Department of Chemical and Biological Engineering

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Work by the faculty and students of the Department of Chemical Engineering

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    Finger-operated pumping platform for microfluidic preparation of nanoparticles
    (Springer, 2024) Azmeer, Ahmed; Kanan, Ibraheem; Husseini, Ghaleb; Abdelgawad, Mohammad
    Microfluidic preparation of nanoparticles (NPs) offers many advantages over traditional bench-top preparation techniques, including better control over particle size and higher uniformity. Although many studies have reported the use of low-cost microfluidic chips for nanoparticle synthesis, the technology is still expensive due to the high cost of the pumps needed to generate the required flows inside microchannels. Here, we present a low-cost finger-operated constant-pressure pumping platform capable of generating pressures as high as 120 kPa using finger-operated pumping caps that can be attached to any pop bottle. The platform costs around $208 and enables the generation of flow rate ratios (FRR) of up to 47:1 for the continuous flow synthesis of NPs. The pump has a resolution of 500 Pa per stroke and exhibits stable pressures for up to a few hours. To show the functionality of the proposed pump, we used it to prepare pegylated liposomes and poly lacticco-glycolic acid (PLGA) nanoparticles with sizes ranging from 47 nm to 250 nm with an average polydispersity of 20% using commercially available micromixer chips and in-house made hydrodynamic flow focusing devices. We believe this platform will render microfluidic preparation of NPs accessible to any laboratory with minimal capabilities.
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    Production of Targeted Estrone Liposomes Using a Herringbone Micromixer
    (IEEE, 2024) Agam, Mohamed Abdalla; Paul, Vinod; Abdelgawad, Mohammad; Husseini, Ghaleb
    Liposomes are spherical vesicles formed from bilayer lipid membranes that are extensively used in targeted drug delivery as nanocarriers to deliver therapeutic reagents to specific tissues and organs in the body. Recently, we have reported using estrone as an endogenous ligand on doxorubicin-encapsulating liposomes to target estrogen receptor (ER)-positive breast cancer cells. Estrone liposomes were synthesized using the thin-film hydration method, which is a long, arduous, and multistep process. Here, we report using a herringbone micromixer to synthesize estrone liposomes in a simple and rapid manner. A solvent stream containing the lipids was mixed with a stream of phosphate buffer saline (PBS) inside a microchannel integrated with herringbone-shaped ridges that enhanced the mixing of the two streams. The small scale involved enabled rapid solvent exchange and initiated the self-assembly of the lipids to form the required liposomes. The effect of different parameters on liposome size, such as the ratio between the flow rate of the solvent and the buffer solutions (FRR), total flow rate, lipid concentrations, and solvent type, were investigated. Using this commercially available chip, we obtained liposomes with a radius of 66.1 ± 11.2 nm (mean ± standard deviation) and a polydispersity of 22% in less than 15 minutes compared to a total of ∼ 11 hours using conventional techniques. Calcein was encapsulated inside the prepared liposomes as a model drug and was released by applying ultrasound at different powers. The size of the prepared liposomes was stable over a period of one month. Overall, using microfluidics to synthesize estrone liposomes simplified the procedure considerably and improved the reproducibility of the resulting liposomes.
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    Microwave-Responsive Metal-Organic Frameworks (MOFs) for Enhanced In Vitro Controlled Release of Doxorubicin
    (MDPI, 2024) Fatima, Syeda Fiza; Sabouni, Rana; Husseini, Ghaleb; Paul, Vinod; Gomaa, Hassan
    Metal-organic frameworks (MOFs) are excellent candidates for a range of applications because of their numerous advantages, such as high surface area, porosity, and thermal and chemical stability. In this study, microwave (MW) irradiation is used as a novel stimulus in vitro controlled release of Doxorubicin (DOX) from two MOFs, namely Fe-BTC and MIL-53(Al), to enhance drug delivery in cancer therapy. DOX was encapsulated into Fe-BTC and MIL-53(Al) with drug-loading efficiencies of up to 67% for Fe-BTC and 40% for MIL-53(Al). Several characterization tests, including XRD, FTIR, TGA, BET, FE-SEM, and EDX, confirmed both MOF samples’ drug-loading and -release mechanisms. Fe-BTC exhibited a substantial improvement in drug-release efficiency (54%) when exposed to microwave irradiation at pH 7.4 for 50 min, whereas 11% was achieved without the external modality. A similar result was observed at pH 5.3; however, in both cases, the release efficiencies were substantially higher with microwave exposure (40%) than without (6%). In contrast, MIL-53(Al) exhibited greater sensitivity to pH, displaying a higher release rate (66%) after 38 min at pH 5.3 compared to 55% after 50 min at pH 7.4 when subjected to microwave irradiation. These results highlight the potential of both MOFs as highly heat-responsive to thermal stimuli. The results of the MTT assay demonstrated the cell viability across different concentrations of the MOFs after two days of incubation. This suggests that MOFs hold promise as potential candidates for tumor targeting. Additionally, the fact that the cells maintained their viability at different durations of microwave exposure confirms that the latter is a safe modality for triggering drug release from MOFs.
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    Recent Advancements in Bone Tissue Engineering: Integrating Smart Scaffold Technologies and Bio-Responsive Systems for Enhanced Regeneration
    (MDPI, 2024) Percival, Kelly M.; Paul, Vinod; Husseini, Ghaleb
    In exploring the challenges of bone repair and regeneration, this review evaluates the potential of bone tissue engineering (BTE) as a viable alternative to traditional methods, such as autografts and allografts. Key developments in biomaterials and scaffold fabrication techniques, such as additive manufacturing and cell and bioactive molecule-laden scaffolds, are discussed, along with the integration of bio-responsive scaffolds, which can respond to physical and chemical stimuli. These advancements collectively aim to mimic the natural microenvironment of bone, thereby enhancing osteogenesis and facilitating the formation of new tissue. Through a comprehensive combination of in vitro and in vivo studies, we scrutinize the biocompatibility, osteoinductivity, and osteoconductivity of these engineered scaffolds, as well as their interactions with critical cellular players in bone healing processes. Findings from scaffold fabrication techniques and bio-responsive scaffolds indicate that incorporating nanostructured materials and bioactive compounds is particularly effective in promoting the recruitment and differentiation of osteoprogenitor cells. The therapeutic potential of these advanced biomaterials in clinical settings is widely recognized and the paper advocates continued research into multi-responsive scaffold systems.
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    Modeling of brain tumors using in vitro, in vivo, and microfluidic models: A review of the current developments
    (Elsevier, 2024) Raju, Richu; AlSawaftah, Nour Majdi; Husseini, Ghaleb
    Brain cancers are some of the most complex diseases to treat, despite the numerous advances science has made in cancer chemotherapy and research. One of the key obstacles to identifying potential cures for this disease is the difficulty in emulating the complexity of the brain and the surrounding microenvironment to understand potential therapeutic approaches. This paper discusses some of the most important in vitro, in vivo, and microfluidic brain tumor models that aim to address these challenges.
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    Enhancing Curcumin’s therapeutic potential in cancer treatment through ultrasound mediated liposomal delivery
    (Nature, 2024) Radha, Remya; Paul, Vinod; Anjum, Shabana; Bouakaz, Ayache; Pitt, William; Husseini, Ghaleb
    Improving the efficacy of chemotherapy remains a key challenge in cancer treatment, considering the low bioavailability, high cytotoxicity, and undesirable side effects of some clinical drugs. Targeted delivery and sustained release of therapeutic drugs to cancer cells can reduce the whole-body cytotoxicity of the agent and deliver a safe localized treatment to the patient. There is growing interest in herbal drugs, such as curcumin, which is highly noted as a promising anti-tumor drug, considering its wide range of bioactivities and therapeutic properties against various tumors. Conversely, the clinical efficacy of curcumin is limited because of poor oral bioavailability, low water solubility, instability in gastrointestinal fluids, and unsuitable pH stability. Drug-delivery colloid vehicles like liposomes and nanoparticles combined with microbubbles and ultrasound-mediated sustained release are currently being explored as effective delivery modes in such cases. This study aimed to synthesize and study the properties of curcumin liposomes (CLs) and optimize the high-frequency ultrasound release and uptake by a human breast cancer cell line (HCC 1954) through in vitro studies of culture viability and cytotoxicity. CLs were effectively prepared with particles sized at 81 ± 2 nm, demonstrating stability and controlled release of curcumin under ultrasound exposure. In vitro studies using HCC1954 cells, the combination of CLs, ultrasound, and Definity microbubbles significantly improved curcumin’s anti-tumor effects, particularly under specific conditions: 15 s of continuous ultrasound at 0.12 W/cm² power density with 0.6 × 10⁷ microbubbles/mL. Furthermore, the study delved into curcumin liposomes’ cytotoxic effects using an Annexin V/PI-based apoptosis assay. The treatment with CLs, particularly in conjunction with ultrasound and microbubbles, amplified cell apoptosis, mainly in the late apoptosis stage, which was attributed to heightened cellular uptake within cancer cells.
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    Hybrid liposome/metal–organic framework as a promising dual-responsive nanocarriers for anticancer drug delivery
    (Elsevier, 2022) Karami, Abdollah; Ahmed, Ahmed H.S; Sabouni, Rana; Husseini, Ghaleb; Al Sharabati, Miral Osama Yacoub; AlSawaftah, Nour Majdi; Paul, Vinod
    In this work, liposome-coated iron (III) benzene-1,3,5-tricarboxylate (Fe-BTC) metal–organic framework is examined as a promising pH/Ultrasound dual-responsive nanocarriers for doxorubicin (DOX) delivery. The successful coating of the MOF particles (Lip-Fe-BTC) with the phospholipid bilayer (PBL) was established by direct fusion into the synthesized liposomes. The liposome coating was verified using several techniques, including dynamic light scattering (DLS) and transmission electron microscopy (TEM). The DLS measurements showed an increase in the average particle diameter of liposomes from 150 nm to 163.1 nm for Lip-Fe-BTC particles. The Fe-BTC particles had the highest average particle diameter (287.3 nm). These results demonstrated that the PBL reduced the aggregation of the particles and improved their dispersity in the release medium. The TGA results demonstrated the MOF’s excellent thermal stability. Furthermore, the nanocarrier’s loading efficiency and capacity were determined to be ~90% and ~13.5 wt%, respectively. The in-vitro DOX release experiments demonstrated that the DOX-loaded Fe-BTC and liposome-coated Fe-BTC particles showed good pH and US dual-responsive capability, making them promising nanocarriers for drug delivery. The application of US enhanced DOX release from both Fe-BTC and liposome-coated Fe-BTC. In the case of Fe-BTC-DOX particles, the application of US enhanced the DOX release to around 38% and 67%, at pH levels of 7.4 and 5.3, respectively. Similarly, DOX release from the Lip-Fe-BTC-DOX particles reached ~35% and ~53%, at pH levels of 7.4 and 5.3, respectively. The MTT assay showed the biocompatibility and low cytotoxicity of these nanocarriers below 100 µg/ml.
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    pH and ultrasound dual-responsive drug delivery system based on PEG–folate-functionalized Iron-based metal–organic framework for targeted doxorubicin delivery
    (Elsevier, 2021) Ahmed, Ahmed H.S; Karami, Abdollah; Sabouni, Rana; Husseini, Ghaleb; Paul, Vinod
    In recent years, the use of metal–organic frameworks (MOFs) as drug nanocarriers has gained attention because of their extraordinary physical and chemical properties. In this work, dual-responsive iron-based MOFs were synthesized via the microwave-assisted method using FeCl₃.6 (H₂O) as the metal cluster and 2-aminoterephthalic acid (NH₂-BDC) as the organic linker (namely NH₂-Fe-BDC) and loaded with the anti-cancer drug doxorubicin (DOX). The DOX-loaded MOFs were further functionalized with polyethylene glycol-folate (PEG–FA), yielding PEG–FA-NH₂-Fe-BDC. The folate moiety is used to specifically target several cancers overexpressing the folate receptor (FR). These nanoparticles were characterized using Fourier-Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Thermogravimetric Analysis (TGA), and Dynamic Light Scattering (DLS). The FTIR confirmed the PEG–FA conjugation to the MOFs, while the XRD patterns confirmed the crystallinity of the nanoparticles. TGA results demonstrated the thermal stability of the MOFs. Moreover, the DLS analysis showed that regular MOFs had a particle diameter of 577 nm, while the PEG–FA-functionalized MOF had a particle diameter of 461 nm, which demonstrates the improved colloidal stability of the functionalized MOF. The DOX encapsulation efficiency was determined to be approximately 97%, while the encapsulation capacity was around 14.5 wt%. Furthermore, the in-vitro release profiles were studied under different pH values (5.3 and 7.4) with and without low-frequency ultrasound (LFUS, at 40 kHz). The results confirmed the sonosensitivity of the nanovehicles, with US-triggered release efficiency reaching up to 90% after 280 min (at a pH of 5.3). The MTT study revealed that these nanocarriers are non-toxic at lower concentrations. Their toxicity increases at higher concentrations. Furthermore, the cellular uptake was investigated via flow cytometry, and the results showed that the conjugation of the PEG-FA moiety to the MOF’s surface significantly enhanced uptake by cancer cells. Accordingly, this study showed the pH/US dual-responsive capability of NH₂-Fe-BDC and PEG–FA-NH₂-Fe-BDC.
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    Liposomes as a Promising Ultrasound-Triggered Drug Delivery System in Cancer Treatment
    (Bentham Science, 2017) Salkho, Najla; Turki, Renad; O, Guessoum; Martins, Ana M.; Vitor, Rute F.; Husseini, Ghaleb
    The initial uses of ultrasound waves in the medical field were limited to the thermal ablation of solid tumors and as a diagnostic tool. Recent advances at the preclinical stage have allowed the use of ultrasound as a powerful tool to improve drug delivery when the agent is administered encapsulated inside a nanoparticle. This spatial and temporal control of drug release, using a non-invasive modality, is a promising approach to decrease the side effects of conventional chemotherapy in cancer treatments, as it reduces the interaction of the anti-neoplastic agent with healthy tissues. In this review, we explain the physics of ultrasound, introduce and discuss several examples on the use of nanoparticles as drug carriers, with a focus on liposomes. Examples of in vitro and in vivo studies are presented and discussed.
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    Systems and Methods for Targeted Breast Cancer Therapies
    (2024-01-09) Husseini, Ghaleb; Al-Sayah, Mohammad; Ahmed, Amal Elsadig Elamir
    Systems and methods for producing liposomes, including control liposomes and immunoliposomes targeting breast cancer are provided. Systems and methods for treating breast cancer, using targeted immunoliposomes produced according to various methods are also disclosed herein. For example, trastuzumab-conjugated immunoliposomes may be used to deliver chemotherapeutic agents to breast cancer tissues for the treatment of breast cancer. Systems and methods for actuating liposomes using ultrasound are also disclosed, such as systems and methods for actuating trastuzumab-conjugated liposomes accumulated in breast cancer tissues for the treatment of breast cancer.
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    Systems and Methods for Targeted Breast Cancer Therapies
    (2020-12-15) Husseini, Ghaleb; Al-Sayah, Mohammad; Ahmed, Amal Elsadig Elamir
    Systems and methods for producing liposomes , including control liposomes and immunoliposomes targeting breast cancer are provided . Systems and methods for treating breast cancer , using targeted immunoliposomes produced according to various methods are also disclosed herein . For example, trastuzumab - conjugated immunoliposomes may be used to deliver chemotherapeutic agents to breast cancer tissues for the treatment of breast cancer . Systems and methods for actuating liposomes using ultrasound are also disclosed , such as systems and methods for actuating trastuzumab - conjugated liposomes accumulated in breast cancer tissues for the treatment of breast cancer.
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    Technique for Drug and Gene Delivery to the Cell Cytosol
    (2015-04-07) Pitt, William G.; Husseini, Ghaleb
    Provided herein is a composition, a method, and a system for delivering a functional molecule to the cytosol of a cell, comprising a liposome configured to be taken into a cell, including by a process selected from the group consisting of endocytosis, pinocytosis or phagocytosis, the liposome comprising a phase transforming liquid with vapor pressure capable of forming a gas at low pressure, said liquid being associated with the liposome, and the liposome further com prising at least one functional molecule selected from the group consisting of a therapeutic molecule, a detectable label, and a targeting molecule.
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    State-of-All-the-Art and Prospective Hydrogel-Based Transdermal Drug Delivery Systems
    (MDPI, 2024-03-30) Alex, Meera; AlSawaftah, Nour Majdi; Husseini, Ghaleb
    Over the past few decades, notable advancements have been made in the field of transdermal drug delivery systems (TDDSs), presenting a promising alternative to conventional oral drug administration. This comprehensive review aims to enhance understanding of this method by examining various transdermal techniques, the skin’s role as a barrier to TDDS, factors affecting skin diffusion, and current challenges in TDDSs. The primary focus of this analysis centers on TDDSs utilizing hydrogels. A thorough exploration of hydrogel fundamentals, encompassing structure, properties, and synthesis, is provided to underscore the importance of hydrogels as carriers in transdermal drug delivery. The concluding section delves into strategies for hydrogel-based drug delivery, addressing challenges and exploring future directions.
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    Nanoparticle-based materials in anticancer drug delivery: Current and future prospects
    (Elsevier, 2023) Ajith, Saniha Aysha; Almomani, Fares; Elhissi, Abdelbary; Husseini, Ghaleb
    The past decade has witnessed a breakthrough in novel strategies to treat cancer. One of the most common cancer treatment modalities is chemotherapy which involves administering anti-cancer drugs to the body. However, these drugs can lead to undesirable side effects on healthy cells. To overcome this challenge and improve cancer cell targeting, many novel nanocarriers have been developed to deliver drugs directly to the cancerous cells and minimize effects on the healthy tissues. The majority of the research studies conclude that using drugs encapsulated in nanocarriers is a much safer and more effective alternative than delivering the drug alone in its free form. This review provides a summary of the types of nanocarriers mainly studied for cancer drug delivery, namely: liposomes, polymeric micelles, dendrimers, magnetic nanoparticles, mesoporous nanoparticles, gold nanoparticles, carbon nanotubes and quantum dots. In this review, the synthesis, applications, advantages, disadvantages, and previous studies of these nanomaterials are discussed in detail. Furthermore, the future opportunities and possible challenges of translating these materials into clinical applications are also reported.
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    Encapsulation and release of calcein from herceptin-conjugated eLiposomes
    (Elsevier, 2024-03) Zafar, Mah Noor; Pitt, William G.; Husseini, Ghaleb
    Achieving an optimal therapeutic level is crucial in effectively eradicating cancer cells during treatment. However, conventional chemotherapy-associated systemic administration of anticancer agents leads to many side effects. To achieve the desired control over the target site, active targeting of HER2-positive breast cancer cells can be achieved by conjugating liposomal vesicles with Human Epidermal growth factor Receptor 2 (HER2) and inducing release of the encapsulated drug using ultrasound. To further enhance the delivery efficiency, nanoemulsion droplets exhibiting responsiveness to low-frequency ultrasound are encapsulated within these lipid vesicles. In this study, we prepared four different liposomal formulations, namely pegylated liposomes, emulsion liposomes (eLiposomes), HER-conjugated liposomes, and HER-conjugated eLiposomes, each loaded with calcein and subjected to a thorough characterization process. Their sizes, phospholipid concentration, and amount of antibody conjugation were compared and analyzed. Cryogenic transmission electron microscopy was used to confirm the encapsulation of nanoemulsion droplets within the liposomes. The drug-releasing performance of Herceptinconjugated eLiposomes was found to surpass that of other liposomal formulations with a notably higher calcein release and established it as a highly effective nanocarrier. The study showcases the efficacy of calcein-loaded and Herceptin-conjugated eLiposomes, which demonstrate rapid and efficient drug release among other liposomal formulations when subjected to ultrasound. This discovery paves the way for a more targeted, efficient, and humane approach to cancer therapy.
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    Scaffold‑based 3D cell culture models in cancer research
    (Springer Nature, 2024) Abuwatfa, Waad Hussein; Pitt, William G.; Husseini, Ghaleb
    Three-dimensional (3D) cell cultures have emerged as valuable tools in cancer research, offering significant advantages over traditional two-dimensional (2D) cell culture systems. In 3D cell cultures, cancer cells are grown in an environment that more closely mimics the 3D architecture and complexity of in vivo tumors. This approach has revolutionized cancer research by providing a more accurate representation of the tumor microenvironment (TME) and enabling the study of tumor behavior and response to therapies in a more physiologically relevant context. One of the key benefits of 3D cell culture in cancer research is the ability to recapitulate the complex interactions between cancer cells and their surrounding stroma. Tumors consist not only of cancer cells but also various other cell types, including stromal cells, immune cells, and blood vessels. These models bridge traditional 2D cell cultures and animal models, offering a cost-effective, scalable, and ethical alternative for preclinical research. As the field advances, 3D cell cultures are poised to play a pivotal role in understanding cancer biology and accelerating the development of effective anticancer therapies. This review article highlights the key advantages of 3D cell cultures, progress in the most common scaffold-based culturing techniques, pertinent literature on their applications in cancer research, and the ongoing challenges.
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    Biodegradable Magnesium Alloys for Biomedical Implants: Properties, Challenges, and Surface Modifications with a Focus on Orthopedic Fixation Repair
    (MDPI, 2023-12-19) Thomas, Kevin Koshy; Zafar, Mah Noor; Pitt, William G.
    Biomedical devices made from high-modulus and hardness materials play a critical role in enhancing the quality of life for people with bone-related ailments. While these materials have been successfully used in orthopedic applications, concerns including stress-shielding have necessitated the exploration of alternative solutions. An ideal biomedical implant requires a delicate balance of mechanical performance, corrosion resistance, tissue biocompatibility, and other properties such as tribological performance and osseointegration. This review explores the suitability of biodegradable magnesium (Mg) alloys as a promising material for biomedical implants. It delves into the essential properties of biomedical implants, emphasizing the importance of matching mechanical characteristics with human bone properties to mitigate stress shielding. The corrosion properties of implant materials are discussed, highlighting the need for controlled degradation to ensure the safety and longevity of implants. The focus then shifts to the potential of magnesium alloys as biomedical implants, examining their benefits, limitations, and the challenges associated with their high degradation rates and less-than-satisfactory mechanical properties. Alloying with elements such as aluminum, zinc, and others is explored to improve magnesium alloys’ mechanical performance and corrosion resistance. Furthermore, this review discusses surface modification techniques, including chemical conversion coatings and biomimetic deposition, as effective strategies to enhance the corrosion resistance and biocompatibility of magnesium and its alloys. These modifications offer opportunities to improve the long-term performance of magnesium-based biomedical implants. This review provides a comprehensive overview of the properties, challenges, and potential solutions associated with biodegradable magnesium alloys as a promising material for biomedical implants. It underscores the importance of addressing problems related to mechanical performance, corrosion resistance, and biocompatibility to advance the development of safe and effective biomedical implant materials.
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    Incorporating nanoparticles in 3D printed scaffolds for bone cancer therapy
    (Elsevier, 2023) AlSawaftah, Nour Majdi; Pitt, William G.; Husseini, Ghaleb
    The low occurrence rate of bone cancer contributes to delayed diagnosis and treatment; in addition, the surgical resection of bone tumors can cause significant bone defects, further hindering the effective treatment of the disease. 3D printing can help overcome some of these limitations by enabling the design and fabrication of innovative scaffolds loaded with chemotherapeutics and growth factors, stimulating bone regeneration, and delivering targeted cancer treatment. Moreover, advancements in nanotechnology have opened up new possibilities for bone tissue engineering. Nanoparticles (NPs) possess size-dependent physicochemical properties. NPs can also be designed to respond to specific stimuli enhancing localized drug delivery. These unique properties can be harnessed by embedding NPs in 3D-printed scaffolds to develop multifunctional bone scaffolds with enhanced mechanical properties and drug delivery capabilities. This review evaluates the impact of incorporating NPs in 3D-printed scaffolds on bone cancer therapy and bone regeneration. First, various 3D printing techniques employed in the biomedical field are presented and explained. The article then highlights notable achievements by researchers in this area. Finally, the review discusses the current obstacles facing this technology and how they can be addressed to enable translation into clinics.
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    Impact of Ionic Strength and Charge Density on Donnan Potential in the NaCl-Cation Exchange Membrane System
    (MDPI, 2023) Al-Sakaji, Baraa A. K.; Husseini, Ghaleb; Darwish, Naif
    This work aims to theoretically investigate the effect of both the fixed charge density of ion exchange membranes and the ionic strength of the treated aqueous NaCl solution on the generated Donnan potential at thermodynamic equilibrium conditions. The direct objective of our work is to calculate the equilibrium concentration of the Cl⁻ co-ion inside a swelled cation-exchange membrane equilibrated with a water/NaCl system. Two activity coefficient models are employed, i.e., the Debye–Huckel (DH) model (as a reference model) and the Meissner model, which is known for its applicability in treating concentrated solutions. Experimental data available in the literature for Donnan potential are used to verify model predictions. Our study confirms that a high fixed charge density is required to counterbalance the deterioration in membrane selectivity encountered in high-salinity systems. The DH model can be safely used to predict the Donnan potential for feed compositions up to 0.1 M. At higher compositions, the DH model significantly overestimates the predicted (absolute) Donnan potential compared to the Meissner model. The osmotic pressure resulting from the difference in ionic concentration between the membrane phase and the feed phase is found to have insignificant effects on the Donnan potential. The equilibrium computations and methodology are presented in a general way that enables handling multivalent electrolyte systems such as CaCl₂.
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    Effect of phospholipid head group on ultrasound‑triggered drug release and cellular uptake of immunoliposomes
    (Nature, 2023) Awad, Nahid S.; Paul, Vinod; AlSawaftah, Nour Majdi; Husseini, Ghaleb
    Liposomes are the most successful nanoparticles used to date to load and deliver chemotherapeutic agents to cancer cells. They are nano-sized vesicles made up of phospholipids, and targeting moieties can be added to their surfaces for the active targeting of specific tumors. Furthermore, Ultrasound can be used to trigger the release of the loaded drugs by disturbing their phospholipid bilayer structure. In this study, we have prepared pegylated liposomes using four types of phospholipids with similar saturated hydrocarbon tails including a phospholipid with no head group attached to the phosphate head (DPPA) and three other phospholipids with different head groups attached to their phosphate heads (DPPC, DPPE and DPPG). The prepared liposomes were conjugated to the monoclonal antibody trastuzumab (TRA) to target the human epidermal growth factor receptor 2 (HER2) overexpressed on HER2-positive cancer cells (HER2+). We have compared the response of the different formulations of liposomes when triggered with low-frequency ultrasound (LFUS) and their cellular uptake by the cancer cells. The results showed that the different formulations had similar size, polydispersity, and stability. TRA-conjugated DPPC liposomes showed the highest sensitivity to LFUS. On the other hand, incubating the cancer cells with TRA-conjugated DPPA liposomes triggered with LFUS showed the highest uptake of the loaded calcein by the HER2+ cells.