Ethyl Cellulose Nanoparticles Research Articles

In vitro and in vivo evaluation of novel implantation technology in hydrogel contact lenses for controlled drug delivery

Glaucoma is commonly treated using eye drops, which is highly inefficient due to rapid clearance (low residence time) from ocular surface. Contact lenses are ideally suited for controlled drug delivery to cornea, but incorporation of any drug loaded particulate system (formulation) affect the optical and physical property of contact lenses. The objective of the present work was to implant timolol maleate (TM) loaded ethyl cellulose nanoparticle-laden ring in hydrogel contact lenses that could provide controlled drug delivery at therapeutic rates without compromising critical lens properties. TM-implant lenses were developed, by dispersing TM encapsulated ethyl cellulose nanoparticles in acrylate hydrogel (fabricated as ring implant) and implanted the same in hydrogel contact lenses (sandwich system). The TM-ethyl cellulose nanoparticles were prepared by double emulsion method at different ratios of TM to ethyl cellulose. The X-ray diffraction studies revealed the transformation of TM to amorphous state. In vitro release kinetic data showed sustained drug release within the therapeutic window for 168h (NP 1:3 batch) with 150μg loading. Cytotoxicity and ocular irritation study demonstrated the safety of TM-implant contact lenses. In vivo pharmacokinetic studies in rabbit tear fluid showed significant increase in mean residence time (MRT) and area under curve (AUC), with TM-implant contact lenses in comparison to eye drop therapy. In vivo pharmacodynamic data in rabbit model showed sustained reduction in intra ocular pressure for 192h. The study demonstrated the promising potential of implantation technology to treat glaucoma using contact lenses, and could serve as a platform for other ocular diseases.

Effects of Ionic Strength on the Colloidal Stability and Interfacial Assembly of Hydrophobic Ethyl Cellulose Nanoparticles.

Nanoparticle attachment at a fluid interface is a process that often takes place concurrently with nanoparticle aggregation in the bulk of the suspension. Here we investigate systematically the coupling of these processes with reference to the adsorption of aqueous suspensions of ethyl cellulose (EC) nanoparticles at the air-water interface. The suspension stability is optimal at neutral pH and in the absence of salt, conditions under which the electrostatic repulsion among EC nanoparticles is maximized. Nonetheless, hydrophobic attraction dominates particle-interface interactions, resulting in the irreversible adsorption of EC nanoparticles at the air-water interface. The addition of salt weakens the particle-particle and particle-interface repulsive electrostatic forces. This leads to destabilization of the suspension at ionic strengths of 0.05 M or greater but does not affect nanoparticle adsorption. The energy of adsorption, the surface tension and interface coverage at steady state, and the particle contact angle at the interface all remain unchanged by the addition of salt. These findings contribute to the fundamental understanding of colloidal systems and inform the utilization of EC nanocolloids, in particular for the stabilization of foams and emulsions.

Preparation, characterization and release kinetics of ethylcellulose nanoparticles encapsulating ethylvanillin as a model functional component

Food grade polymeric nanoparticles have the potential to play a key role in the future of active component delivery which is an essential characteristic of functional foods. For this potential to be realized, it is important to study both the loading and release characteristics of the encapsulated material from the particle matrix as a function of particle size, material properties and processing conditions. In this study, ethylcellulose nanoparticles encapsulating ethylvanillin as a model active component were prepared by electrohydrodynamic processing. The mean particle size varied between 45 and 85 nm and the polydispersity index between 16 and 34%. The loading capacity and encapsulation efficiency ranged between 67 and 81% and 71 and 84%, respectively. It was found that the release rate was a function of both the nanoparticle size and structure, and hence of the composition and processing conditions. FT-IR analysis demonstrated that there was no degradation of the encapsulated material during processing or whilst encapsulated within the particle. It was therefore concluded that electrohydrodynamic processing was a suitable method for producing nanoparticles that can be readily tailored for the encapsulation and controlled release of specific active components to engineer the functional characteristics of food products.

Silicone Surface with Drug Nanodepots for Medical Devices

An ideal surface of poly(dimethylsiloxane) (PDMS) medical devices requires sustained drug release to combat various tissue responses and infection. At present, a noncovalent surface coating with drug molecules using binders possesses a detachment problem, while covalently linking drug molecules to the surface provides no releasable drug. Here, a platform that allows the deposition of diverse drugs onto the PDMS surface in an adequate quantity with reliable attachment and a sustained-release character is demonstrated. First, a PDMS surface with carboxyl functionality (PDMS-COOH) is generated by subjecting a PDMS piece to an oxygen plasma treatment to obtain silanol moieties on its surface, then condensing the silanols with (3-aminopropyl)triethoxysilane molecules to generate amino groups, and finally reacting the amino groups with succinic anhydride. The drug-loaded carriers with hydroxyl groups on their surface can then be esterified to PDMS-COOH, resulting in a PDMS surface covalently grafted with drug-filled nanocarriers so that the drugs inside the securely grafted carriers can be released. Demonstrated here is the covalent linking of the surface of a PDMS endotracheal tube with budesonide-loaded ethylcellulose nanoparticles. A secure and high drug accumulation at the surface of the tubes (0.025 mg/cm2) can be achieved without changes in its bulk property such as hardness (Shore-A), and sustained release of budesonide with a high release flux during the first week followed by a reduced release flux over the subsequent 3 weeks can be obtained. In addition, the grafted tube possesses more hydrophilic surface and thus is more tissue-compatible. The grafted PDMS pieces show a reduced in vitro inflammation in cell culture and a lower level of in vivo tissue responses, including a reduced level of inflammation, compared to the unmodified PDMS pieces, when implanted in rats. Although demonstrated with budesonide and a PDMS endotracheal tube, this platform of grafting a PDMS surface with drug-loaded particles can be applied to other drugs and other devices.

Cellular trafficking and anticancer activity of Garcinia mangostana extract-encapsulated polymeric nanoparticles.

Garcinia mangostana Linn extract (GME) is a natural product that has received considerable attention in cancer therapy, and has the potential to reduce side effects of chemotherapeutics and improve efficacy. We formulated GME-encapsulated ethyl cellulose (GME-EC) and a polymer blend of ethyl cellulose and methyl cellulose (GME-EC/MC) nanoparticles. We achieved high drug-loading and encapsulation efficiency using a solvent-displacement method with particle sizes around 250 nm. Cellular uptake and accumulation of GME was higher for GME-encapsulated nanoparticles compared to free GME. In vitro cytotoxicity analysis showed effective anticancer activity of GME-EC and GME-EC/MC nanoparticles in HeLa cells in a dose-dependent manner. GME-EC/MC nanoparticles showed approximately twofold-higher anticancer activity compared to GME-EC nanoparticles, likely due to their enhanced bioavailability. GME-encapsulated nanoparticles primarily entered HeLa cells by clathrin-mediated endocytosis and trafficked through the endolysosomal pathway. As far as we know, this is the first report on the cellular uptake and intracellular trafficking mechanism of drug-loaded cellulose-based nanoparticles. In summary, encapsulation of GME using cellulose-derivative nanoparticles – GME-EC and GME-EC/MC nanoparticles – successfully improved the bioavailability of GME in aqueous solution, enhanced cellular uptake, and displayed effective anticancer activity.

Ethylcellulose nanoparticles with bimodal size distribution as precursors for the production of very small nanoparticles

A common technique for the preparation of polymeric nanoparticles (NPs) from preformed polymers is the emulsification solvent evaporation (ESE) method. However, the particle size of such carriers can typically not reduced below 100 nm. A bimodal distribution of particle size when applying ESE to the preparation of ethylcellulose (EC) NPs was intended to obtain very small particles in a size range below 50 nm. The proportion and size of the small particle fraction (SPF) depended on the surfactant as well as on the EC type and concentration. The preparation was conducted with different pharmaceutically relevant surfactants (polyoxyethylene (23) lauryl ether, sodium dodecyl sulfate, cetyltrimethylammonium bromide, polyvinyl alcohol and polysorbate 20) and all permitted obtaining very small NPs. After purification from excess surfactant by diafiltration and separation of the SPF by centrifugation, monodispersed particles with mean sizes between 20.6 ± 2.3 nm and 49.7 ± 4.8 nm could be isolated. The entrapment of a lipophilic model drug led to encapsulation rates between 34.0 ± 2.4% and 78.2 ± 12.6%, which were size and surfactant dependent. The preparation of polymeric NPs in a size below 50 nm by a simple centrifugation step holds promise for therapeutic applications where larger particles would be inefficient.

Ethyl cellulose nanoparticles: Clarithomycin encapsulation and eradication of H. pylori

The extreme acidic environment of the stomach, its regular voidance of contents and the restricted access to the mucus covered habitat combined with the antibiotic resistance of the bacteria, all contribute to the poor success in the treatment of Helicobacter pylori gastric infections. Here, we demonstrate that by encapsulating clarithromycin into ethyl cellulose (EC) nanoparticles, the efficiency of H. pylori clearance in C57BL/6 mice infected with these bacteria was significantly improved. Clarithomycin-loaded EC nanoparticles were prepared via a simple yet effective anti-solvent particle induction method, to yield sub-micron sized particles with 22.3±0.17% (w/w) clarithromycin loading at 86±0.5% (w/w) encapsulation efficiency. The particles dispersed well in water and simulated gastric fluid and gave a minimum inhibitory concentration of 0.09–0.18μg/ml against four strains of H. pylori. Encapsulation into EC particles not only enhanced the anti-adhesion activity of clarithromycin when tested with H. pylori and Hep-2 cells, but also gave significant enhancement of H. pylori clearance in the stomach of C57BL/6 mice infected with the bacteria.

UV protective textiles by the deposition of functional ethylcellulose nanoparticles

Ethylcellulose (EC) nanoparticles have been widely investigated for their use as drug delivery systems. However, their application on the textile field has been hardly studied. In this work, the use of EC nanoparticles as nanocarriers of active or lipid soluble compounds and their subsequent deposition on cotton textile is proposed in order to obtain functional textiles. A UV protective textile has been obtained after deposition of EC nanoparticles loaded with a liposoluble UV filter on cotton fabrics. The EC/cotton affinity and the attachment mechanism of EC nanoparticles on cotton substrate was studied by means of thermal behaviour evaluation, estimation of adhesion work (WA) and wash resistance tests. It is proposed that during EC nanoparticles deposition on cotton fabric, entanglement of polymeric chains is favoured, thus improving adhesion of EC nanoparticles on cotton substrate. The functionality of cotton textile was assessed by ultraviolet protection factor (UPF) measurements, showing a high UPF value (UPF = 45). Evaluation of UPF as a function of washing cycles were carried out on treated cotton fabrics. Washed fabrics still provided good UV protection (UPF ≥ 25), evidencing the presence of nanoparticles after washing cycles and the durability of the conferred functionality.

Irreversible Adsorption-Driven Assembly of Nanoparticles at Fluid Interfaces Revealed by a Dynamic Surface Tension Probe

Adsorption-driven self-assembly of nanoparticles at fluid interfaces is a promising bottom-up approach for the preparation of advanced functional materials and devices. Full realization of its potential requires quantitative understanding of the parameters controlling the self-assembly, the structure of nanoparticles at the interface, the barrier properties of the assembly, and the rate of particle attachment. We argue that models of dynamic surface or interfacial tension (DST) appropriate for molecular species break down when the adsorption energy greatly exceeds the mean energy of thermal fluctuations and validate alternative models extending the application of generalized random sequential adsorption theory to nanoparticle adsorption at fluid interfaces. Using a model colloidal system of hydrophobic, charge-stabilized ethyl cellulose nanoparticles at neutral pH, we demonstrate the potential of DST measurements to reveal information on the energy of adsorption, the adsorption rate constant, and the energy of particle-interface interaction at different degrees of nanoparticle coverage of the interface. These findings have significant implications for the quantitative description of nanoparticle adsorption at fluid interfaces.

Preparation and characterization of repaglinide loaded ethylcellulose nanoparticles by solvent diffusion technique using high pressure homogenizer

ObjectiveAn oral hypoglycemic agent repaglinide has less bioavailability and half-life. Its repeated dosing may cause side effects like headache, skeletal muscle pain and gastrointestinal effects. To overcome these problems, a sustained release nanoparticles has designed to maintain constant level of a drug in the patient's blood stream. Materials and methodsThe sustained released nanoparticles were prepared by Solvent emulsion diffusion technique using ethylcellulose as carrying material. Drug and polymer at different ratios were dissolved in ethyl acetate. To reduce size high pressure homogenizer was used. Final freeze dried nanoparticles used for characterization. ResultsThe obtained nanoparticles sizes 90.48 nm, 148.4 nm, 240.7 nm were increased in order of polymer concentrations. There encapsulation efficiency was up to 97.66 ± 0.88% in higher drug-polymer ratio. Infrared spectroscopy proved that there was not interaction between repaglinide and ethylcellulose. X-ray diffraction observed the crystallinity of recovered nanoparticles was less than pure repaglinide. The obtained nanoparticles sustained 11.24 ± 0.06 to 18.32 ± 0.12% repaglinide up to 12 h. The mechanism of drug release was Anomalous/non-Fickian diffusion. ConclusionSaturated ethylcellulose ethyl acetate solution facilitates efficient encapsulation of repaglinide at 0.5% PVA. The drug release mechanism is combination of diffusion and erosion. This formulation can increase patient compliance by reduce the number of dosage and incidence of side effects.

Continuous Generation of Ethyl Cellulose Drug Delivery Nanocarriers from Microbubbles

To investigate a new microfluidic method for the continuous preparation of hollow-shell nanoparticles of a hydrophobic polymer and the simultaneous encapsulation within these of a hydrophilic active pharmaceutical ingredient. A specially designed and constructed microfluidic device which facilitates at a junction the impingement of two liquids flowing in capillaries kept 60° apart, one containing the polymer ethyl cellulose (EC) and the other active pharmaceutical ingredient amoxicillin, and a gas flowing in a capillary bisecting the two liquid flows, was used to continuously generate EC coated microbubbles at an outlet directly below the gas flow. The bubbles produce EC nanoparticles whilst encapsulating amoxicillin, and these were characterised by microscopy, zeta potential measurements, FTIR and UV spectroscopy and in vitro drug release and kinetic studies. The device produced ~5 × 10(6) microbubbles per minute from the surface of which EC nanocarriers were released spontaneously according to an evaporation-controlled mechanism. The gas pressure was very effective in controlling the size and size distribution of the nanocarriers. Nanocarriers with diameter between 10 and 800 nm were continuously produced by controlling the gas pressure between 110 and 510 kPa. Depending on their size, particles were capable of encapsulating 65-88% of amoxicillin which was released over ~12 h.

Improvement of fatigue resistance of spirooxazine in ethyl cellulose and poly(methyl methacrylate) nanoparticles using a hindered amine light stabilizer

Abstract A spirooxazine dye has been doped in poly(methyl methacrylate) and ethyl cellulose nanoparticles by emulsion-solvent evaporation method. Tinuvin 144 hindered amine light stabilizer with an antioxidant moiety was selected as an efficient photostabilizer for improving the fatigue resistance of the two nanocomposite systems. Entrapment of the stabilizer practically did not increase the size of nanocapsules, however, the duration of the decolouration was enhanced significantly in both poly(methyl methacrylate) and ethyl cellulose, but more substantially in the former one. The half-life of spirooxazine in dichloromethane solution as well as in suspensions of poly(methyl methacrylate) and ethyl cellulose was 0.9 h, 8.4 h and 9.6 h, respectively. Considerable enhancement of fatigue resistance of Tinuvin 144 containing poly(methyl methacrylate)–spirooxazine (half-life: 35.0 h) and ethyl cellulose–spirooxazine nanocomposite (half-life: 14.8 h) was measured related to the corresponding photochromic nanocomposites without photostabilizer.

Development of a Novel and Customizable Two-Solution Mixing Type Spray Nozzle for One-Step Preparation of Nanoparticle-Containing Microparticles

Production of drug nanoparticles is an effective strategy to enhance solubility and oral absorption of water-insoluble drugs. The handling of drug nanoparticles has been an important issue in drug formulation because nanoparticles easily aggregate each other and redispersion of these particles is very difficult. In the present study, we developed a unique two-solution mixing type spray nozzle that can prepare drug nanoparticles in microparticles in one step without any common solvent and surfactant, and then, the prepared formulation were evaluated. Ethylcellulose (EC) and mannitol (MAN) were used as a model polymer of water-insoluble compound and a water-soluble carrier, respectively. We characterized the EC/MAN microparticles produced by the novel spray nozzle when customizing the nozzle parts to mix EC and MAN solution. Relatively smaller EC nanoparticles (<110 nm) in MAN microparticles (approximately 3 µm) were obtained by changing the customizable parts in the nozzle. In addition, the core of EC nanoparticles (<50 nm) was also observed by atomic force microscopy. We also found that the mixing time in the nozzle parts affected the size and the standard deviation of EC nanoparticles. These results suggest that the size of EC nanoparticles in MAN microparticles is controllable by using this unique nozzle. After all, we could prepare MAN microparticles containing EC nanoparticles in one step by using the novel nozzle. The drug/MAN microparticles formulation produced by the nozzle may be useful for the handling of drug nanoparticles.

Functionalized derivatives of 1,4-dimethylnaphthalene as precursors for biomedical applications: synthesis, structures, spectroscopy and photochemical activation in the presence of dioxygen

Decomposition of endoperoxide containing molecules is an attractive approach for the delayed release of singlet oxygen under mild reaction conditions. Here we describe a new method for the adaptation of the corresponding decay times by controlling the supramolecular functional structure of the surrounding matrix in the immediate vicinity of embedded singlet oxygen precursors. Thus, a significant prolongation of the lifetime of the endoperoxide species is possible by raising the energy barrier of the thermal (1)O(2)-releasing step via a restriction of the free volume of the applied carrier material. Enabling such a prolonged decomposition period is crucial for potential biomedical applications of endoperoxide containing molecules, since sufficient time for appropriate cell uptake and transport to the desired target region must be available under physiological conditions before the tissue damaging-power of the reactive oxygen species formed is completely exhausted. Two novel polyaromatic systems for the intermediate storage and transport of endoperoxides and the controlled release of singlet oxygen in the context of anticancer and antibiotic activity have been prepared and characterized. These compounds are based on functionalized derivatives of the 1,4-dimethylnaphthalene family which are readily forming metastable endoperoxide species in the presence of dioxygen, a photosensitizer molecule such as methylene blue and visible light. In contrast to previously known systems of similar photoreactivity, the endoperoxide carrying molecules have been designed with optimized molecular properties in terms of potential chemotherapeutic applications. These include modifications of polarity to improve their incorporation into various biocompatible carrier materials, the introduction of hydrogen bonding motifs to additionally influence the endoperoxide decay kinetics, and the synthesis of bifunctional derivatives to enable synergistic effects of multiple singlet oxygen binding sites with an enhanced local concentration of reactive species. With these compounds, a promising degree of endoperoxide stability adjustment within the carrier matrix has been achieved (polymer films or nanoparticles), which now opens the stage for appropriate targeting of the corresponding pro-drugs into live cells. First results on cytocidal and cytostatic properties of these compounds embedded in ethylcellulose nanoparticles are presented. Furthermore, an efficient low-cost method for the photochemical production of reactive endoperoxides based on high-power 660 nm LED excitation at room temperature and ambient conditions in ethanol solution is reported.

Highly fluorescent ethyl cellulose nanoparticles containing embedded semiconductor nanocrystals

Highly luminescent organic nanoparticles were formed by embedding hydrophobic and hydrophilic (CdSe)ZnS quantum dots with core/shell structure into ethyl cellulose nanoparticles. The nanoparticles were prepared from oil-in-water nanoemulsions by a phase inversion process at constant temperature, followed by a solvent evaporation. The obtained fluorescent ethyl cellulose nanoparticles were functionalized by immobilization of a specific antibody, and applied in rapid agglutination test for detection of Yersinia pestis F1-antigen.

Preparation of ethyl cellulose nanoparticles from nano-emulsion obtained by inversion at constant temperature

A new method for the preparation of nanoparticles from nano-emulsions using a low- energy emulsification method based on phase inversion at constant temperature (catastrophic inversion) is described. This method does not require any special equipment such as high-pressure homogenisers. The method is demonstrated for the preparation of ethyl cellulose nanoparticles containing pyrene (a microviscosity and micropolarity probe) as a hydrophobic model molecule. The nano-emulsions were prepared using a combination of non-ionic surfactants: Polyglycerol fatty acid ester (decaglycerol mono laurate) and sorbitan ester (Span 20), volatile organic solvent (toluene) and ethyl cellulose. Toluene was evaporated from the nano-emulsions, resulting in ethyl cellulose nanoparticles 50-120 nm in size. The emission colours of the pyrene-embedded nano-emulsions changed from blue to violet after the evaporation of the toluene because of the absence of excimers. This method may be applied for the preparation of a variety of polymeric nanoparticles in which functional molecules are embedded within the particles.

Indomethacin polymeric nanosuspensions prepared by microfujidization

Polymeric nanosuspensions containing indomethacin were prepared by a microfluidization-solvent evaporation method. The nanosuspensions were evaluated with respect to total drug content, drug content in the polymer and aqueous phase, particle size, drug crystallization in the aqueous phase, in vitro drug release, and stability to flocculation in 0.1 N HCl and pH 7.4 phosphate buffer. Nanosuspensions with a total drug content of 35 mg indomethacin/ml nanosuspension could be prepared without drug crystallization. More than 98% of the drug were found within the polymer phase. Unwanted drug crystallization in the aqueous phase depended on the drug loading, the drug-polymer compatibility, the organic solvent, and the type and amount of surfactant used. Indomethacin was released rapidly from ethyl cellulose nanoparticles within 15 minutes. Nanoparticles intended to provide drug release over longer periods of time were obtained by using mixtures of ethyl cellulose and poly (methyl methacrylate). In pH 7.4 buffer, anionic, nonionic and macromolecular stabilizers protected the nanosuspensions against flocculation while nonionic surf octants were good stabilizers in 0.1 N HCl.