Ethyl Cellulose Nanoparticles Research Articles

Continuous preparation of sustained release vildagliptin nanoparticles using tubular microreactor approach

This investigation used a tubular microreactor to produce Vildagliptin (VLG) loaded ethyl cellulose (EC) nanoparticles (NPs) for sustained delivery of a drug. A central composite design was used to quantify the influence of independent variables on the desired responses. The independent factors selected to achieve the desired entrapment efficiency and sustained drug release were EC concentration and sodium lauryl sulfate concentration. On the other hand, the dependent variables chosen for assessment were particle size (Y1) and encapsulation efficiency (Y2). The nanoparticles produced were analyzed, which included particle size measurement, transmission electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, encapsulation efficiency (EE) determination, and in vitro drug release study. The optimized samples TEM investigation verified the nanoparticles’ spherical shape and particle size distribution, ranging from 160 to 250 nm. The entrapment efficiency (EE) fell within the range of 63–87%. In the in-vitro drug release study, VLG-loaded EC nanoparticles exhibited sustained release over 12 h. Applying various kinetic equations to the in-vitro drug release data demonstrated that the drug release mechanism involved diffusion. This comprehensive study concluded that the VLG-EC-NPs achieved optimal particle size, EE, and desirable level of sustained drug release.

Novel polymer composite coated with ethylcellulose nanoparticle from waste paper as an alternative material to extracorporeal oxygenation membrane

Extracorporeal membrane oxygenator (ECMO) is a valuable technology to support people with acute respiratory distress syndrome (ARDS) and is recommended for COVID-19 patients. This study aims to fabricate polymer-based composite membranes coated with ethylcellulose nanoparticles from waste paper and identify the performance of the composite as ECMO candidates. Composite membranes were made from four types of polymers, namely, nylon, PTFE (polytetrafluoroethylene), Pebax® MH-1657, and SBS (poly-(styrene-b-butadiene-b-styrene)). PDMS (polydimethylsiloxane) 1 wt.% and ethylcellulose nanoparticles (3% and 10 wt.%) were used as membrane coatings to increase their hydrophobic properties. The success of cellulose isolation and ethylcellulose synthesis from waste paper was confirmed by the FTIR and XRD analysis. The size of the synthesized ethylcellulose nanoparticles was 32.68 nm. The coating effect on composite membranes was studied by measuring the contact angle, membrane porosity, protein quantification tests, and single gas permeation of O2 and CO2. Based on the protein quantification test, the protein could not pass through the Pebax/PDMS and SBS/PDMS composites coated with 10 wt.% ethylcellulose; this indicated less risk of plasma leakage. The gas permeation test on nylon/PDMS, PTFE/PDMS, and SBS/PDMS composites coated with 10% ethylcellulose resulted high CO2/O2 selectivity, respectively, 2.17, 3.48, and 3.22 as good indication for extracorporeal oxygenation membrane.

Triboelectric Nanogenerators Based on Membranes Comprised of Polyurethane Fibers Loaded with Ethyl Cellulose and Barium Titanate Nanoparticles

High performance is always the research objective in developing triboelectric nanogenerators (TENGs) for future versatile applications. In this study, a flexible ethyl cellulose/thermoplastic polyurethane (EC/TPU) nanofiber triboelectric layer with barium titanate (BTO) nanoparticles is proposed for high-performance TENGs, in which electrospun EC/TPU nanofiber membranes supply the high-roughness friction surfaces and piezoelectric BTO nanoparticles are further incorporated to boost the electric outputs by the synergistic effect of piezoelectricity and triboelectricity. Consequently, when the content of the BTO nanoparticle is 8 wt % in the EC/TPU (1:4 in weight ratio) nanofibers, the composite membrane displayed a stress of 9.25 MPa and a strain of 275.2%. The corresponding TENG achieves electric outputs of 125.8 V, 34.1 μA, and 1.68 W/m2, much higher than those of an individual piezoelectric nanogenerator or TENG. The TENGs are potentially used to supply energy for commercial LEDs and microelectronics and as self-powered sensors to monitor human physical training conditions. This research provides a guideline for developing TENGs with high performance, which is crucial for their long-term use.

Enhanced freeze-thawing stability of water-in-oil Pickering emulsions stabilized by ethylcellulose nanoparticles and oleogels

This study developed water-in-oil (W/O) Pickering emulsions stabilized by ethylcellulose (EC) nanoparticles and EC oleogels, which presented significantly improved freeze-thawing (F/T) stability. Microstructural observation suggested EC nanoparticles were distributed at the interface and within the water droplets, and the EC oleogel trapped oil in the continuous phase. Freezing and melting temperatures of water in the emulsions with more EC nanoparticles were lowered and the corresponding enthalpy values were reduced. F/T led to lower water binding capacity but higher oil binding capacity of the emulsions, compared to the initial emulsions. Low field-nuclear magnetic resonance confirmed the increased mobility of water but decreased mobility of oil in the emulsions after F/T. Both linear and nonlinear rheological properties proved that emulsions exhibited higher strength and higher viscosity after F/T. The widened area of the elastic and viscous Lissajous plots with more nanoparticles suggested the viscosity and elasticity of emulsions were increased.

The Fundamental Role of Lipids in Polymeric Nanoparticles: Dermal Delivery and Anti-Inflammatory Activity of Cannabidiol.

This report presents a nanoparticulate platform for cannabidiol (CBD) for topical treatment of inflammatory conditions. We have previously shown that stabilizing lipids improve the encapsulation of CBD in ethyl cellulose nanoparticles. In this study, we examined CBD release, skin permeation, and the capability of lipid-stabilized nanoparticles (LSNs) to suppress the release of IL-6 and IL-8. The nanoparticles were stabilized with cetyl alcohol (CA), stearic acid (SA), lauric acid (LA), and an SA/LA eutectic combination (SALA). LSN size and concentration were measured and characterized by differential scanning calorimetry (DSC), in vitro release of loaded CBD, and skin permeability. IL-6 and IL-8 secretions from TNF-α-induced HaCaT cells were monitored following different LSN treatments. CBD released from the LSNs in dispersion at increasing concentrations of polysorbate 80 showed non-linear solubilization, which was explained by recurrent precipitation. A significant high release of CBD in a cell culture medium was shown from SALA-stabilized nanoparticles. Skin permeation was >30% lower from SA-stabilized nanoparticles compared to the other LSNs. Investigation of the CBD-loaded LSNs' effect on the release of IL-6 and IL-8 from TNF-α-induced HaCaT cells showed that nanoparticles stabilized with CA, LA, or SALA were similarly effective in suppressing cytokine release. The applicability of the CBD-loaded LSNs to treat topical inflammatory conditions has been supported by their dermal permeation and release inhibition of pro-inflammatory cytokines.

NIR Luminescent Oxygen-Sensing Nanoparticles for Continuous Glucose and Lactate Monitoring.

A highly sensitive, biocompatible, and scalable phosphorescent oxygen sensor formulation is designed and evaluated for use in continuous metabolite sensors for biological systems. Ethyl cellulose (EC) and polystyrene (PS) nanoparticles (NPs) stabilized with Pluronic F68 (PF 68), Polydimethylsiloxane-b-polyethyleneglycol methyl ether (PDMS-PEG), sodium dodecylsulfate (SDS), and cetyltimethylammonium bromide (CTAB) were prepared and studied. The resulting NPs with eight different surfactant−polymer matrix combinations were evaluated for physical properties, oxygen sensitivity, effect of changes in dispersion matrix, and cytotoxicity. The EC NPs exhibited a narrower size distribution and 40% higher sensitivity than PS, with Stern−Volmer constants (Ksv) 0.041−0.052 µM−1 for EC, compared to 0.029−0.034 µM−1 for PS. Notably, ethyl cellulose NPs protected with PF68 were selected as the preferred formulation, as they were not cytotoxic towards 3T3 fibroblasts and exhibited a wide phosphorescence lifetime response of >211.1 µs over 258−0 µM and ~100 µs over 2.58−0 µM oxygen, with a limit of detection (LoD) of oxygen in aqueous phase of 0.0016 µM. The EC-PF68 NPs were then efficiently encapsulated in alginate microparticles along with glucose oxidase (GOx) and catalase (CAT) to form phosphorescent nanoparticles-in-microparticle (NIMs) glucose sensing microdomains. The fabricated glucose sensors showed a sensitivity of 0.40 µs dL mg−1 with a dynamic phosphorescence lifetime range of 46.6−197.1 µs over 0−150 mg dL−1 glucose, with a glucose LoD of 18.3 mg dL−1 and maximum distinguishable concentration of 111.1 mg dL−1. Similarly, lactate sensors were prepared with NIMs microdomains containing lactate oxidase (LOx) and found to have a detection range of 0−14 mg dL−1 with LoD of 1.8 mg dL−1 and maximum concentration of 13.7 mg dL−1 with lactate sensitivity of 10.7 µs dL mg−1. Owing to its versatility, the proposed NIMs-based design can be extended to a wide range of metabolites and different oxygen-sensing dyes with different excitation wavelengths based on specific application.

Nanoparticle-Surfactant Stabilized Strong Foam for Enhanced Oil Recovery in High-Salinity Fractured Carbonate Reservoirs

Summary Foam flooding can minimize bypassing in gasfloods in fractured reservoirs. Finding a foam formulation effective in high-salinity brine is challenging, especially with divalent cations, e.g., American Petroleum Institute (API) brine (8% NaCl with 2% CaCl2). When formulating with nanoparticles, the colloidal dispersion stability is difficult due to the dramatic reduction in zeta potential and the Debye length at high salinity. The aim of this work was to develop a strong foam in API brine at the ambient temperature, using a nonionic surfactant and ethyl cellulose nanoparticles (ECNP), for gasflooding in fractured carbonate reservoirs. ECNPs was synthesized and dispersed in API brine using a nonionic surfactant (also denoted as SF). SF and SF/ECNP foams were generated, and their stability was studied at atmospheric pressure and 950 psi. Foam mobility was measured in a sandpack at high pressure. Foam flood experiments were conducted in oil-saturated fractured carbonate cores. The nonionic surfactant proved to be a good dispersion agent for ECNP in API brine. The SF/ECNP mixture stabilized foam in API brine, even in the presence of oil. Injecting a partially miscible gas (below its minimum miscibility pressure) as an SF foam into a fractured core more than doubles the oil recovery over injection of the gas alone. The injection of the strong foam (SF/ECNP) further improves the oil recovery over that of the SF foam, indicating the synergy between ECNP and surfactant. ECNP accumulates in the foam lamella and induces larger pressure gradients in the fracture to divert more gas into the matrix for oil displacement.

Ethyl cellulose nanoparticles as stabilizers for Pickering emulsions

Pickering emulsions stabilized by ethyl cellulose nanoparticles have recently received –great attention for their remarkable stability and numerous industrial applications. De- spite this, the exact stabilization mechanism of such Pickering emulsions is still not fully understood. Both the stabilization of the emulsion by particle adsorption at the inter- face and through network formation in the continuous phase (leading to a yield stress) have been suggested. In this work we study soybean oil-in-water emulsions stabilized by ethyl cellulose nanoparticles and find, by the use of confocal microscopy and interfa- cial tension measurements, that the main stabilization mechanism of this nanoparticle- stabilized emulsions is the adsorption of the particles at the interface, instead of forming a network in the continuous phase. At the same time, oscillatory rheology measurements reveal that the emulsions exhibit a yield stress well below the random close-packing limit for hard spheres, suggesting short-range interactions between the droplets caused by the presence of the particles at the interface. The presence of the particles at the interface in combination with the observed rheological behavior of an attractive emulsion gives a strong indication for a particle-bridged stabilized emulsions.

DEVELOPMENT OF NANO BASED FILM FORMING GEL FOR PROLONGED DERMAL DELIVERY OF LULICONAZOLE

Objective: Luliconazole (LZL) has low aqueous solubility that limits its dermal bioavailability and acts as a barrier to topical delivery. The conventional topical formulations have a limited ability to retain the drug over the skin for a prolonged period. The main objective of the study was to formulate and characterize LZL loaded ethyl cellulose (EC) nanoparticles and formulate them as a film-forming gel (FFG) for prolonged delivery in fungal skin infections.Methods: The solvent evaporation technique was used for the preparation of nanoparticles of LZL by using EC as a polymer. The prepared nanoparticles were evaluated for physical appearance, production yield, entrapment efficiency, drug content, particle size, zeta potential, Polydispersity index (PDI), and in vitro drug release. Then the nanoparticles were incorporated into FFG formulation by using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) as the gelling agent. The prepared FFG was evaluated for pH, Viscosity, Spreadability, in vitro drug release studies, in vitro antifungal studies, and release kinetic studies.Results: The optimized nanoparticle formulation F5 having drug to polymer ratio of 1:2 showed satisfactory production yield (86.32%), entrapment efficiency (83.36%), drug content (42.86), particle size (125.3), and 93.72% of in vitro drug release after 24 h (h). The optimized FFG formulation FFG4 showed the shortest film-forming time of 5.06 min (min), percentage Cumulative drug release of 92.18% after 24 h, and had promising in vitro antifungal activity.Conclusion: The prepared FFG could be used with promising potential for fungal infection of the skin.

W/O emulsions featuring ethylcellulose structuring in the water phase, interface and oil phase for multiple delivery

This study reported a novel approach to stabilize W/O emulsions with nanoparticles and oleogel from ethylcellulose (EC), and the emulsions were applied for multiple delivery. Microstructural observations revealed that EC nanoparticles were distributed within the water droplets and at the interface, and EC oleogel was in the continuous phase. Storage modulus and viscosity were higher, and thixotropic structural recovery rates were lower, in the emulsions with more EC nanoparticles. Both EC nanoparticles and oleogels worked to stabilized the emulsions upon freeze-thawing, as only minor water or oil was released. Upon heating, some EC nanoparticles transited from the interface to the oil phase, and water droplets were aggregated. The interface was recreated when the samples were re-emulsified. When curcumin and anthocyanin were incorporated, both bioactives had improved light stability. During in vitro study, curcumin was mostly released at the early stage of intestinal digestion, while anthocyanin was released at later stage.

Formulation and Optimization of Diclofenac Sodium Loaded Ethylcellulose Nanoparticles

Design of experiment (DoE) is a useful time and cost-effective tool for analyzing the effect of independent variables on the formulation characteristics. The aim of this study is to evaluate the effect of the process variables on the characteristics involved in the preparation of Diclofenac Sodium (DC) loaded ethylcellulose (EC) nanoparticles (NP) using Central Composite Design (CCD). NP were prepared by W/O/W emulsion solvent evaporation method. Three factors were investigated (DC/EC mass ratio, PVA concentration, homogenization speed) in order to optimize the entrapment efficiency (EE) and the particle size of NP. The optimal formulation was characterized by Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and in vitro release. Optimized formulation showed an EE of 49.09 % and an average particle size of 226.83 nm with a polydispersity index of 0.271. No drug-polymer interaction was observed in FTIR and DSC analysis. SEM images showed that the particles are spherical and uniform. The in vitro release study showed a sustained release nature, 53.98 % of the encapsulated drug has been released over 24hours period. This study demonstrated that statistical experimental design methodology can optimize the formulation and the process variables to achieve favorable responses.

Rheological and anti-microbial study of silica and silver nanoparticles-reinforced k-carrageenan/hydroxyethyl cellulose composites for food packaging applications

Sustainable food packaging films were developed using a combination of k-Carrageenan (k-C), hydroxyl ethyl cellulose (HEC), silicon dioxide (SiO2), and silver (Ag) nanoparticles. The CH-SiO2/Ag nanocomposites showed promising results, mainly due to their transparency, flexibility, low cost, and environmental friendliness. The structure and uniform morphology of the CH-SiO2/Ag nanocomposites were determined by FT-IR, XRD, and SEM analysis. Barrier properties (water vapor permeability-WVP), thermal properties (T5% loss, char yield), and mechanical properties determined for the k-C/HEC and k-C/HEC-SiO2/Ag nanocomposites, which improved by 3.3–1.9 × 10−9 gm/m2 Pa s (WVP), 59.1–115.7 °C (T5%), 13.4–29.3% (char yield), 23.8–41.5 MPa (tensile strength), and 22.3–28.9 (EB), respectively. The contact angle of the k-C/HEC-SiO2/Ag nanocomposites were in the range of 60.1°–76.4°. The UV transmittance of the k-C/HEC composites decreased with the addition of SiO2 and Ag nanoparticles. However, the transparency of the composites was not affected, and it inhibited UVA and UVB rays by the addition of Ag nanoparticles. The viscosity of the k-C/HEC composites increased with the SiO2 content and decreased with the shear rate. All the composites exhibited shear-thinning behavior. The storage modulus of the prepared composites is higher than the loss modulus in the entire frequency region. Overall, SiO2 and Ag nanoparticles improved the hydrophobic nature of the k-C/HEC-SiO2/Ag films and showed significant activity against six common food pathogens, Staphylococcus aureus, Bacillus cereus, Listeria monocytogenes, Bacillus subtilis, Salmonella typhi, and Cronobacter sakazakii. The synergistic combination of k-C/HEC-SiO2/Ag nanocomposite has potential candidate for packaging and other biomedical applications.

PH-responsive nanocarriers for combined chemotherapies: a new approach with old materials

Ethyl cellulose (EC) is widely used in the pharmaceutical field as a polymeric excipient to fabricate sustained-release drug delivery systems. To develop a controlled release carrier exploiting the unique characteristic acidic environment of the target tumor site, this study examined the use of EC and lecithin (LC) as a nanoparticulated system. Paclitaxel and dihydroartemisinin were used as model drug combinations. The optimized formulated nanoparticles (NPs) of EC (EC NPs) and EC/LC (EC/LC NPs) were spherical and approximately 130 nm in diameter as determined by dynamic light scattering and electron microscopy analyses. The in vitro drug release from EC/LC NPs exhibited a pH-dependent pattern. In in vitro cell studies, the NPs were taken up by cells, and cell growth was inhibited by drugs released from the formulations. Most importantly, the in vivo anti-tumor study in mice showed a significant reduction in tumor volume after the intravenous administration of EC/LC NPs, suggesting the potential of using EC and LC as controlled and pH-sensitive drug delivery carriers.

Improved Oil Recovery in Fractured Reservoirs by Strong Foams Stabilized by Nanoparticles

Enhanced oil recovery in fractured reservoirs is challenging because injected fluids flow mainly through the fractures without displacing oil from the matrix. Foam can enable injection into the matrix by creating a high pressure in the fractures. However, the foam has to be strong and stable in the presence of oil recovered from the matrix. This study focuses on developing a strong foam using nanoparticles and surfactants. Ethyl cellulose nanoparticles (ECNP) with a relatively narrow size distribution were prepared and dispersed in brine along with a nonionic surfactant (SF). The SF performed as both a nanoparticle dispersion agent and a foaming agent. The foam by ECNP/SF had better foamability and stability than the SF foam in the presence of oil. The mobility reduction factor of the ECNP/SF foam was 100 times larger than that of the SF foam and 3 times larger than an alpha olefin sulfonate (AOS) foam in a sand pack. Foam was injected into a fractured oil-wet Texas Cream limestone core saturated with oil. The oil recovery due to the ECNP/SF foam was significantly higher than those with only gas injection and conventional AOS foam injection. The novelty in this work lies in combining nanoparticles with surfactants to generate a strong foam which can be used to improve oil recovery from fractured, oil-wet reservoirs.

Enhancement of atorvastatin oral bioavailability via encapsulation in polymeric nanoparticles

Despite the fact that atrovastatin (At) is being one of the bestselling statins used to prevent complicated cardiovascular diseases, its low oral bioavailability decreases its clinical relevance. Herein, incorporation of At into ethylcellulose nanoparticles (At-NPs) was executed to test if it would enhance its oral bioavailability. The emulsification-evaporation method was used to prepare the At-NPs. The prepared nanoparticles were characterized by measuring the particle size, zeta potential as well as using FTIR, DSC, and XRD examination. The entrapment efficiency, drug content, and the in vitro release behavior of At-NPs were also examined. The in vivo oral bioavailability of the selected At-NPs formula was tested after being given orally to New Zealand rabbits. The nanoparticles obtained had a high drug content and a distinct spherical shape but with varying sizes. No physical or chemical interactions were detected between At and the nanoparticles as confirmed by FTIR, DSC, and XRD. The in vitro release study of At from the prepared At-NPs has shown nanoparticles size-dependent release behavior. The in vivo oral absorption testing confirmed the bioavailability of the prepared At-NPs to be as follows: (Cmax = 940 ng/ml and AUC0-12 = 8759 ng.h/ml) > Lipitor® (Cmax = 635 ng/ml and AUC0-12 = 4367 ng.h/ml) > At (Cmax = 515 ng/ml and AUC0-12 = 2517 ng.h/ml). These results revealed that the oral formula of At-NPs increases the bioavailability of At 3.87 times. This makes ethylcellulose nanoparticles an esteemed candidate nano-vehicle for At, increasing its bioavailability and thus improving its clinical relevance.

Ethylcellulose nanoparticles prepared from nano-emulsion templates as new folate binding haemocompatible platforms

Ethylcellulose is a biocompatible polymer attracting increasing interest for biomedical applications. In the present work, the formation of folate-ethylcellulose nanoparticle complexes from nano-emulsion templates prepared by a low-energy approach, using aqueous components suitable for biomedical applications has been investigated. The composition of the aqueous component is shown to be crucial for the formation of stable nano-emulsions and influences the zeta potential values. The ethylcellulose nanoparticles with mean sizes around 100 nm were obtained from the nano-emulsions by solvent evaporation and showed positive zeta potential values above +20 mV due to the presence of the cationic surfactant. The nanoparticles were successfully complexed with folate, as evidenced by both particle size and zeta potential measurements. The complexes prepared with HEPES buffered glucose solution showed excellent haemocompatibility, which make them promising for parenteral therapeutic applications and also for those in which easy access to systemic circulation may occur, like in lungs.

Preparation and characterization of dexamethasone polymeric nanoparticle by membrane emulsification method

The objective of this study was to prepare and characterize dexamethasone polymeric nanoparticles by membrane emulsification method. Shirasu porous glass was used as a membrane for the emulsification process. The mean particle size was determined by photon correlation spectroscopy, and the drug release test was performed in the dialysis cell. The size of nanoparticles was increased with increasing applied pressure, membrane pore size, the polymeric content of the oily phase, and oil/aqueous phase ratio and replacing chloroform with dichloromethane. As ethanol content in the organic solvent increased (0, 2.5, and 5% w/w), dexamethasone solubility was increased (0.35, 3.5, and 6.4 mg/g, respectively) with a minimal effect on the particle size. The agitation speed of 800 rpm is needed to ensure the oil phase-membrane detachment. Encapsulation efficiency was higher, and the drug release was faster from Eudragit® RL and RS nanoparticles than ethylcellulose nanoparticles. For polymeric nanoparticles, size differences have no impact on the drug release. It is concluded that the particle size could be controlled by an organic solvent and polymer type in addition to process parameters in the membrane emulsification technique. Additionally, zero-order release kinetic could be achieved from polymeric nanoparticles.

Production of antihyerglycemic and antihypertensive drug loaded sustained release nanoparticles using spray drying technique: Optimization by Placket Burman Design

Repaglinide (RPG, antidiabetic) and Diltiazem HCL (DIL, antihypertensive) loaded ethyl cellulose (EC) nanoparticles were prepared by the spray drying process using Placket Burman Design (PBD). The amount of EC (A, mg), Methanol (B, ml), Inlet temperature (C, OC), Feed rate (D, rpm), Nozzle diameter (E, mm) and Aspiration (F, rpm) were considered independent variables while EE of RPG (Y1) and EE of DIL (Y2) were selected as dependent variables. The optimized DIL and RPG loaded EC nanoparticles were further used for the development of oral fast disintegrating sustained release tablets by direct compression method. The tablets were evaluated for weight variation, thickness, hardness, disintegration time, friability and dissolution test. FTIR study showed no chemical interaction between drug and polymer. Scanning electron microscope showed spherical as well as oval shape and discrete nature of both nanoparticles. The physical parameters of oral fast disintegrating tablets developed with optimized formulation of drug loaded nanoparticles were found within the range. Drug loaded nanoparticles as well as oral fast disintegrating tablets showed very good sustained release behavior.

Neuroprotective effect of melatonin loaded in ethylcellulose nanoparticles applied topically in a retinal degeneration model in rabbits

We are reporting for the first time the synthesis and application of an innovative nanometric system for the controlled topic release of melatonin in the retina. The ethylcellulose nanocapsules were characterized by diverse physicochemical techniques (scanning electron microscopy, zeta potential, hydrodynamic diameters) and an in vitro release study was done. A complete ex vivo and in vivo trans-corneal permeation and an irritation study were carried out with the new formulations in albino rabbits, to which a retinal degenerative model was induced. The results obtained demonstrate that the in vitro release of melatonin (1 mg/mL and 2 mg/mL) transported by nanocapsules is slower when compared to a solution of melatonin. Greater penetration of melatonin through the cornea was demonstrated by ex vivo and in vivo tests. This can be attributable to an enhanced neuroprotective effect of melatonin on retinal ganglion cells when it is included in ethylcellulose nanocapsules compared to a solution of melatonin. These outstanding findings add promising new perspectives to current knowledge about administrations using nano-technological tools in the treatment of neurodegenerative diseases at the ocular level.

Amphotericin B loaded ethyl cellulose nanoparticles with magnified oral bioavailability for safe and effective treatment of fungal infection

Amphotericin B is a gold standard drug used in various fungal and parasitic infection treatment. Most of the marketed formulations are administered intravenously, but show dose-dependent adverse effects i.e., nephrotoxicity and hemolysis. Oral route eliminates the toxic concern but exhibits poor bioavailability. Therefore, ethylcellulose nanoparticles (EC-NPs) have been used for magnified oral delivery of AmB, where EC provides gastrointestinal stability. These nanoparticles were synthesized by high-pressure emulsification solvent evaporation (HPESE) method and evaluated for in vitro and in vivo studies. This method yields small, monodisperse AmB-EC-NPs along with smooth surface morphology and improved encapsulation efficiency. The developed formulation showed a sustained release pattern following Higuchi diffusion kinetics along with gastric and storage stability. Aggregation study revealed that AmB was present in its monomeric form inside the biocompatible EC matrix. The antifungal result demonstrated that the MIC of AmB-EC-NPs was reduced ∼1/3rd than AmB and Fungizone® at 24 h whereas it was observed ∼1/8th at 48 h. in vivo pharmacokinetic analysis demonstrated 1.3-fold higher AUC than Fungizone® even at a 4.5-time lesser dose via the oral route and a ∼15-fold rise in the bioavailability in contrast to the native AmB. The hemolytic study revealed that the developed formulation exhibited 8-fold lesser hemolysis than Fungizone®. Furthermore, the biosafety profile of AmB-EC-NPs was ensured by the significantly lesser level of blood urea nitrogen and plasma creatinine along with the normal pattern of renal tubules in comparison to AmB and Fungizone®. In conclusion, the results stipulated that the AmB-EC-NPs could be effective, viable and a better alternative to currently existing iv formulations, for magnified oral delivery of AmB in the treatment of fungal infection without associated adverse effects.