Alejandro Sosnik

Alejandro Sosnik
Technion - Israel Institute of Technology | technion · Faculty of Materials Science and Engineering

Ph.D., Hebrew U of Jerusalem

About

223
Publications
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Publications

Publications (223)
Article
Mucosal tissues represent a major interface between the body and the external environment and are covered by a highly hydrated mucins gel called mucus. Mucus lubricates, protects and modulate the moisture levels of the tissue and has been capitalized in transmucosal drug delivery. Pharmaceutical researchers often use freshly excised animal mucosal...
Article
Full-text available
Biomaterial-centered infections of orthopedic implants remain a significant burden in the healthcare system due to sedentary lifestyles and an aging population. One approach to combat infections and improve implant osteointegration is functionalizing the implant surface with anti-infective and osteoinductive agents. In this framework, Au nanopartic...
Chapter
Natural polymers, also known as biopolymers, are polymers produced and isolated from living organisms such as plants, animals and microorganisms. They are biodegradable, avoiding the contamination of the planet, and they often display good biocompatibility and low toxicity with limited adverse effects. One of the main advantages of using biopolymer...
Article
Full-text available
Sonodynamic therapy (SDT) is an anti‐cancer therapeutic strategy based on the generation of reactive oxygen species (ROS) upon local ultrasound (US) irradiation of sono‐responsive molecules or nanomaterials that accumulate in the tumor. In this work, the sonodynamic efficiency of sono‐responsive hybrid nanomaterials composed of amorphous titanium d...
Article
Gout is a common inflammatory arthritis caused by persistently elevated uric acid levels. With the improvement of people's living standards, the consumption of processed food and the widespread use of drugs that induce elevated uric acid, gout rates are increasing, seriously affecting the human quality of life, and becoming a burden to health syste...
Article
Macrophages are immune cells that can be activated into either pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Attempts to modulate macrophage phenotype using drugs have been limited by targeting issues and systemic toxicity. This study investigates the effect of drug-free self-assembled hydrolyzed galactomannan-poly(methyl methacrylate) (h...
Article
The gold standard drug for colorectal cancer treatment, 5-Fluorouracil (5-FU), induces pharmacological tolerance in long-term management. The transcriptional factor NFκB plays a key role in 5-FU resistance. The aim of this work is to study the capability of polyelectrolytes complex nanoparticles of dermatan sulfate (DS) and chitosan, loaded with th...
Article
Based on stimuli in the biological milieu, macrophages can undergo classical activation into the M1 pro-inflammatory (anti-cancer) phenotype or to the alternatively activated M2 anti-inflammatory one. Drug-free biomaterials have emerged as a new therapeutic strategy to modulate macrophage phenotype. Among them, polysaccharides polarize macrophages...
Article
Cannabidiol (CBD), a non-psychoactive constituent of Cannabis, has proven neuroprotective, anti-inflammatory and antioxidant properties though his therapeutic use, especially by the oral route, is still challenged by the poor aqueous solubility that results in low oral bioavailability. In this work, we investigate the encapsulation of CBD within na...
Preprint
Full-text available
With the approval of the FDA Modernization Act 2.0, the pharmaceutical industry is poised to expand its research components with a plethora of alternative models, including organ-on-microfluidic chips in pharma and biotechnology, resulting in a personalized approach. Microfluidics opens new possibilities for the study of cell biology, especially fo...
Preprint
Full-text available
Cannabidiol (CBD), a non-psychoactive constituent of Cannabis , has proven neuroprotective, anti-inflammatory and antioxidant properties though his therapeutic use, especially by the oral route, is still challenged by the poor aqueous solubility that results in low oral bioavailability. In this work, we investigate the encapsulation of CBD within n...
Preprint
Biodegradable metals emerged as promising temporary bone implants. The integration of additional features such as local drug delivery (LDD) can also support their osteointegration, promote bone regeneration, and prevent biomaterial-centered infections that are difficult to treat. LDD is achieved by drug-eluting coatings or porous implants where the...
Article
Nanonization of poorly water-soluble drugs has shown great potential in improving their oral bioavailability by increasing drug dissolution rate and adhesion to the gastrointestinal mucus. However, the fundamental features that govern the particle-mucus interactions have not been investigated in a systematic way before. In this work, we synthesize...
Article
Sialic acid is a fundamental component of the tumor microenvironment, modulates cell–cell and cell-extracellular matrix interactions and is associated with bad prognosis and clinical outcomes in different cancers. Capitalizing on the ability of boric acid to form cyclic esters with diols, in this work, we design self-assembled multi-micellar colloi...
Preprint
Nanonization of poorly water-soluble drugs has shown great potential in improving their oral bioavailability by enhancing the dissolution rate and saturation solubility. Moreover, due to particle size reduction and larger surface area, the number of contact points with the gastrointestinal mucus favors adhesion. Similar phenomena could be anticipat...
Article
Full-text available
Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system (CNS) and result in their damage and death. Neurodevelopmental disorders include intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder and stem from the disruption of essential neurodevelopmental proc...
Article
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In this work, levofloxacin (LVX), a third‐generation fluoroquinolone antibiotic, is encapsulated within amphiphilic polymeric nanoparticles of a chitosan‐g‐poly(methyl methacrylate) produced by self‐assembly and physically stabilized by ionotropic crosslinking with sodium tripolyphosphate. Non‐crosslinked nanoparticles display a size of 29 nm and a...
Article
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The SARS CoV-2 virus emerged at the end of 2019 and rapidly developed several mutated variants, specifically the Delta and Omicron, which demonstrate higher transmissibility and escalating infection cases worldwide. The dominant transmission pathway of this virus is via human-to-human contact and aerosols which once inhaled interact with the mucosa...
Article
Microgels absorb and retain high amounts of solvents, especially water. Because of their size, and association, the release kinetics of active molecules from microgels is easier to control than in hydrogels. Collagen I is one of the most extensively investigated biomaterials, although the key process parameters to produce microgels must be understo...
Preprint
Full-text available
The SARS CoV-2 virus emerged at the end of 2019 and rapidly developed several mutated variants, specifically the Delta and Omicron, which demonstrate higher infectivity and escalating infection cases worldwide. The dominant transmission pathway of this virus is via human-to-human contact and aerosols, but another possible route is through contact w...
Article
Full-text available
Ocular drug delivery is challenging due to the very short drug residence time and low permeability. In this work, we produce and characterize mucoadhesive mixed polymeric micelles (PMs) made of chitosan (CS) and poly(vinyl alcohol) backbones graft-hydrophobized with short poly(methyl methacrylate) blocks and use them to encapsulate cannabidiol (CBD...
Article
Sonodynamic therapy is a cost-effective, minimally invasive and localized anticancer therapy based on the in situ generation of reactive oxygen species by combining low-intensity ultrasound (US), oxygen, and a sonosensitizer and it minimizes systemic toxicity. In this work, we initially study the effect of poly(ethylene oxide)-poly(propylene oxide)...
Article
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein overexpressed by several cancers. Because SPARC shows high binding affinity to albumin, we reasoned that pediatric sarcoma xenografts expressing SPARC would show enhanced uptake and accumulation of nanoparticle albumin-bound (nab)-paclitaxel, a potent anticancer dr...
Preprint
Ocular drug delivery is one of the most challenging administration routes due to the very low drug bioavailability. In this work, we produce and characterize mucoadhesive mixed polymeric micelles (PMs) made of chitosan and poly(vinyl alcohol) backbones graft-hydrophobized with short poly(methyl methacrylate) blocks and use them to encapsulate canna...
Article
Macrophages are highly plastic phagocytic cells that can exist in distinct phenotypes and play key roles in physiological and pathological pathways. They can be classically activated to the pro-inflammatory M1 phenotype or alternatively activated to an M2 anti-inflammatory one by various stimuli in the biological milieu. Different biomaterials pola...
Chapter
Dynamic soft materials that have the ability to expand and contract, change stiffness, self-heal or dissolve in response to environmental changes, are of great interest in applications ranging from biosensing and drug delivery to soft robotics and tissue engineering. This book covers the state-of-the-art and current trends in the very active and ex...
Article
The antiretroviral (ARV) cocktail revolved the treatment of the human immunodeficiency virus (HIV) infection. Drug combinations have been also tested to treat other infectious diseases, including the recent coronavirus disease 2019 (COVID-19) outbreak. To simplify administration fixed-dose combinations have been introduced, however, oral anti-HIV t...
Article
Glioblastoma multiforme (GBM) remains a major cause of mortality because treatments are precluded by to the limited transport and penetration of chemotherapeutics across the blood–brain barrier. Pitavastatin (PTV) is a hydrophobic Food and Drug Administration (FDA)-approved anticholesterolemic agent with reported anti-GBM activity. In the present s...
Article
Oral administration is the most popular and patient-compliant route for drug delivery, though it raises great challenges due to the involvement of the gastro-intestine (GI) system and the drug bioavailability. Drug bioavailability is directly related to its ability to dissolve, transport and/or absorb through the physiological environment. A great...
Article
Full-text available
Extracellular vesicles (EVs) have recently gained growing interest for their diagnostic and therapeutic potential. Despite this, few protocols have been reported for the isolation of EVs with preserved biological function. Most EV purification methods include a precipitation step that results in aggregation of vesicles and most available techniques...
Article
Full-text available
Nanoprecipitation is one of the most versatile methods to produce pure drug nanoparticles (PDNPs) owing to the ability to optimize the properties of the product. Nevertheless, nanoprecipitation may result in broad particle size distribution, low physical stability, and batch-to-batch variability. Microfluidics has emerged as a powerful tool to prod...
Article
Extracellular vesicles (EVs) have emerged as a promising strategy to promote tissue regeneration. However, overcoming the low EV production yield remains a big challenge in translating EV-based therapies to the clinical practice. Current EV production relies heavily on 2D cell culture, which is not only less physiologically relevant to cells but al...
Article
Biodegradable metals in orthopedics are aimed to eliminate secondary surgical intervention for implant removal, and thus improve patient compliance, reduce operational costs and the risk of infections. In addition, biodegradable implants could be loaded with different drugs to prevent the growth of pathogens and the development of bone infections,...
Preprint
Full-text available
Extracellular vesicles (EVs) have recently gained growing interest for their diagnostic and therapeutic potential. Despite this, few protocols have been reported for the isolation of EVs with preserved biological function. Most EV purification methods include a precipitation step that results in aggregation of vesicles and most available techniques...
Article
Full-text available
Boron nitride quantum dots (BNQDs) have been proposed as probe for bioimaging owing to outstanding photoluminescence properties though its hydrophobic nature and strong aggregation tendency in aqueous media limit their application in the biomedical field. In this work, we synthesize BNQDs by utilizing a liquid exfoliation-solvothermal process under...
Article
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Nanoneuromedicine investigates nanotechnology to target the brain and treat neurological diseases. In this work, we biofabricated heterocellular spheroids comprising human brain microvascular endothelial cells, brain vascular pericytes and astrocytes combined with primary cortical neurons and microglia isolated from neonate rats. The structure and...
Article
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Aerogels are the lightest processed solid materials on Earth and with the largest empty volume fraction in their structure. Composition versatility, modularity, and feasibility of industrial scale manufacturing are behind the fast emergence of aerogels in the drug delivery field. Compared to other 3D materials, the high porosity (interconnected mes...
Article
Diffuse intrinsic pontine glioma (DIPG) is a chemo-resistant, incurable pediatric tumor of the central nervous system (CNS). The blood-brain barrier (BBB) remains intact in the course of the disease, preventing drugs from entering the brain and resulting in therapeutic failure. The topoisomerase I inhibitor SN-38 shows strong anticancer activity in...
Article
In this work, we investigated terpyridine (tpy)/Zn(II) complexation for the crosslinking of polymeric micelles of the branched poly(ethylene oxide)–poly(propylene oxide) block copolymer Tetronic® 1107 (T1107) in water and produce physically stable amphiphilic luminescent nanogels. Nanoparticles displayed a size of 235 ± 25 and 318 ± 57 nm before an...
Article
Full-text available
Intranasal (i.n.) administration became an alternative strategy to bypass the blood–brain barrier and improve drug bioavailability in the brain. The main goal of this work was to preliminarily study the biodistribution of mixed amphiphilic mucoadhesive nanoparticles made of chitosan-g-poly(methyl methacrylate) and poly(vinyl alcohol)-g-poly(methyl...
Article
Full-text available
Biological gels (bio-gels) are hydrated polymer networks that serve diverse biological functions, which often lead to intentional or unintentional exposure to particulate matter. In this work, we derive a microscopically motivated framework that enables the investigation of penetration mechanisms into bio-gels. We distinguish between two types of m...
Article
The blood-brain barrier (BBB) is a challenge for the treatment of diseases of the central nervous system (CNS) from the systemic circulation. The design of novel strategies to increase drug bioavailability into the CNS is called for. In this work, we synthesized amphiphilic polymeric nanoparticles by the self-assembly of graft copolymers of chitosa...
Preprint
The treatment of neurological disorders (NDs) is challenged by low dug permeability from the systemic circulation into the central nervous system (CNS) owing to the presence of the blood brain barrier (BBB). Neuronanomedicine investigates nanotechnology strategies to target the brain and improve the therapeutic outcome in NDs. 2D adherent cell BBB...
Article
This review provides an integrative overview of the complex interactions between nanomaterials and mucosae, and their implications to nanomedicine and nanotoxicology.
Article
Full-text available
This work investigates the potential of glycosylation to actively target nanodrug delivery systems to adult solid tumors overexpressing glucose transporters. The highly hydrophobic fluorescent compound curcumin (CUR) is nanoencapsulated within polymeric micelles of pristine and glucosylated poly(ethylene oxide)‐poly(propylene oxide) block copolymer...
Chapter
Overexpression of pumps of the Human adenosine triphosphate (ATP)-binding cassette (ABCs) plays a key role in cancer multidrug resistance (MDR) and chemotherapy failure. Since their discovery in the 1970s, ABCs attracted the attention as possible targets to overcome MDR. In this context, several generations of pharmacological ABC inhibitors have be...
Chapter
The oral route is the most patient-compliant and widely used due to characteristics such as self-administration, minimal invasiveness and ease of use. In addition, oral pharmaceutical products are more cost-effective. However, this route presents several challenges such as the harsh stomach environment with low pH, enzymatic activity and mechanical...
Article
Full-text available
Interferon alpha (IFNα) is a protein drug used to treat viral infections and cancer diseases. Due to its poor stability in the gastrointestinal tract, only parenteral administration ensures bioavailability, which is associated with severe side effects. We hypothesized that the nanoencapsulation of IFNα within nanoparticles of the mucoadhesive polys...
Article
This work describes a novel delivery system for targeting egg-derived anti-inflammatory tripeptide Ile-Arg-Trp (IRW) to endothelial cells. The nanomedicine is synthesized by a simple and reproducible ionotropic gelification method that results in the efficient loading of the positively charged IRW within the dermatan sulfate/ chitosan matrix, as de...
Article
Laccases are multi-copper oxidase enzymes having widespread applications in various biotechnological fields. However, low stability of free enzymes restricts their industrial use. Development of effective methods to preserve and even increase the enzymatic activity is critical to maximize their use, though this remains a challenge. In the present s...
Article
Full-text available
The nose‐to‐brain (N‐to‐B) transport mechanism of nanoparticles through the olfactory epithelium (OE) is not fully understood. Most research utilized nasal epithelial cell models completely deprived of olfactory cells. Aiming to shed light into key cellular pathways, in this work, for the first time, the interaction of polymeric nanoparticles in a...
Article
In this work, we designed, characterized and investigated the performance of hydrolyzed galactomannan (hGM)-based amphiphilic nanoparticles for selective intratumoral accumulation in pediatric patient-derived sarcomas. To create a self-assembly amphiphilic copolymer, the side chain of hGM was hydrophobized with poly(methyl methacrylate) (PMMA) by u...
Article
Effective and timeous delivery of therapeutic agents from the systemic circulation to the central nervous system (CNS) is often precluded by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). A new pathway of folate uptake mediated by folate receptor alpha (FRα, molecular weight of 28.29 kg mol-1) occurring in various...
Article
Full-text available
In this work, we aimed to improve the encapsulation efficiency of sepiapterin (SP), the natural precursor of the essential cofactor tetrahydrobiopterin (BH4) that displays mild water-solubility and a short biological half-life, within methoxy-poly(ethylene-glycol)-poly(epsilon-caprolactone)(mPEG-PCL) nanoparticles (NPs) by means of its complexation...
Poster
Full-text available
Sambucus nigra L. (Adoxaceae) is a species widely used in traditional medicine to treat several diseases (1). This study aims to scientifically evaluate the use of Sambucus nigra for cosmetological use.
Article
Hypothesis Poly(vinyl alcohol)-g-poly(methyl methacrylate) (PVA-g-PMMA) amphiphilic copolymers self-assemble to form multi-micellar colloidal systems. Experiments A PVA-g-PMMA copolymer containing 16–17% w/w of PMMA was synthesized by the free radical graft polymerization of methyl methacrylate on a PVA backbone by utilizing cerium(IV) ammonium ni...
Article
Intranasal administration of nano-drug delivery systems emerged as an appealing strategy to surpass the blood-brain barrier and thus, increase drug bioavailability in the central nervous system. However, a systematic study of the effect of structural properties of the nanoparticles on the nose-to-brain transport is missing. In this work, we synthes...
Article
Full-text available
A novel combination of block copolymer (BCP) nano spray‐drying (NSD), solvent annealing, and selective metal oxide growth is utilized to create functional polymer nanoparticles, polymer‐metal‐oxide hybrid nanoparticles, and templated metal oxide nanoparticles with tunable composition, internal morphology, and porosity. NSD of BCPs from chloroform a...
Article
Hyaluronic acid (HA) is commonly used through intra-articular administration for viscosupplementation in osteoarthritis and other disorders. HA is generally supplied as an injection commonly reported as painful, with strong limitations after treatment. In this study, an alternative delivery system was constructed based on HA hydrogel and poly(lacti...
Article
Full-text available
The most important prerequisites for wound coverage matrices are biocompatibility, adequate porosity, degradability and exudate uptake capacity. A moderate hydrophilicity and exudate uptake capacity can often favour cell adhesion and wound healing potential, however, most of the synthetic polymers like polycaprolactone (PCL) are hydrophobic. Hydrog...
Article
In this work, we synthesized and characterized the self-assembly behavior of a chitosan-poly(methyl methacrylate) graft copolymer and the properties of the formed nanoparticles by static and dynamic light scattering, small-angle neutron scattering, and transmission electron microscopy. Overall, our results indicate that the hydrophobization of the...
Article
Full-text available
This work describes for the first time the synthesis of hybrid drug‐loaded TiO2/polymer amphiphilic nanoparticles of finely controlled size utilizing a simple and reproducible sol–gel process that comprises the formation of a titanium(IV)/acetone oxo‐organo complex followed by its blending with an amphiphilic poly(ethylene oxide)‐b‐poly(propylene o...
Article
In recent years, nanotechnology has offered attractive opportunities to overcome the (bio)pharmaceutical drawbacks of most drugs such as low aqueous solubility and bioavailability. Among the numerous methodologies that have been applied to improve drug performance, a special emphasis has been made on those that increase the dissolution rate and the...
Article
Delivery of chemotherapy in the surgical bed has shown preclinical activity to control cancer progression upon subtotal resection of pediatric solid tumors, but whether this new treatment is safe for tumor‐adjacent healthy tissues remains unknown. Here, Wistar rats are used to study the anatomic and functional impact of electrospun nanofiber matric...
Article
In this work, we investigated for the first time the effect of the gradual increase of the glycosylation extent on self-assembly of a highly hydrophilic four-arm poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) block copolymer, Tetronic® 1107. After the initial characterization that confirmed the chemical modification, the effect of the glycosy...
Article
Despite the wide range of diseases affecting the eye, ocular bioavailability remains a challenge in ophthalmic drug delivery. Nowadays an extensive variety of polymers are being explored to develop colloidal drug carriers which show better performance than the more popular solutions. For instance, regardless of the type of polymer used, these syste...
Article
Statement of significance: Protease inhibitors (PIs) are gold-standard drugs in many ARV cocktails. Darunavir (DRV) is the latest approved PI and it is included in the 20th WHO Model List of Essential Medicines. PIs poorly-water soluble at intestinal pH and more soluble under gastric conditions. Drug nanonization represents one of the most common...
Article
Full-text available
Engineering of drug nanocarriers combining fine-tuned mucoadhesive/mucopenetrating properties is currently being investigated to ensure more efficient mucosal drug delivery. Aiming to improve the transmucosal delivery of hydrophobic drugs, we designed a novel nanogel produced by the self-assembly of amphiphilic chitosan graft copolymers ionotropica...