Development of industrially feasible concentrated 30% and 40% nanoemulsions for intravenous drug delivery

Emulsions for parenteral nutrition loaded with drugs are used for optimized drug delivery, but in case of poorly oil soluble drugs, the injection volume can be too large when using commercial 10–20% oil emulsions. To reduce the injection volume, the feasibility of producing injectable, physically stable concentrated emulsions up to 40% oil content was investigated. Emulsions were made from fish oil, stabilized with egg lecithin, using high-pressure homogenization. Emulsions with oil contents of 10%–40% were investigated to assess basic correlations between increasing oil content, applied production pressures, homogenization cycles and resulting bulk droplet size, content of larger particles, zeta potential, viscosity and short-term stability. The observed correlations showed that in high-pressure homogenization, the contribution of the dispersive effect dominated the coalescence effect at low and Optimum production conditions for 30% and 40% nanoemulsions, i.e. 800 bar and 2 -3 homogenization cycles, were established on lab scale. These production conditions are industrially feasible. The obtained droplet sizes (about 200?nm) and the content of larger droplets were comparable to 10% commercial emulsions of parenteral nutrition, being important for in vivo tolerability and organ distribution. Despite the high oil concentration, the viscosity of the nanoemulsions was sufficiently low for injection. The short-term storage study showed physical stability for 1 month. A concentrated nanoemulsion base formulation from regulatory accepted excipients is now available, ready for loading with drugs.     

Fabrication of nanoporous Sr incorporated TiO2 coating on 316L SS: Evaluation of bioactivity and corrosion protection

In this paper, nanoporous TiO₂ and Sr-incorporated TiO₂ coated 316L SS were prepared by sol–gel methodology. The effect of Sr incorporation into TiO₂ coating on bioactivity and corrosion resistance was investigated. Attenuated total reflectance–Fourier transform infrared (ATR–FTIR) spectroscopy, X-ray diffraction analysis (XRD), atomic force microscopy (AFM), scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) results obtained after in vitro bioactivity test confirm the excellent growth of crystalline hydroxyapatite (HAp) over nanoporous Sr-incorporated TiO₂ coated 316L SS which may be attributed to the slow and steady release of Sr ions from the coatings. The electrochemical evaluation of the coatings confirms that Sr-incorporated TiO₂ coating offer excellent protection to 316L SS by acting as a barrier layer. The results showed that the incorporation of Sr enhanced both bioactivity and corrosion resistance of 316L SS. Hence Sr-incorporated TiO₂ coated 316L SS is a promising material for orthopaedic implant applications.     

Crystalline and amorphous carvedilol-loaded nanoemulsions: formulation optimisation using response surface methodology

This study aimed to evaluate the crystalline and amorphous carvedilol along with their lipidic mixtures using various instrumental techniques and to use response surface methodology in conjunction with factorial design to establish the functional relationships between operating variables (capmul GMS 50?K and cremophor RH 40).

The response variables selected are spectroscopic absorbance (Y ₁), mean particle size in distilled water (Y ₂) and in phosphate buffer pH 6.8 (Y ₃), polydispersibility index (PDI) (Y ₄) and zeta potential (Y ₅).

The optimal formulations of crystalline and amorphous carvedilol-loaded nanoemulsions were composed of fixed levels, ?0.41 and ?0.42, of capmul GMS 50?K and cremophor RH 40, respectively. The predicted and observed values of Y ₁–Y ₅ for blank nanoemulsions showed the percentage bias error of ?12.12%, ?10.25%, ?18.47%, +14.81 and ?2.89, respectively. The bias percent ranged between ?2.70% and ?29.41% for the responses Y ₁–Y ₄ for both crystalline and amorphous carvedilol-loaded nanoemulsions, indicating high degree of prognosis. However, the bias percent values for the response variable Y ₅ were 294.2% and 262.6%, for the crystalline and amorphous carvedilol-loaded nanoemulsions, respectively, possibly due to cationisation of emulsion droplets. The transmission electron microscopy of selected optimal nanoemulsions showed the spherical shape of globules with no signs of coalescence and precipitation of drug.

This study demonstrates the use of factorial design for the preparation of nanoemulsions of crystalline and amorphous carvedilol. The desirable goals can be obtained by systematic formulation approach in the shortest possible time.     

Jaboticaba (Plinia peruviana) extract nanoemulsions: development,stability, and in vitro antioxidant activity

Objective: The aim of this work is to develop and characterize nanoemulsions containing jaboticaba extract (Plinia peruviana) aiming pharmaceutical and cosmetic applications.

Methods: Nanoemulsions were prepared by high-pressure homogenization method using different concentrations of components (oil, surfactant, and extract) and homogenization pressures, in order to optimize the preparation conditions. Both unloaded and extract-loaded nanoemulsions were characterized according to their size, polydispersity, zeta potential, pH, morphology, and physical stability. Total phenolic and flavonoid contents in free jaboticaba extract and jaboticaba-loaded nanoemulsions were determined spectrophotometrically, while ellagic acid content was determined by high-performance liquid chromatography (HPLC) analysis. In vitro antioxidant activity was investigated by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) methods.

Results: Colloidal dispersions exhibited a mean particle size around 200?nm, with monodisperse size distribution (PdI <0.3), and spherical shape. Stability studies showed that nanoemulsions were stable over 120?d of storage at room temperature. Jaboticaba nanoemulsions showed significant concentrations of phenolics, flavonoids, and ellagic acid, with encapsulation efficiency values higher than 90%. Antioxidant properties of jaboticaba nanoemulsions were demonstrated by its remarkable ability to scavenge DPPH free radicals and to reduce ferric–tripyridyltriazine complex, which can be attributed to their phenolic and flavonoid contents.

Conclusions: The results suggest that nanoemulsions containing jaboticaba extract can be considered a promising candidate as a new antioxidant agent.     

Deposition of TiO2 nano-particles on wood surfaces for UV and moisture protection

Deposition of TiO₂ nanoparticles on wood surface was realised to improve the wood stability against ultraviolet (UV) light and moisture degradation. Photocatalytic activity of TiO₂ nanoparticles was utilised for protection of the wood surface. TiO₂ nano-particles were achieved by a sol–gel deposition method using EtOH/TiCl4 solution. Dip-coating process and subsequent annealing were used to realise nano-particles on wood surface. This method of deposition was utilised for the conformal covering of the wood structure as demonstrated by morphological investigation of the prepared samples by field emission scanning electron microscopy. Colour change measurements and Fourier transform infrared spectroscopy were used to analyse the lignin and carbonyl degradation of uncoated and coated wood during the UV exposure. Moisture protection of the coated wood was investigated by measuring the contact angle of the distilled water and wood surface. The measurements showed the UV and moisture protection of the TiO₂ layer.     

Synthesis and characterization of photocatalytic polyurethane and poly(methyl methacrylate) microcapsules for the controlled release of methotrexate

Abstract

The aim of this work is to prepare ultraviolet (UV) triggered controlled release of compounds from microcapsule systems (MCs). Polyurethane (PU) and poly(methyl methacrylate) (PMMA) microcapsules were studied with/without chemical functionalization using photocatalytic TiO₂ nanoparticles (NPs) on their surface. Once TiO₂ nanoparticles are illuminated with UV light (λ?=?370?nm), they initiate the rupture of the polymeric bonds of the microcapsule and subsequently initiate the encapsulated compound release, methotrexate (MTX) or rhodamine (Rh), in the present work. The size, polydispersity, charge, and yield of all MCs were measured, being the methotrexate drug release for all systems determined and compared with and without functionalization with TiO₂ NPs, under dark, visible light and UV illumination in vitro. Finally, the Rh release was characterized using fluorescence microscopy. The TiO₂ NPs size is around 10?nm, as determined by X-ray diffraction experiments. The PU MCs average size is around 60?µm, its electric charge +3.11?mV and yield around 85%. As for the PMMA MCs, the average size is around 280?µm, its electric charge ?7.2?mV and yield around 25% and 30% for both MTX and Rh, respectively. In general, adding TiO₂ NPs or the encapsulated products to the MCs does not affect the size but functionalization with TiO₂ NPs lowers the electric charge. Microcapsules functionalized with TiO₂ nanoparticles and irradiated with UV light presented the highest release of MTX and Rh. All other samples showed lower drug release levels when studied under the same conditions.     

Influence of lipid microparticle encapsulation on in vitro efficacy,photostability and water resistance of the sunscreen agents,octyl methoxycinnamate and butyl methoxydibenzoylmethane

Context: Essential requirements for the efficacy of sunscreen agents are optimal UV absorption, high photostability and resistance against water removal.

Objective: Aim of this study was to investigate the effect of encapsulation in lipid microparticles (LMs) on the overall performance of the two most commonly used sunscreen agents, octyl methoxycinnamate (OMC) and butyl methoxydibenzoylmethane (BMDBM).

Methods: LMs loaded with OMC and BMDBM were prepared by melt emulsification and characterized by optical microscopy, UV filter content and release studies. The LMs incorporating OMC and BMDBM or the nonencapsulated sunscreen agents were introduced into a model cream (oil-in-water emulsion).

Results: No significant differences were observed between the sun protection factor (SPF) of the formulations containing the free (SPF, 9.4?±?1.9) or microencapsulated (SPF, 9.6?±?1.3) UV filters. Irradiation of the creams with a solar simulator demonstrated that the photodecomposition of OMC and BMDBM was significantly decreased by encapsulation in LMs from 55.7?±?5.3% to 46.1?±?5.1% and 36.3?±?3.9% to 20.1?±?4.7%, respectively. However, in vitro water-resistance studies showed that entrapment in the LMs significantly enhanced the sunscreen agent removal caused by watering (the losses for OMC and BMDBM were 45.1?±?6.3% and 49.2?±?8.4%, respectively), as compared to the formulation with the nonencapsulated sunscreen agents (the losses for OMC and BMDBM were 26.7?±?6.1% and 28.0?±?6.7%, respectively).

Conclusion: Incorporation in LMs can have controversial effects on UV filter efficacy. In particular, the water-resistance properties of sun-care formulations containing sunscreens loaded in LMs should be verified to assure that the photoprotective activity is maintained during usage.     

Diffusion mechanism and release profile of a multivitamin from TiO2 hollow particles

The present study aimed to control the release rate profile of a multivitamin that has hydrophilic and hydrophobic properties and to investigate its diffusion rate from titanium dioxide (TiO₂) hollow particles. The TiO₂ hollow particles encapsulating the vitamins C and E were prepared via a sol-gel process using an inkjet nozzle. The obtained particles were evaluated by scanning electron microscopy and energy dispersive X-ray spectroscopy. The sustained release rate was estimated by the dialysis bag method. Additionally, a diffusion mechanism for the multivitamin from the TiO₂ hollow particles was proposed.TiO₂ particles prepared by this method exhibited spherical porous structures. The TiO₂ hollow particles were successful in encapsulating both the hydrophilic vitamin C and the hydrophobic vitamin E, resulting in a sustained release profile for these two components from the TiO₂ hollow particles. The release behavior of the multivitamin was quite different from that of each single vitamin. This is related to the adsorption state of each vitamin on the TiO₂ particle surface. The effective diffusion coefficient of VC derivative (8.403 × 10⁻¹³ cm²/s) was faster than that of VE derivative (1.671 × 10⁻¹³ cm²/s). This tendency may be attributed to the difference between hydrophilic and hydrophobic properties. Additionally, the value of effective diffusion coefficient in multi-component was always larger than that in single component. The value of Knudsen diffusion coefficient in VC and VE derivative was 2.684 × 10⁻³ and 2.264 × 10⁻³ cm²/s, respectively. In all samples, Knudsen diffusion coefficient was larger than molecular diffusion coefficient. The diffusion mechanism of the active ingredients likely depends on the pore size of TiO₂ and the molecular size of the active ingredients.     

Ultrasound-Responsive Microneedles Eradicate Deep-Layered Wound Biofilm Based on TiO2 Crystal Phase Engineering

Wound biofilm infection has an inherent resistance to antibiotics, requiring physical debridement combined with chemical reagents or antibiotics in clinical treatment, but it is invasive and may exist as incomplete debridement. So, a new type of noninvasive and efficient treatment is needed to address this problem. Here, the crystal phase engineering of TiO₂ is presented to explore the sonocatalytic properties of TiO₂ nanoparticles with different phases, and find that the anatase-brookite TiO₂ (AB) has the best antibacterial efficiency of 99.94% against S. aureus under 15 min of ultrasound (US) irradiation. The type II homojunction of AB not only enhances the adsorption and decreases the activation energy of O₂, respectively, but also has a great interfacial charge transfer efficiency under US, which can produce more reactive oxygen species than other types of TiO₂. The microneedles (MN) penetrate the biofilm in wound tissue and quickly disperse the loaded AB into the biofilm because the ultrasonic cavitation accelerates the dissolution of microneedles, which non-invasively and efficiently eradicates the deep-layered biofilm under US. This work explores the relationship between the phase composition of TiO₂ and sonocatalytic property for the first time, and provides a new treatment strategy for wound biofilm infection through US-assisted microneedles therapy.     

Fabrication of carbon-core/TiO2-sheath nanofibers by carbonization of poly(vinyl alcohol)/TiO2 composite nanofibers prepared via electrospinning and an interfacial sol–gel reaction

Carbon-core/TiO₂-sheath nanofibers have been fabricated from poly(vinyl alcohol) (PVA)/TiO₂ composite nanofibers that were prepared by electrospinning an aqueous solution of PVA and introducing the thread-like droplets directly into a titanium tetraisopropoxide (TTIP)/heptane solution. The PVA/TiO₂ composite nanofibers were transformed into carbon/TiO₂ nanofibers by iodine vapor treatment at 353 K, which induced dehydration of PVA, followed by carbonization in N₂ at 873 K. The carbon/TiO₂ nanofibers had diameters of a few hundred nanometers and sheathes of tens of nanometers. The nanofibers were composed of carbon cores with a low degree of graphitization and TiO₂ sheaths with an anatase crystal structure. The electrical conductivity of the carbon/TiO₂ composite nanofibers was enhanced by 4 orders of magnitude compared with TiO₂ hollow nanofibers.     

Nanoemulsions as delivery systems for lipophilic drugs

Nanoemulsions have received a growing attention as colloidal drug carriers for pharmaceutical applications. Their advantages over conventional formulations include drug enhanced solubility and bioavailability, protection from toxicity, improved pharmacological activity and stability, more sustained delivery and protection from physical and chemical degradation. Nanoemulsions can be prepared by two major techniques, high-energy and low-energy emulsification. Both these emulsification methods have proved to be efficient to obtain stable nanoemulsions with small and highly uniform droplets. Further research into nanoemulsions is important to develop novel liquid formulations with more efficient results in therapeutic.     

The superhydrophilicity of Al–TiO2 nanometer sized material synthesized using a solvothermal method

This study focuses on the surface properties of nano-sized Al–TiO₂ synthesized by a solvothermal method. The results indicate that the Al/TiO₂ particles, which are below 25 nm in size, exhibited a uniformly spherical anatase structure. The results of XRD and FT-Raman spectra showed that the Al ion was well incorporated into TiO₂ anatase framework. The Al-incorporated TiO₂ exhibited a larger (195–299 m²/g) area compared with that formed by pure TiO₂ (45 m²/g). In addition, the XPS spectra showed that Al–TiO₂ possessed a higher hydrophilic property than pure TiO₂ did. Consequently, these results of characterization supported our proposition that super-hydrophilicity was enhanced in Al–TiO₂ than that in pure TiO₂, it resulted from the contact angle below 1° for water droplets under 365 nm radiations.     

Development and characterization of repellent formulations based on nanostructured hydrogels

Abstract

Diseases caused by insects could lead to epidemic scenarios in urban areas and insect repellents are a shield against a wide range of insects, but they need to be safe without compromising efficacy. Ethyl butylacetylaminopropionate (EB) is a synthetic mosquito repellent, which could be used in products for adults and children due to its low-allergenic potential. The aim of this study was to develop and characterize EB and Poloxamer 407 nanoemulsions regarding their droplets mean size, pH, rheological properties, cytotoxicity and in vitro permeation profile. The developed formulations (F1 with 12.5% of EB and F2 with 25% of EB) were compared with a commercial formulation containing 12.5% of EB. Droplets mean size was determined by DLS, and for both nanoemulsions they were around 200?nm; however, the commercial formulation presented a droplets mean size of 10?nm, which could contribute to its high permeation. F1 and F2 presented a gel-like behavior, however F2 presented lower viscosity due to the presence of more EB between the polymer chains preventing them to interact with each other. Also, F2 was less retained by the epidermis when compared to F1 probably due to its lower viscosity. For the cytotoxicity assay only F2, which presented the highest concentration of EB was tested, and it was not toxic to the cells. This result could be also extended to F1 which presented half the EB concentration. The present study demonstrated that EB and Poloxamer 407 nanoemulsions are promising as new insect-repellent formulations.     

Preparation of TiO2 nanocapsules for loading and release of antimicrobial triclosan molecules

Well-defined nanosized hollow TiO₂ capsules with the diameter of 80-100 nm were prepared through aging dissolvation technique for the first time to remove the templates of core-shell composite spheres. The as-prepared TiO₂ nanocapsules were characterized by TEM. Furthermore, the antimicrobial triclosan was loaded into these nanocapsules. The loading of triclosan was determined by TGA-DTA, and the loading amount is about 29 wt.%. The release behavior of the entrapped triclosan molecular was investigated by UV-visible absorption (UV-vis). There is a moiety of triclosan that was loaded inside the TiO₂ shell. The results indicated that this drug release system has a sustained-release property. Such antimicrobial-loaded TiO₂ nanocapsules can be used as additive in household and personal care chemical industry.     

Sol–gel derived nickel-doped TiO2 films as wear protection coatings

Thin films of pure and Ni-doped TiO₂ were prepared on a glass substrate by sol–gel and spin-coating process from specially formulated ethanol sols. The morphologies of the films surface were observed with atomic force microscope (AFM). The tribological properties of the obtained thin films sliding against steel ball were evaluated on a one-way reciprocating friction tester. AFM results show that by the addition of the Ni in TiO₂, smooth surfaces were obtained. As a result, the Ni-doped TiO₂ films exhibit better wear protection properties than pure TiO₂. The best protection was observed for 5% Ni-doped TiO₂ films in this study.     

A new method for surface modification of TiO2/Al2O3 nanocomposites with enhanced anti-friction properties

In this paper, the TiO₂/Al₂O₃ composite nanoparticles were prepared by a hydrothermal method and in situ modified with acrylic acid. It was found that the mean particle size of modified TiO₂/Al₂O₃ composite nanoparticles was about 80 nm with a uniform distribution by the particle size analysis. The modified TiO₂/Al₂O₃ composite nanoparticles can disperse in lubricating oil homogenously for several weeks. The dispersion stabilization of modified TiO₂/Al₂O₃ composite nanoparticles in lubricating oil was significantly improved in comparison with the as-prepared nanoparticles, which was due to the introduction of grafted polymers by surface modification. The formation of covalent bands was identified by Fourier transform infrared spectrum. Under an optimized concentration of 0.1 wt%, the averaged friction coefficient was reduced by 14.75%, when the modified TiO₂/Al₂O₃ composite nanoparticles were used as lubricating oil additivities.     

Synthesis and characterization of insulin/zirconium phosphate@TiO2 hybrid composites for enhanced oral insulin delivery applications

Abstract

In this work, a series of composites of insulin (Ins)/zirconium phosphate (ZrP) were synthesized by intercalation method, then, these composites were coated with TiO₂ by sol-gel method to prepare Ins/ZrP@TiO₂ hybrid composites and the drug release of the composites was investigated by using UV-Vis spectroscopy. Ins/ZrP (10, 30, 60?wt%) composites were prepared by intercalation of insulin into the ZrP layers in water. Then Ins/ZrP composites were coated with different amounts of TiO₂ (30, 50, 100?wt %) by using titanium tetra n-butoxide, as precursor. Formation of intercalated Ins/ZrP and Ins/ZrP@TiO₂ hybrid composites was characterized by FT-IR, FE-SEM, BET and XRD analysis. Zeta potential of the optimized Ins/ZrP@TiO₂ hybrid composite was determined ?27.2?mV. Cytotoxic effects of the optimized Ins/ZrP@TiO₂ hybrid composite against HeLa and Hek293T cell lines were evaluated using MTT assay and the results showed that designed drug delivery system was not toxic in biological environment. Compared to the Ins/ZrP composites, incorporation of TiO₂ coating enhanced the drug entrapment considerably, and reduced the drug release. The Ins/ZrP composites without TiO₂ coating released the whole drug after 30?min in pH 7.4 (phosphate buffer solution) while the TiO₂-coated composites released the entrapped drug after 20?h. In addition to increasing the shelf life of hormone, this nanoencapsulation and nanocoating method can convert the insulin utilization from injection to oral and present a painless and more comfortable treatment for diabetics.     

A complex investigation of the nanofluids R600а-mineral oil-AL2O3 and R600а-mineral oil-TiO2. Thermophysical properties

This paper presents experimental data for the density, solubility, viscosity and capillary constant for solutions of the natural refrigerant isobutane (R600a) with mineral compressor oil and nanoparticles Al₂O₃ and TiO₂ over a wide range of temperatures and concentrations. Based on obtained information for the capillary constant, the surface tension of the solutions isobutane/mineral oil/Al₂O₃ nanoparticles and isobutane/mineral oil/TiO₂ nanoparticles is determined. SP-QSPR (Scaling Principles–Quantitative Structure Property Relationship) model has been successfully applied for fitting the experimental data obtained for solutions of isobutane with mineral compressor oil and nanoparticles Al₂O₃ and TiO₂. It was shown that the nanoparticle additives lead to increase of the viscosity and reduce surface tension of the refrigerant/oil solutions.     

An investigation on synthesis and magnetic properties of ferromagnetic nanoparticles of nickel ferrite coated with TiO2

TiO₂-coated nickel ferrite (NiFe₂O₄) nanoparticles were obtained by the hydrolysis of titanium tetrabutyloxide in the presence of NiFe₂O₄ nanoparticles in water/oil (w/o) microemulsion. The effects of TiO₂ coating on the magnetic properties of NiFe₂O₄ nanoparticles were investigated. The structural, morphological and magnetic properties of as-prepared samples were characterized by X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectra, transmission electron microscopy (TEM) and magnetic measurements. The morphology analysis confirmed that the obtained composite nanoparticles consisted of NiFe₂O₄ coated by TiO₂. It was shown that the saturation magnetization and coercivity of NiFe₂O₄ decreased after TiO₂ coating, which can be interpreted by the interparticle dipole–dipole interactions related to the magnetic particle volume fraction in the composite nanoparticles.     

Controllable fabrication of hollow TiO2 spheres as sustained release drug carrier

TiO₂ hollow spheres with controllable size were successfully synthesized through a hydrothermal silica etching method; SiO₂ cores were easily removed without the use of a toxic reagent. The parameters for the synthesis of SiO₂ cores and TiO₂ hollow spheres, including stirring time, ammonia concentration, tetrabutyl titanate content, hydrothermal time, and reflux time, were systematically investigated. SiO₂ cores and TiO₂ hollow structure were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), energy dispersive X-ray spectra (EDX), X-ray photoelectron spectroscopy (XPS), and N₂ adsorption-desorption isotherms. The results revealed that the mean diameter of SiO₂ was ∼280 nm when the concentration of ammonia was 4.8 M and the stirring time was 0.5 h. For hollow TiO₂, when the operation process was optimized (ammonia volume 0.35 mL, TBOT addition 1.5 mL, hydrothermal time 3 h, and reflux time 3 h), the average size and the shell thickness were 270 and 100 nm, respectively. The process exhibited a high drug loading capacity (33.12 ± 0.01%) and encapsulation rate (99.03 ± 0.24%) due to its high specific surface area of 121.62 m²·g⁻¹. In addition, TiO₂ hollow spheres displayed pH-responsive sustained-controlled drug release behavior in vitro which released 80% of doxorubicin at 5.0 pH within 120 h, its release kinetic showed that it fits well with Zero-order kinetic equation, demonstrating that DOX·HCl/hollow TiO₂ maintains constant release rate, and the investigation of blood compatibility showed that the hemolysis rate of hollow TiO₂ did not exceed 3% in the concentration range of 100 and 4000 μg/mL, further confirming that prepared hollow TiO₂ is a relatively safe medical inorganic material.