TRH and prolong its action by formulating it into lipid core polymeric shell nanocapsules. Nanocapules were prepared using nanoprecipitation technique. All prepared formulations were in nano size range and negatively charged. The TRH entrapment efficiency (EE%) in lipid core nanocapsules was up to 74.8 ± 0.5% when using Labrafac lipophile as a lipid core compared to only 55.7 ± 0.9% in lipid free polymeric nanospheres. Controlled TRH release was achieved for all prepared formulations. Forced swim test results indicated the significant enhancement of antidepressant effect of the selected TRH loaded Labrafac lipophile core nanocapsules formulation compared to control and TRH dispersion in phosphate buffer. It is concluded that lipid core nanocapsules is a promising carrier for the enhancement of TRH efficacy.