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Drug Delivery Dec 2021To overcome the shortcoming of conventional transarterial chemoembolization (cTACE) like high systemic release, a novel droplet-based flow-focusing microfluidic device...
To overcome the shortcoming of conventional transarterial chemoembolization (cTACE) like high systemic release, a novel droplet-based flow-focusing microfluidic device was fabricated and the biocompatible poly(lactic-co-glycolic acid) (PLGA) magnetic drug-eluting beads transarterial chemoembolization (TACE) microspheres with tunable size and shell thickness were prepared via this device. Paclitaxel, as a model active, was loaded through O/O/W emulsion method with high efficiency. The size and the shell thickness vary when adjusting the flow velocity and/or solution concentration, which caters for different clinical requirements to have different drug loading and release behavior. Under the designed experimental conditions, the average diameter of the microspheres is 60 ± 2 μm and the drug loading efficiency has reached 6%. The drug release behavior of the microspheres shows the combination of delayed release and smoothly sustained release profiles and the release kinetics differ within different shell thickness. The microspheres also own the potential of magnetic resonance imaging (MRI) visuality because of the loaded magnetic nanoparticles. The microsphere preparation method and device we proposed are simple, feasible, and effective, which have a good application prospect.
Topics: Antineoplastic Agents, Phytogenic; Chemistry, Pharmaceutical; Chemoembolization, Therapeutic; Drug Carriers; Drug Liberation; Emulsions; Humans; Magnetic Iron Oxide Nanoparticles; Microfluidics; Microspheres; Paclitaxel; Particle Size; Polylactic Acid-Polyglycolic Acid Copolymer
PubMed: 33818236
DOI: 10.1080/10717544.2021.1905739 -
Molecules (Basel, Switzerland) Jul 2022Drug delivery to the anterior or posterior segments of the eye is a major challenge due to the protection barriers and removal mechanisms associated with the unique...
Drug delivery to the anterior or posterior segments of the eye is a major challenge due to the protection barriers and removal mechanisms associated with the unique anatomical and physiological nature of the ocular system. The paper presents the preparation and characterization of drug-loaded polymeric particulated systems based on pre-emulsion coated with biodegradable polymers. Low molecular weight biopolymers (chitosan, sodium hyaluronate and heparin sodium) were selected due to their ability to attach polymer chains to the surface of the growing system. The particulated systems with dimensions of 190-270 nm and a zeta potential varying from -37 mV to +24 mV depending on the biopolymer charges have been obtained. Current studies show that particles release drugs (dexamethasone/pilocarpine/bevacizumab) in a safe and effective manner, maintaining therapeutic concentration for a longer period of time. An extensive modeling study was performed in order to evaluate the drug release profile from the prepared systems. In a multifractal paradigm of motion, nonlinear behaviors of a drug delivery system are analyzed in the fractal theory of motion, in order to correlate the drug structure with polymer. Then, the functionality of a SL(2R) type "hidden symmetry" implies, through a Riccati type gauge, different "synchronization modes" (period doubling, damped oscillations, quasi-periodicity and intermittency) during the drug release process. Among these, a special mode of Kink type, better reflects the empirical data. The fractal study indicated more complex interactions between the angiogenesis inhibitor Bevacizumab and polymeric structure.
Topics: Bevacizumab; Chitosan; Drug Carriers; Drug Delivery Systems; Drug Liberation; Emulsions; Nanoparticles; Particle Size; Polymers
PubMed: 35889383
DOI: 10.3390/molecules27144512 -
ACS Nano May 2022Herein, we present the direct observation and quantification of a water-in-oil (w/o) emulsion, its destabilization, and the effect of additives on such processes at the...
Herein, we present the direct observation and quantification of a water-in-oil (w/o) emulsion, its destabilization, and the effect of additives on such processes at the nanoscale. This is achieved liquid phase transmission electron microscopy (LPTEM), wherein a small volume of emulsion is encapsulated against vacuum in its liquid state to allow observation of its initial morphology and its evolution over time at excellent spatial and temporal resolution. Emulsions of this class are useful for delivering payloads of materials insoluble in their delivery medium and are currently widely used across food science, pharmaceuticals, and environmental applications. However, their utility is inherently limited by their thermodynamic tendency to demulsify, eventually leading to bulk phase separation. This occurs several degradation mechanisms, operating at times collectively, and which are difficult to differentiate traditional ensemble methods (, light scattering), obscuring mechanistic nuances. LPTEM as a characterization technique has the potential to augment our understanding of emulsion behavior and improve performance and formulations. In this work, we also emphasize the importance of the included videographic Supporting Information data in demonstrating the behavior of the studied materials.
Topics: Emulsions; Water; Drug Compounding; Thermodynamics
PubMed: 35302741
DOI: 10.1021/acsnano.2c00199 -
Applied Microbiology and Biotechnology May 2024The design, development, and obtaining of nanostructured materials, such as polymeric nanoparticles, have garnered interest due to loading therapeutic agents and its... (Review)
Review
The design, development, and obtaining of nanostructured materials, such as polymeric nanoparticles, have garnered interest due to loading therapeutic agents and its broad applicability. Polymeric nanoparticle synthesis employs advanced techniques such as the double emulsion approach and the pH-driven method, allowing the efficient incorporation of active compounds into these matrices. These loading methods ensure compound stability within the polymeric structure and enable control of the release of therapeutic agents. The ability of loaded polymeric nanoparticles to transport and release therapeutic agents on target manner represents a significant advancement in the quest for effective therapeutic solutions. Amid escalating concerns regarding antimicrobial resistance, interventions using polymeric nanostructures stand out for the possibility of carrying antimicrobial agents and enhancing antibacterial action against antibiotic-resistant bacteria, making a new therapeutic approach or complement to conventional treatments. In this sense, the capability of these polymeric nanoparticles to act against Escherichia coli underscores their relevance in controlling bacterial infections. This mini-review provides a comprehensive synthesis of promising techniques for loading therapeutic agents into polymeric nanoparticles highlighting methodologies and their implications, addressing prospects of combating bacterial infections caused by E. coli. KEY POINTS: • The double emulsion method provides control over size and release of bioactives. • The pH-driven method improves the solubility, stability, and release of active. • The methods increase the antibacterial action of those encapsulated in PNPs.
Topics: Anti-Bacterial Agents; Nanoparticles; Hydrogen-Ion Concentration; Emulsions; Polymers; Escherichia coli; Escherichia coli Infections; Biological Products
PubMed: 38819646
DOI: 10.1007/s00253-024-13114-5 -
Chemistry and Physics of Lipids Sep 20211,8-cineole is a monoterpene commonly used by the food, cosmetic, and pharmaceutical industries owing to its flavor and fragrances properties. In addition, this...
1,8-cineole is a monoterpene commonly used by the food, cosmetic, and pharmaceutical industries owing to its flavor and fragrances properties. In addition, this bioactive monoterpene has demonstrated bactericidal and fungicidal activities. However, such activities are limited due to its low aqueous solubility and stability. This study aimed to develop nanoemulsion containing cineole and assess its stability and antibacterial activity in this context. The spontaneous emulsification method was used to prepare nanoemulsion (NE) formulations (F1, F2, F3, F4, and F5). Following the development of NE formulations, we chose the F1 formulation that presented an average droplet size (in diameter) of about 100 nm with narrow size distribution (PdI <0.2) and negative zeta potential (∼ - 35 mV). According to the analytical centrifugation method with photometric detection, F1 and F5 formulations were considered the most stable NE with lower droplet migration velocities. In addition, F1 formulation showed high incorporation efficiency (> 80 %) and TEM analyses demonstrated nanosized oil droplets with irregular spherical shapes and without any aggregation tendency. Antibacterial activity assessment showed that F1 NE was able to enhance the cineole action against Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pyogenes. Therefore, using a simple and reproducible method of low energy emulsification we designed a stable nanoemulsion containing 1,8-cineole with improved antibacterial activity against Gram-positive strains.
Topics: Anti-Bacterial Agents; Drug Stability; Emulsions; Enterococcus faecalis; Eucalyptol; Microbial Sensitivity Tests; Nanostructures; Particle Size; Staphylococcus aureus
PubMed: 34216586
DOI: 10.1016/j.chemphyslip.2021.105113 -
Molecules (Basel, Switzerland) Mar 2021In this study, the general processability of cannabidiol (CBD) in colloidal lipid carriers was investigated. Due to its many pharmacological effects, the pharmaceutical...
In this study, the general processability of cannabidiol (CBD) in colloidal lipid carriers was investigated. Due to its many pharmacological effects, the pharmaceutical use of this poorly water-soluble drug is currently under intensive research and colloidal lipid emulsions are a well-established formulation option for such lipophilic substances. To obtain a better understanding of the formulability of CBD in lipid emulsions, different aspects of CBD loading and its interaction with the emulsion droplets were investigated. Very high drug loads (>40% related to lipid content) could be achieved in emulsions of medium chain triglycerides, rapeseed oil, soybean oil and trimyristin. The maximum CBD load depended on the type of lipid matrix. CBD loading increased the particle size and the density of the lipid matrix. The loading capacity of a trimyristin emulsion for CBD was superior to that of a suspension of solid lipid nanoparticles based on trimyristin (69% vs. 30% related to the lipid matrix). In addition to its localization within the lipid core of the emulsion droplets, cannabidiol was associated with the droplet interface to a remarkable extent. According to a stress test, CBD destabilized the emulsions, with phospholipid-stabilized emulsions being more stable than poloxamer-stabilized ones. Furthermore, it was possible to produce emulsions with pure CBD as the dispersed phase, since CBD demonstrated such a pronounced supercooling tendency that it did not recrystallize, even if cooled to -60 °C.
Topics: Cannabidiol; Drug Carriers; Drug Delivery Systems; Emulsifying Agents; Emulsions; Lipid Droplets; Nanoparticles; Particle Size; Phospholipids; Rapeseed Oil; Soybean Oil; Water
PubMed: 33800445
DOI: 10.3390/molecules26051469 -
Molecules (Basel, Switzerland) Sep 2019Various bioactive compounds (BCs) often possess poor stability and bioavailability, which makes it difficult for them to exert their potential health benefits. These... (Review)
Review
Various bioactive compounds (BCs) often possess poor stability and bioavailability, which makes it difficult for them to exert their potential health benefits. These limitations can be countered by the use of nano-delivery systems (NDSs), such as nanoparticles and nanoemulsions. NDSs can protect BCs against harsh environments during food processing and digestion, and thereby, could enhance the bioavailability of BCs. Although various NDSs have been successfully produced with both synthetic and natural materials, it is necessary to fulfill safety criteria in the delivery materials for food applications. Food-grade materials for the production of NDSs, such as milk proteins and carbohydrates, have received much attention due to their low toxicity, biodegradability, and biocompatibility. Among these, whey proteins-from whey, a byproduct of cheese manufacturing-have been considered as excellent delivery material because of their high nutritional value and various functional properties, such as binding capability to various compounds, gelation, emulsifying properties, and barrier effects. Since the functional and physicochemical properties of whey protein-based NDSs, including size and surface charge, can be key factors affecting the applications of NDSs in food, the objectives of this review are to discuss how manufacturing variables can modulate the functional and physicochemical properties of NDSs and bioavailability of encapsulated BCs to produce efficient NDSs for various BCs.
Topics: Biological Availability; Drug Delivery Systems; Emulsions; Food Handling; Gels; Humans; Milk Proteins; Nanoparticles; Particle Size; Whey Proteins
PubMed: 31500127
DOI: 10.3390/molecules24183254 -
Molecules (Basel, Switzerland) May 2022In the present study, chitosan-decorated multiple nanoemulsion (MNE) was formulated using a two-step emulsification process. The formulated multiple nanoemuslion was...
In the present study, chitosan-decorated multiple nanoemulsion (MNE) was formulated using a two-step emulsification process. The formulated multiple nanoemuslion was evaluated physiochemically for its size and zeta potential, surface morphology, creaming and cracking, viscosity and pH. A Franz diffusion cell apparatus was used to carry out in vitro drug-release and permeation studies. The formulated nanoemulsion showed uniform droplet size and zeta potential. The pH and viscosity of the formulated emulsion were in the range of and suitable for topical delivery. The drug contents of the simple nanoemulsion (SNE), the chitosan-decorated nanoemulsion (CNE) and the MNE were 71 ± 2%, 82 ± 2% and 90 ± 2%, respectively. The formulated MNE showed controlled release of itraconazole as compared with that of the SNE and CNE. This was attributed to the chitosan decoration as well as to formulating multiple emulsions. The significant permeation and skin drug retention profile of the MNE were attributed to using the surfactants tween 80 and span 20 and the co-surfactant PEG 400. ATR-FTIR analysis confirmed that the MNE mainly affects the lipids and proteins of the skin, particularly the , which results in significantly higher permeation and retention of the drug. It was concluded that the proposed MNE formulation delivers drug to the target site of the skin and can be therapeutically used for various cutaneous fungal infections.
Topics: Administration, Cutaneous; Chitosan; Emulsions; Skin; Skin Absorption; Surface-Active Agents
PubMed: 35630660
DOI: 10.3390/molecules27103183 -
Advanced Healthcare Materials Apr 2022Poly(lactide-co-glycolide) (PLGA) has been extensively used in making long-acting injectable formulations. The critical factors affecting the PLGA formulation properties...
Poly(lactide-co-glycolide) (PLGA) has been extensively used in making long-acting injectable formulations. The critical factors affecting the PLGA formulation properties have been adjusted to control the drug release kinetics and obtain desirable properties of PLGA-based drug delivery systems. The PLGA microparticle formation begins as soon as the drug/PLGA-dissolved in the organic solvent phase (oil phase) is exposed to the water phase. The initial skin (or shell) formation on the oil droplets occurs very quickly, sometimes in the matter of milliseconds, and studying the process has been difficult. The skin formation on the PLGA emulsion droplet surface that can affect the subsequent hardening steps is examined. PLGA droplets with different compositions are prepared. Using collimated light and a high-speed camera made it possible to detect the diffusion of acetonitrile from the oil phase into the water phase during the oil droplet formation. Although the skin formation is not visible on the surface of the oil phase droplet with the current setup, the droplet shapes, solid strand formation, and the difference in the spreading time suggest that the initial contact time between the oil and water phases in the range of a few seconds is critical to the properties of the skin.
Topics: Drug Liberation; Emulsions; Microspheres; Particle Size; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer
PubMed: 34601826
DOI: 10.1002/adhm.202101427 -
Scientific Reports Sep 2023Neuroblastoma, the most common type of pediatric extracranial solid tumor, causes 10% of childhood cancer deaths. Despite intensive multimodal treatment, the outcomes of...
Neuroblastoma, the most common type of pediatric extracranial solid tumor, causes 10% of childhood cancer deaths. Despite intensive multimodal treatment, the outcomes of high-risk neuroblastoma remain poor. We urgently need to develop new therapies with safe long-term toxicity profiles for rapid testing in clinical trials. Drug repurposing is a promising approach to meet these needs. Here, we investigated disulfiram, a safe and successful chronic alcoholism treatment with known anticancer and epigenetic effects. Disulfiram efficiently induced cell cycle arrest and decreased the viability of six human neuroblastoma cell lines at half-maximal inhibitory concentrations up to 20 times lower than its peak clinical plasma level in patients treated for chronic alcoholism. Disulfiram shifted neuroblastoma transcriptome, decreasing MYCN levels and activating neuronal differentiation. Consistently, disulfiram significantly reduced the protein level of lysine acetyltransferase 2A (KAT2A), drastically reducing acetylation of its target residues on histone H3. To investigate disulfiram's anticancer effects in an in vivo model of high-risk neuroblastoma, we developed a disulfiram-loaded emulsion to deliver the highly liposoluble drug. Treatment with the emulsion significantly delayed neuroblastoma progression in mice. These results identify KAT2A as a novel target of disulfiram, which directly impacts neuroblastoma epigenetics and is a promising candidate for repurposing to treat pediatric neuroblastoma.
Topics: Animals; Child; Humans; Mice; Alcohol Deterrents; Cell Line, Tumor; Disulfiram; Down-Regulation; Drug Repositioning; Emulsions; Histone Acetyltransferases; Neuroblastoma
PubMed: 37777587
DOI: 10.1038/s41598-023-43219-2