Search

There has been an increase in interest in the application of ω-3 PUFAs, especially EPA and DHA, in the development of various food products owing to their myriad health benefits. However, most fish oils do not contain more than 30% combined levels of EPA and DHA. In this study, through the urea complexation procedure, the production of EPA and DHA concentrate in their free fatty acids (FFAs) form was achieved from an enzymatic oil extracted from common kilka (Clupeonella cultriventris caspia). To gain the maximum value of EPA and DHA, the response surface methodology (RSM), which is an effective tool to categorize the level of independent variables onto the responses of an experimental process, was also used. Different variables including the urea–fatty acids (FAs) ratio (in the range of 2–6, w/w), the temperature of crystallization (in the range of −24–8 °C), and the time of crystallization (in the range of 8–40 h) were investigated by response surface methodology (RSM) for maximizing the EPA and DHA contents. Following the model validation, the levels of the variables at which the maximum desirability function (0.907 score) was obtained for response variables were 5:1 (urea–FAs ratio), −9 °C (the temperature of crystallization), and 24 h (the time of crystallization). Under these optimal conditions, increases of 2.2 and 4.4 times in the EPA and DHA concentrations were observed, respectively, and an increase in the concentrations of EPA and DHA from 5.39 and 13.32% in the crude oil to 12.07 and 58.36% in the ω-3 PUFA concentrates were observed, respectively. These findings indicate that the urea complexation process is efficient at optimizated conditions.

Implant-associated infections (IAIs) represent a major health burden due to the complex structural features of biofilms and their inherent tolerance to antimicrobial agents and the immune system. Thus, the viable options to eradicate biofilms embedded on medical implants are surgical operations and long-term and repeated antibiotic courses. Recent years have witnessed a growing interest in the development of robust and reliable strategies for prevention and treatment of IAIs. In particular, it seems promising to develop materials with anti-biofouling and antibacterial properties for combating IAIs on implants. In this contribution, we exclusively focus on recent advances in the development of modified and functionalized implant surfaces for inhibiting bacterial attachment and eventually biofilm formation on orthopedic implants. Further, we highlight recent progress in the development of antibacterial coatings (including self-assembled nanocoatings) for preventing biofilm formation on orthopedic implants. Among the recently introduced approaches for development of efficient and durable antibacterial coatings, we focus on the use of safe and biocompatible materials with excellent antibacterial activities for local delivery of combinatorial antimicrobial agents for preventing and treating IAIs and overcoming antimicrobial resistance.

The use of lipid nanocarriers for drug delivery applications is an active research area, and a great interest has particularly been shown in the past two decades. Among different lipid nanocarriers, ISAsomes (Internally self-assembled somes or particles), including cubosomes and hexosomes, and solid lipid nanoparticles (SLNs) have unique structural features, making them attractive as nanocarriers for drug delivery. In this contribution, we focus exclusively on recent advances in formation and characterization of ISAsomes, mainly cubosomes and hexosomes, and their use as versatile nanocarriers for different drug delivery applications. Additionally, the advantages of SLNs and their application in oral and pulmonary drug delivery are discussed with focus on the biological fates of these lipid nanocarriers in vivo. Despite the demonstrated advantages in in vitro and in vivo evaluations including preclinical studies, further investigations on improved understanding of the interactions of these nanoparticles with biological fluids and tissues of the target sites is necessary for efficient designing of drug nanocarriers and exploring potential clinical applications.

With the ability to cross biological barriers, encapsulate and efficiently deliver drugs and nucleic acid therapeutics, and protect the loaded cargos from degradation, different soft polymer and lipid nanoparticles (including liposomes, cubosomes, and hexosomes) have received considerable interest in the last three decades as versatile platforms for drug delivery applications and for the design of vaccines. Hard nanocrystals (including gold nanoparticles and quantum dots) are also attractive for use in various biomedical applications. Here, microfluidics provides unique opportunities for the continuous synthesis of these hard and soft nanomaterials with controllable shapes and sizes, and their in situ characterization through manipulation of the flow conditions and coupling to synchrotron small-angle X-ray (SAXS), wide-angle scattering (WAXS), or neutron (SANS) scattering techniques, respectively. Two-dimensional (2D) and three-dimensional (3D) microfluidic devices are attractive not only for the continuous production of monodispersed nanomaterials, but also for improving our understanding of the involved nucleation and growth mechanisms during the formation of hard nanocrystals under confined geometry conditions. They allow further gaining insight into the involved dynamic structural transitions, mechanisms, and kinetics during the generation of self-assembled nanostructures (including drug nanocarriers) at different reaction times (ranging from fractions of seconds to minutes). This review provides an overview of recently developed 2D and 3D microfluidic platforms for the continuous production of nanomaterials, and their simultaneous use in in situ characterization investigations through coupling to nanostructural characterization techniques (e.g., SAXS, WAXS, and SANS).

Krill oil represents an important alternative natural source of omega-3 (ω-3) polyunsaturated fatty acids (PUFAs). Considering the beneficial health effects of these essential fatty acids, particularly in various disorders including cancer, cardiovascular, and inflammation diseases, it is of paramount importance to gain insight into the digestibility of krill oil. In this work, we study the fate of krill oil-in-water emulsion, stabilized by sodium caseinate, during lipolysis by coupling time-resolved synchrotron small-angle X-ray scattering (SAXS) to flow-through lipolysis model. For gaining further insight into the effect of ω-3 PUFA-containing oil type on the dynamic structural features occurring during lipolysis, two additional astaxanthin oil-in-water emulsions, stabilized using either sodium caseinate or citrem, were subjected to lipolysis under identical experimental conditions. In addition to the difference in lipid composition in both oils, ω-3 PUFAs in astaxanthin oil, similar to fish oil, exist in the form of triacylglycerols; whereas most of those in krill oil are bound to phospholipids. SAXS showed the formation of highly ordered nanostructures on exposure of these food emulsions to the lipolysis medium: the detection of a biphasic feature of coexisting inverse hexagonal (H2) and lamellar (Lα) liquid crystalline phases in the digested krill oil droplets' interiors, as compared to a neat Lα phase in the digested astaxanthin oil droplets. We discuss the dynamic phase behavior and describe the suggested important role of these phases in facilitating the delivery of nutrients throughout the body. In addition, the potential implication in the development of food and drug nanocarriers is briefly described.

Lung cancer (LC) is the leading cause of cancer-related deaths, responsible for approximately 18.4% of all cancer mortalities in both sexes combined. The use of systemic therapeutics remains one of the primary treatments for LC. However, the therapeutic efficacy of these agents is limited due to their associated severe adverse effects, systemic toxicity and poor selectivity. In contrast, pulmonary delivery of anticancer drugs can provide many advantages over conventional routes. The inhalation route allows the direct delivery of chemotherapeutic agents to the target LC cells with high local concertation that may enhance the antitumor activity and lead to lower dosing and fewer systemic toxicities. Nevertheless, this route faces by many physiological barriers and technological challenges that may significantly affect the lung deposition, retention, and efficacy of anticancer drugs. The use of lipid-based nanocarriers could potentially overcome these problems owing to their unique characteristics, such as the ability to entrap drugs with various physicochemical properties, and their enhanced permeability and retention (EPR) effect for passive targeting. Besides, they can be functionalized with different targeting moieties for active targeting. This article highlights the physiological, physicochemical, and technological considerations for efficient inhalable anticancer delivery using lipid-based nanocarriers and their cutting-edge role in LC treatment.

Lamellar and non-lamellar liquid crystalline nanodispersions, including liposomes, cubosomes, and hexosomes are attractive platforms for drug delivery, bio-imaging, and related pharmaceutical applications. As compared to liposomes, there is a modest number of reports on the continuous production of cubosomes and hexosomes. Using a binary lipid mixture of citrem and soy phosphatidylcholine (SPC), we describe the continuous production of nanocarriers for delivering thymoquinone (TQ, a substance with various therapeutic potentials) by employing a commercial microfluidic hydrodynamic flow-focusing chip. In this study, nanoparticle tracking analysis (NTA) and synchrotron small-angle X-ray scattering (SAXS) were employed to characterize TQ-free and TQ-loaded citrem/SPC nanodispersions. Microfluidic synthesis led to formation of TQ-free and TQ-loaded nanoparticles with mean sizes around 115 and 124 nm, and NTA findings indicated comparable nanoparticle size distributions in these nanodispersions. Despite the attractiveness of the microfluidic chip for continuous production of citrem/SPC nano-self-assemblies, it was not efficient as comparable mean nanoparticle sizes were obtained on employing a batch (discontinuous) method based on low-energy emulsification method. SAXS results indicated the formation of a biphasic feature of swollen lamellar (Lα) phase in coexistence with an inverse bicontinuous cubic Pn3m phase in all continuously produced TQ-free and TQ-loaded nanodispersions. Further, a set of SAXS experiments were conducted on samples prepared using the batch method for gaining further insight into the effects of ethanol and TQ concentration on the structural features of citrem/SPC nano-self-assemblies. We discuss these effects and comment on the need to introduce efficient microfluidic platforms for producing nanocarriers for delivering TQ and other therapeutic agents.

Cryo-transmission electron microscopy (Cryo-TEM), and its technological variations thereof, have become a powerful tool for detailed morphological characterization and 3D tomography of soft lipid and polymeric nanoparticles as well as biological materials such as viruses and DNA without chemical fixation. Here, we review and discuss recent advances in Cryo-TEM analysis of lipid-based drug nanocarriers with particular emphasis on morphological and internal nanostructure characterization of lyotropic liquid crystalline nanoparticles such as cubosomes and hexosomes.