Surface morphology and in vitro release performance of double-walled PLLA/PLGA microspheres entrapping a highly water-soluble drug

Double-walled microspheres trapping gentamicin sulphate were prepared from poly(l-lactic acid) (PLLA) and poly(l-lactic-co-glycolic acid) (PLGA) as a delivery system for highly hydrophilic antibiotics. The surface and cross-section morphology of the microspheres were characterized by SEM and FTIR. The diameters of the microspheres were ranging from about 50 μm to 700 μm. A low initial burst was achieved. The encapsulation efficiency was more than 70% and the cumulative drug release was about 40% for 30 days. The results indicated that the double-walled microspheres were able to achieve higher encapsulation efficiency and lower initial burst for highly water-soluble drugs.     

Formulation development and optimization of a novel Cremophore EL-based nanoemulsion using ultrasound cavitation

In the present study, response surface methodology (RSM) based on central composite design (CCD) was employed to investigate the influence of main emulsion composition variables, namely drug loading, oil content, emulsifier content as well as the effect of the ultrasonic operating parameters such as pre-mixing time, ultrasonic amplitude, and irradiation time on the properties of aspirin-loaded nanoemulsions. The two main emulsion properties studied as response variables were: mean droplet size and polydispersity index. The ultimate goal of the present work was to determine the optimum level of the six independent variables in which an optimal aspirin nanoemulsion with desirable properties could be produced. The response surface analysis results clearly showed that the variability of two responses could be depicted as a linear function of the content of main emulsion compositions and ultrasonic processing variables. In the present investigation, it is evidently shown that ultrasound cavitation is a powerful yet promising approach in the controlled production of aspirin nanoemulsions with smaller average droplet size in a range of 200-300 nm and with a polydispersity index (PDI) of about 0.30. This study proved that the use of low frequency ultrasound is of considerable importance in the controlled production of pharmaceutical nanoemulsions in the drug delivery system.     

Process optimization and stability of D-limonene-in-water nanoemulsions prepared by ultrasonic emulsification using response surface methodology

d-limonene in water nanoemulsion was prepared by ultrasonic emulsification using mixed surfactants of sorbitane trioleate and polyoxyethylene (20) oleyl ether. Investigation using response surface methodology revealed that 10% d-limonene nanoemulsions formed at S₀ ratio (d-limonene concentration to mixed surfactant concentration) 0.6-0.7 and applied power 18 W for 120 s had droplet size below 100 nm. The zeta potential of the nanoemulsion was approximately −20 mV at original pH 6.4, closed to zero around pH 4.0, and around −30 mV at pH 12.0. The main destabilization mechanism of the systems is Ostwald ripening. The ripening rate at 25 °C (0.39 m³ s⁻¹ × 10²⁹) was lower than that at 4 °C (1.44 m³ s⁻¹ × 10²⁹), which was in agreement with the Lifshitz-Slezov-Wagner (LSW) theory. Despite of Ostwald ripening, the droplet size of d-limonene nanoemulsion remained stable after 8 weeks of storage.     

Magnetic lipid nanoparticles loading doxorubicin for intracellular delivery: Preparation and characteristics

Tumor intracellular delivery is an effective route for targeting chemotherapy to enhance the curative effect and minimize the side effect of a drug. In this study, the magnetic lipid nanoparticles with an uptake ability by tumor cells were prepared dispersing ferroso-ferric oxide nanoparticles in aqueous phase using oleic acid (OA) as a dispersant, and following the solvent dispersion of lipid organic solution. The obtained nanoparticles with 200 nm volume average diameter and −30 mV surface zeta potential could be completely removed by external magnetic field from aqueous solution. Using doxorubicin (DOX) as a model drug, the drug-loaded magnetic lipid nanoparticles were investigated in detail, such as the effects of OA, drug and lipid content on volume average diameter, zeta potential, drug encapsulation efficiency, drug loading, and in vitro drug release. The drug loading capacity and encapsulation efficiency were enhanced with increasing drug or lipid content, reduced with increasing OA content. The in vitro drug release could be controlled by changing drug or lipid content. Cellular uptake by MCF-7 cells experiment presented the excellent internalization ability of the prepared magnetic lipid nanoparticles. These results evidenced that the present magnetic lipid nanoparticles have potential for targeting therapy of antitumor drugs.     

Preparation of magnetic polylactic acid microspheres and investigation of its releasing property for loading curcumin

In order to obtain a targeting drug carrier system, magnetic polylactic acid (PLA) microspheres loading curcumin were synthesized by the classical oil-in-water emulsion solvent-evaporation method. In the Fourier transform infrared spectra of microspheres, the present functional groups of PLA were all kept invariably. The morphology and size distribution of magnetic microspheres were observed with scanning electron microscopy and dynamic light scattering, respectively. The results showed that the microspheres were regularly spherical and the surface was smooth with a diameter of 0.55-0.75 μm. Magnetic Fe₃O₄ was loaded in PLA microspheres and the content of magnetic particles was 12 wt% through thermogravimetric analysis. The magnetic property of prepared microspheres was measured by vibrating sample magnetometer. The results showed that the magnetic microspheres exhibited typical superparamagnetic behavior and the saturated magnetization was 14.38 emu/g. Through analysis of differential scanning calorimetry, the curcumin was in an amorphous state in the magnetic microspheres. The drug loading, encapsulation efficiency and releasing properties of curcumin in vitro were also investigated by ultraviolet-visible spectrum analysis. The results showed that the drug loading and encapsulation efficiency were 8.0% and 24.2%, respectively. And curcumin was obviously slowly released because the cumulative release percentage of magnetic microspheres in the phosphate buffer (pH=7.4) solution was only 49.01% in 72 h, and the basic release of curcumin finished in 120 h.     

Quantitative ToF-SIMS studies of protein drug release from biodegradable polymer drug delivery membranes

Biodegradable polymers are of interest in developing strategies to control protein drug delivery. The protein that was used in this study is Keratinocyte Growth Factor (KGF) which is a protein involved in the re-epithelialization process. The protein is stabilized in the biodegradable polymer matrix during formulation and over the course of polymer degradation with the use of an ionic surfactant Aerosol-OT (AOT) which will encapsulate the protein in an aqueous environment. The release kinetics of the protein from the surface of these materials requires precise timing which is a crucial factor in the efficacy of this drug delivery system.Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used in the same capacity to identify the molecular ion peak of the surfactant and polymer and use this to determine surface concentration. In the polymer matrix, the surfactant molecular ion peak was observed in the positive and negative mode at m/z 467 and 421, respectively. These peaks were determined to be [AOT + Na⁺] and [AOT − Na⁺]. These methods are used to identify the surfactant and protein from the polymer matrix and are used to measure the rate of surface accumulation. The second step was to compare this accumulation rate with the release rate of the protein into an aqueous solution during the degradation of the biodegradable film. This rate is compared to that from fluorescence spectroscopy measurements using the protein autofluorescence from that released into aqueous solution [C.M. Mahoney, J. Yu, A. Fahey, J.A.J. Gardella, SIMS depth profiling of polymer blends with protein based drugs, Appl. Surf. Sci. 252 (2006), 6609-6614.].     

In vitro study of magnetic particle seeding for implant assisted-magnetic drug targeting

The concept of using magnetic particles (seeds) as the implant for implant assisted-magnetic drug targeting (IA-MDT) was analyzed in vitro. Since this MDT system is being explored for use in capillaries, a highly porous (ε∼70%), highly tortuous, cylindrical, polyethylene polymer was prepared to mimic capillary tissue, and the seeds (magnetite nanoparticles) were already fixed within. The well-dispersed seeds were used to enhance the capture of 0.87 μm diameter magnetic drug carrier particles (MDCPs) (polydivinylbenzene embedded with 24.8 wt% magnetite) under flow conditions typically found in capillary networks. The effects of the fluid velocity (0.015–0.15 cm/s), magnetic field strength (0.0–250 mT), porous polymer magnetite content (0–7 wt%) and MDCP concentration (C=5 and 50 mg/L) on the capture efficiency (CE) of the MDCPs were studied. In all cases, when the magnetic field was applied, compared to when it was not, large increases in CE resulted; the CE increased even further when the magnetite seeds were present. The CE increased with increases in the magnetic field strength, porous polymer magnetite content and MDCP concentration. It decreased only with increases in the fluid velocity. Large magnetic field strengths were not necessary to induce MDCP capture by the seeds. A few hundred mT was sufficient. Overall, this first in vitro study of the magnetic seeding concept for IA-MDT was very encouraging, because it proved that magnetic particle seeds could serve as an effective implant for MDT systems, especially under conditions found in capillaries.     

Continuous production of nanoemulsion for skincare product using a 3D-printed rotor-stator hydrodynamic cavitation reactor

In this study, nanoemulsions for skincare products were continuously produced using a hydrodynamic cavitation reactor (HCR) designed with a rotor and stator. The key component of this research is the utilization of a 3D-printed rotor in a HCR for the production of an oil-in-water nanoemulsion. Response surface methodology was used to determine the process conditions, such as speed of the rotor, flow rate, as well as, Span60, Tween60, and mineral oil concentrations, for generating the optimal droplet size in the nanoemulsion. The results showed that a droplet size of 366.4 nm was achieved under the recommended conditions of rotor speed of 3500 rpm, flow rate of 3.3 L/h, Span60 concentration of 2.36 wt%, Tween60 concentration of 3.00 wt%, and mineral oil concentration of 1.76 wt%. Moreover, the important characteristics for consideration in skincare products, such as polydispersity index, pH, zeta potential, viscosity, stability, and niacin released from formulations, were also assessed. For the niacin release profile of emulsion and nanoemulsion formulations, different methods, such as magnetic stirring, ultrasound, and hydrodynamic cavitation, were compared. The nanoemulsion formulations provided a greater cumulative release from the formulation than the emulsion. Particularly, the nanoemulsion generated using the HCR provided the largest cumulative release from the formulation after 12 h. Therefore, the present study suggests that nanoemulsions can be created by means of hydrodynamic cavitation, which reduces the droplet size, as compared to that generated using other techniques. The satisfactory results of this study indicate that the rotor-stator-type HCR is a potentially cost-effective technology for nanoemulsion production.     

Rotating magnetic macrospheres as heating mechanism for remote controlled drug release

A permanent magnetic macrosphere (diameter: 5 mm) spherically seated in an oil bearing inside an experimental capsule (comparable to a hard gelatine capsule size 2) is turned by a rotating magnetic field (H ? 5 kA/m; frequency ν?500 Hz) and causes a temperature rise up to about 60 °C. In order to find further possible improvements, the experimental results were compared to theoretical expectations. First experiments using improved thermal isolation yielded temperatures of about 100 °C. The heating can be used as a mechanism to remotely release drugs in the gastrointestinal tract.     

Low operating temperature of oxygen gas sensor based on undoped and Cr-doped ZnO films

Undoped and doped ZnO with 1 at.% (atomic percentage) chromium (Cr) was synthesized by RF reactive co-sputtering for oxygen gas sensing applications. The prepared films showed a highly c-oriented phase with a dominant (0 0 2) peak at a Bragg angle of around 34.2°. The operating temperature of the prepared ZnO sensor was around 350 °C and shifted to around 250 °C for the doped ZnO sensor which is lower than that of previously reported work. The sensitivity of the sensor toward oxygen gas was enhanced by doping ZnO with 1 at.% Cr. Good stability and repeatability of the sensor were demonstrated when tested under different concentration of oxygen atmosphere.     

Naproxen drug delivery using periodic mesoporous silica SBA-15

In this paper, we present the release of naproxen from hexagonal periodic mesoporous silica SBA-15, which serves as a drug delivery system. Naproxen, the well-known nonsteroidal anti-inflammatory drug (NSAID), was loaded into the pores of SBA-15 silica modified with aminopropyl groups. The physicochemical properties of the modified sample (A-SBA-15/napro) were compared with the unmodified SBA-15 mesoporous silica loaded with the drug (SBA-15/napro). The kinetic of the naproxen release into the physiological solution was studied. The released amount of naproxen represented 90.7% from the unmodified SBA-15 in 72 h, while from the sample A-SBA-15/napro the released amount represented about 80.9%. The prepared materials were characterized by nitrogen adsorption/desorption, Small angle X-ray scattering (SAXS), Fourier-transform infrared spectroscopy (FT-IR) and the thermoanalytical methods (TG/DTA). Thin layer chromatography (TLC) was used for quantitative determination of the released naproxen.     

In vitro study of magnetic nanoparticles as the implant for implant assisted magnetic drug targeting

Magnetic nanoparticle (MNP) seeds were studied in vitro for use as an implant in implant assisted-magnetic drug targeting (IA-MDT). The magnetite seeds were captured in a porous polymer, mimicking capillary tissue, with an external magnetic field (70 mT) and then used subsequently to capture magnetic drug carrier particles (MDCPs) (0.87 μm diameter) with the same magnetic field. The effects of the MNP seed diameter (10, 50 and 100 nm), MNP seed concentration (0.25-2.0 mg/mL), and fluid velocity (0.03-0.15 cm/s) on the capture efficiency (CE) of both the MNP seeds and the MDCPs were studied. The CE of the 10 nm MNP seeds was never more than 30%, while those of the 50 and 100 nm MNP seeds was always greater than 80% and in many cases exceeded 90%. Only the MNP seed concentration affected its CE. The 10 nm MNP seeds did not increase the MDCP CE over that obtained in the absence of the MNP seeds, while the 50 and 100 nm MNP seeds increased significantly, typically by more than a factor of two. The 50 and 100 nm MNP seeds also exhibited similar abilities to capture the MDCPs, with the MDCP CE always increasing with decreasing fluid velocity and generally increasing with increasing MNP seed concentration. The MNP seed size, magnetic properties, and capacity to self-agglomerate and form clusters were key properties that make them a viable implant in IA-MDT.     

Synthesis and characterization of polymeric nanospheres loaded with the anticancer drug paclitaxel and magnetic particles

We describe the preparation (by nanoprecipitation) and characterization of nanospheres (NPs) for magnetic drug targeting made of a magnetic fluid with poly(ethylene glycol), poly(d,l-lactic-co-glycolic acid) (PLGA), and the anticancer drug paclitaxel (Taxol^®). Infrared spectroscopy confirmed the incorporation of the drug in the PLGA NPs, which were also characterized in terms of morphology, size (typical diameter 200-250 nm) and colloidal stability in aqueous solutions of NaCl. Drug release and in vivo toxicity experiments of the prepared samples were performed. Their stability, magnetic properties (superparamagnetism), and lethal dose were found to be acceptable for the proposed application in cancer therapy.     

Fragrance release profile from sonochemically prepared protein microsphere containers

Protein microspheres have been prepared by sonicating a mixture of pure fragrant oil (amyl acetate (AA)) with an aqueous protein (bovine serum albumin) solution. The prepared protein spheres are nano- to micrometer sized with an encapsulation efficiency of approx. 97% for the AA present on the surface and inside the BSA capsule. Containers were found stable for more than 6 months when stored sealed at 4 °C and 20 °C. For the release profile measurements, we used a simple, automated and direct method. We continuously weighed the encapsulated microspheres and measured the evaporation rates. The release profiles at 15 °C and 25 °C display two different evaporation rates. The higher rate is the sum of a few evaporation rates, including water molecules, while the slower rate is due to the evaporation of pure AA. The changes in the evaporation rates occur upon the collapse of the container. This event coincides with the full evaporation of water. For morphological characterization we dyed the AA with Nile red, and used SEM, ESEM, Cryo-SEM, light microscopy, and confocal laser scanning microscopy measurements.     

Formulation development and evaluation of metronidazole magnetic nanosuspension as a magnetic-targeted and polymeric-controlled drug delivery system

A nanosuspension of magnetically tagged metronidazole was developed by the solvent displacement method coupled with ultrasonication and was evaluated for its physicochemical properties. The drug release from metronidazole magnetic nanosuspension at pH 1.2 and 7.0 shows maximum correlation coefficient for zero order and Higuchi model, respectively. The anthelmintic activity of the formulated metronidazole magnetic nanosuspension was evaluated on Indian earthworms (Pheretima poi). Metronidazole magnetic nanosuspension at a dose of 10 and 50 mg/ml shortened by 31% and 34%, respectively, the mean time to death of the earthworms when compared against a non-magnetic metronidazole suspension. Thus, the developed metronidazole magnetic nanosuspension showed potent, controlled and targeted drug action and might be a good therapeutic avenue in combating infectious GI disorders.     

Cross-linked gelatin/nanoparticles composite coating on micro-arc oxidation film for corrosion and drug release

A composite coating which could control drug release and biocorrosion of magnesium alloy stent materials WE42 was prepared. This composite coating was fabricated on the surface of the micro-arc oxidation (MAO) film of the magnesium alloy, WE42, by mixing different degrees of cross-linked gelatin with well-dispersed poly(dl-lactide-co-glycolide) (PLGA) nanoparticles. The PLGA nanoparticles were prepared by emulsion solvent evaporation/extraction technique. Nano ZS laser diffraction particle size analyzer detected that the size of the nanoparticles to be 150-300 nm. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) was used to analyze the morphology of the nanoparticles and the composite coating. Potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) were used to evaluate the corrosion behavior of the composite coating. Drug release was determined by ultraviolet-visible (UV-vis) spectrophotometer. The corrosion resistance of the composite coating was improved by preventing the corrosive ions from diffusing to the MAO films. The drug release rate of paclitaxel (PTX) exhibited a nearly linear sustained-release profile with no significant burst releases.     

Effect of dopant concentration on the properties of HCl-doped PANI thin films prepared at different temperatures

Polyaniline thin film doped with hydrochloric acid (PANI-HCl) has been prepared by chemical oxidative polymerization at three different temperatures (4 °C, 13 °C and 31 °C) with two different dopant concentrations (1 M, 2 M). Fourier transform infrared spectroscopy indicated the presence of dopant and increase in degree of polymerization with decrease in temperature. X-ray diffraction revealed that all the films are of amorphous nature. Scanning electron microscopy showed fiber morphology with high dense inter-fiber fusion. Hall-effect analysis showed that appreciable increase in conductivity of the PANI-HCl films with 2 M-dopant concentration prepared at low temperatures (4 °C, 13 °C) occurs due to increase in carrier concentration. It also indicates the films as P-type semiconductors. UV–vis absorption spectra and photoluminescence spectra revealed that the role of dopant concentration is highly effective in the films prepared at low temperatures. High intense absorption cum emission peaks observed for the films with 2 M dopant concentration prepared at low temperatures is due to the decreased fiber diameter which increased the surface to volume ratio of the fibers and increased localized defect states. Photoluminescence spectra of the films excited using 300 nm show high intense emission peaks at 360 nm, 494 nm and a weak peak at 409 nm confirming the semiconductor nature.     

Sorption and decomposition of crude oil using exfoliated graphite/ZnO composites

Exfoliated graphite/ZnO composites (EG/ZnO) were prepared by impregnating expandable graphite with Zn(OH)₂, abruptly expanding at 700 °C for 40 s, and heating at 500 °C for 3 h. The composites were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), nitrogen adsorption and mercury porosimetry. The sorption capacity of the composites for spilled crude oil was measured and under UV irradiation the decomposition of the absorbed crude oil was investigated. The results showed that the composites provided with the adsorption and photocatalysis capacity for crude oil at the same time. The sorption capacity of the composites decreased gradually on increasing the ZnO content of the composites. Moreover, the decomposition ratio of the absorbed crude oil increased on increasing the ZnO content or decreasing the weight ratio of crude oil to composites.     

Structure and stability characterization of pea protein isolate-xylan conjugate-stabilized nanoemulsions prepared using ultrasound homogenization

Preparation of pea protein isolate-xylan (PPI-X) conjugate-stabilized nanoemulsions using ultrasonic homogenization and the corresponding structure and environmental stability were investigated in this study. Conditions used to prepare nanoemulsions were optimized using a response surface methodology as follows: protein concentration 8.86 mg/mL, ultrasound amplitudes 57 % (370.5 W), and ultrasound time 16 min. PPI-X conjugate-stabilized nanoemulsions formed under these conditions exhibited less mean droplet size (189.4 ± 0.45 nm), more uniform droplet distribution, greater absolute value of zeta-potential (44.8 ± 0.22 mV), and higher protein adsorption content compared with PPI-stabilized nanoemulsions. PPI-X conjugate-stabilized nanoemulsions also exhibited even particle distribution and dense network structure, which might be reasons for the observed high interfacial protein adsorption content of conjugate-stabilized nanoemulsions. Moreover, better stability against environmental stresses, such as thermal treatment, freeze–thaw treatment, ionic strength and type, and storage time was also observed for the conjugate-stabilized nanoemulsions, indicating that this type of nanoemulsions possess a potential to endure harsh food processing conditions. Therefore, results provide a novel approach for the preparation of protein-polysaccharide conjugate-stabilized nanoemulsions to be applied as novel ingredients to meet special requirements of processed foods.     

Cellular uptake of folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles

We prepared five folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles (F₅-Liposuperparamagnetic iron oxide nanoparticles(SPIONs), 5.5 and 11 nm) and investigated their cellular uptake with KB cells, which is one of the representative folate-receptor over-expressing human epidermoid carcinoma cells, using MRI. The cellular uptake tests with the respective 5.5 and 11 nm F₅-LipoSPIONs at a fixed particle concentration showed appreciable amount of receptor-mediated uptakes and the specificity was higher in 5.5 nm SPIONs, due to its higher folic acid (FA) density, without inhibition. However, the numbers of the particles taken up under FA inhibition were similar, irrespective of their sizes.