Nanoscale Drug Research Articles

Special Issue on Exploring Material Science and Technology Innovations

Materials science is one of the most dynamic areas of scientific research today, involving advanced nanotechnology and smart materials, and building on centuries of discovery, evolving from the early days of metallurgy. Each era of human civilization has been marked by the materials that define it—Bronze, Iron, Silicon—each enabling societies to develop tools, build infrastructure, and enhance their daily lives (Sass, 1998). Materials science was driven by trial and error. In ancient civilizations metals were produced by heating certain ores. These metals were used in tools, weapons, and building materials. This production continues in bronze age by combining copper and tin produced bronze, which have remarkable strangeness as compare to copper and tin. In next era human start new experiments with these materials like smelting and mixing and produce new materials for revolutionizing agriculture, warfare, and transportation (Smith, 1975, Callister and Rethwisch, 2020). The 20th century saw a transformation in the field, with the development of synthetic polymers, alloys, and composites, as well as the discovery of semiconductors that enabled the digital revolution. This period also marked the advent of materials science as a formal discipline, with researchers developing a deeper understanding of atomic structures and bonding mechanisms that could explain material properties. Today, advancements in nanotechnology allow scientists to manipulate materials at the atomic level, enabling the creation of materials with unprecedented properties and functionalities. A fundamental aim of materials scientist is innovation, understanding and controlling the properties of materials like mechanical, thermal, electrical, magnetic, and optical. Determine how materials interact with their environment and how they can be applied in various technology innovations. Materials are now engineered to exhibit specific properties tailored for distinct applications, ranging from ultralight yet strong aerospace components to flexible, conductive materials for wearable electronics. Materials with unique electrical properties, such as semiconductors, have revolutionized electronics, enabling the development of computers, smartphones, and other digital technologies. Similarly, materials with exceptional strength-to-weight ratios are essential in industries like automotive and aerospace, where reducing weight without compromising strength is crucial (Rao and Cheetham, 2001, Negahdary and Mabbott, 2025). Considering, the aim of materials scientist, special issue entitled “Exploring materials science and Technological Innovation” is planned. This enables researchers a unique platform to discuss and highlight innovations in nanomaterials such as carbon nanotubes, graphene, and quantum dots, which exhibit unique electrical, thermal, and mechanical properties. These materials are being applied across fields like medicine, where nanoscale drug delivery systems target disease sites directly, and electronics, where ultra-thin materials can lead to more powerful and energy-efficient devices. Biomaterials have revolutionized healthcare, offering possibilities for tissue engineering, regenerative medicine, and advanced medical devices. The advancements in the field of material science are such as allow for unprecedented control over material structure and composition for various interesting applications. The smart materials like piezoelectric materials that generate electricity when subjected to pressure—are opening new frontiers in robotics, automation, medical devices, and consumer and portable electronics devices. This issue showcased developments in materials/technologies related to sustainable development. The materials science is positioned to drive innovation in many domains for various applications. As the researchers are developing new compositions of materials with enhanced properties, such as higher strength, flexibility, conductivity, applications in renewable energy. The advance and sustainable materials, environment friendly manufacturing processes, and biodegradable polymers are expected to play key roles as the society strives for responsible resource management. The continued integration of computational methods will also be essential, allowing scientists to harness the power of big data to predict and model material behaviour more accurately. This special issue entitled “Exploring materials science and Technological Innovation” includes the article from national conference on exploring material science and technology innovations (NCEMSTI)-2024 that have platform for the importance of interdisciplinary collaboration, and open dialogue. Materials science will undoubtedly continue to evolve, shaping the future. Through continued exploration and innovation, this field will play a central role in building a sustainable, technologically advanced, and resilient world.

Abstract IA011: Strategies to close the translational gap for nanoscale drug delivery systems

Abstract Nanoscale drug delivery systems have enormous potential to leverage innovative chemistry and encapsulate a wide range of cargo. However, compared to the large number and diverse scope of nanoscale systems described in preclinical manuscripts, there are relatively few approved drug products representing a narrow range of chemistries. There are many reasons for this translational gap, ranging from manufacturing and regulatory challenges to clinical relevance and safety. This presentation outlines key strategies to address the multifaceted challenges that hinder the clinical adoption of nanoscale drug delivery systems. One of the first barriers is the difficulty of scaling up the production of nanoscale systems while maintaining quality and consistency. An illustrative case study will be shared of an approved nanotherapeutic becoming unavailable due to manufacturing concerns, and the resultant change in clinical practice. For a new investigational agent, the work required to optimize a promising nanoformulation is time-consuming and may not result in immediate, publishable findings, creating tension between essential translational work and projects more likely to yield high-profile publications and contribute to academic promotion. In the industry setting, successfully navigating this hurdle is likely to require significant capital, again without a guarantee of success. Without a stable and robust formulation that can be scaled for good manufacturing practice, the benefits of an innovative formulation cannot be fully realized. Another key principle underlying successful translation is identifying a clear clinical indication, which will guide clinical trial design and improve the likelihood of regulatory approval. Recent data suggest that national research funding trends heavily influence the focus of nanotechnology studies, resulting in a misalignment between clinical needs and the investigational agents being developed. In the future, a funding re-alignment may open additional opportunities for basket trials in patient populations lacking a standard of care, or in diseases where the current treatment options are highly toxic. Expanding the clinical indications for nanotherapeutics will likely require academic-industry partnerships to bring together a robust drug product and a strong clinical rationale. The regulatory process for nanoscale therapeutics is evolving, making early communication between investigators and regulators crucial for successfully transitioning nanoscale drug delivery systems from the lab to clinical use for cancer patients. Citation Format: Joelle P. Straehla. Strategies to close the translational gap for nanoscale drug delivery systems [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr IA011.

Glycyrrhizic acid-based multifunctional nanoplatform for tumor microenvironment regulation.

Natural compounds demonstrate unique therapeutic advantages for cancer treatment, primarily through direct tumor suppression or interference with the tumor microenvironment (TME). Glycyrrhizic acid (GL), a bioactive ingredient derived from the medicinal herb Glycyrrhiza uralensis Fisch., and its sapogenin glycyrrhetinic acid (GA), have been recognized for their ability to inhibit angiogenesis and remodel the TME. Consequently, the combination of GL with other therapeutic agents offers superior therapeutic benefits. Given GL's amphiphilic structure, self-assembly capability, and liver cancer targeting capacity, various GL-based nanoscale drug delivery systems have been developed. These GL-based nanosystems exhibit angiogenesis suppression and TME regulation properties, synergistically enhancing anti-cancer effects. This review summarizes recent advances in GL-based nanosystems, including polymer-drug micelles, drug-drug assembly nanoparticles (NPs), liposomes, and nanogels, for cancer treatment and tumor postoperative care, providing new insights into the anti-cancer potential of natural compounds. Additionally, the review discusses existing challenges and future perspectives for translating GL-based nanosystems from bench to bedside.

Nano - Based Therapeutic Strategies in Management of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease, progressively distinctive via cartilage destruction, auto-antibody production, severe joint pain, and synovial inflammation. Nanotechnology represents as one of the utmost promising scientific technologies of the 21st century. It exhibits remarkable potential in the field of medicine, including imaging techniques and diagnostic tools, drug delivery systems and providing advances in treatment of several diseases with nanosized structures (less than 100 nm). Conventional drugs as a cornerstone of RA management including disease-modifying antirheumatic drugs (DMARDS), Glucocorticosteroids, etc are under clinical practice. Nevertheless, their low solubility profile, poor pharmacokinetics behaviour, and non-targeted distribution not only hamper their effectiveness, but also give rise to severe adverse effects which leads to the need for the emergence of nanoscale drug delivery systems. Several types of nano-diagnostic agents and nanocarriers have been identified; including polymeric nanoparticles (NPs), liposomes, nanogels, metallic NPs, nanofibres, carbon nanotubes, nano fullerene etc. Various patents and clinical trial data have been reported in relevance to RA treatment. Nanocarriers, unlike standard medications, encapsulate molecules with high drug loading efficacy and avoid drug leakage and burst release before reaching the inflamed sites. Because of its enhanced targeting specificity with the ability to solubilise hydrophobic drugs, it acts as an enhanced drug delivery system. This study explores nanoparticles potential role in RA as a carrier for site-specific delivery and its promising strategies to overcome the drawbacks. Hence, it concludes that nanomedicine is advantageous compared with conventional therapy to enhanced futuristic approach.

Cisplatin-encapsulated TRAIL-engineered exosomes from human chorion-derived MSCs for targeted cervical cancer therapy

BackgroundCisplatin (DDP) is an efficacious and widely applied chemotherapeutic drug for cervical cancer patients who are diagnosed as metastatic and inoperable, or desiring fertility preservation. Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) selectively triggers cancer cells apoptosis by binding to cognate death receptors (DR4 and DR5). Mesenchymal stem cells-derived exosomes (MSCs-Exo) have been regarded as ideal drug carriers on account of their nanoscale, low toxicity, low immunogenicity, high stability, biodegradability, and abundant sources.MethodsHuman chorion-derived mesenchymal stem cells (hCD-MSCs) were isolated by adherent culture method. TRAIL-engineered hCD-MSCs (hCD-MSCsTRAIL) were constructed by lentivirus transfection, and its secreted Exo (hCD-MSCs-ExoTRAIL) were acquired by differential centrifugation and confirmed to overexpress TRAIL by western blotting. Next, nanoscale drug delivery systems (DDP & hCD-MSCs-ExoTRAIL) were fabricated by loading DDP into hCD-MSCs-ExoTRAIL via electroporation. The CCK-8 assay and flow cytometry were conducted to explore the proliferation and apoptosis of cervical cancer cells (SiHa and HeLa), respectively. Cervical cancer-bearing nude mice were constructed to examine the antitumor activity and biosafety of DDP & hCD-MSCs-ExoTRAIL in vivo.ResultsCompared with hCD-MSCs-Exo, hCD-MSCs-ExoTRAIL weakened proliferation and enhanced apoptosis of cervical cancer cells. DDP & hCD-MSCs-ExoTRAIL were proved to retard cervical cancer cell proliferation and propel cell apoptosis more effectively than DDP or hCD-MSCs-ExoTRAIL alone in vitro. In cervical cancer-bearing mice, DDP & hCD-MSCs-ExoTRAIL evidently hampered tumor growth, and its role in inducing apoptosis was mechanistically associated with JNK/p-c-Jun activation and survivin suppression. Moreover, DDP & hCD-MSCs-ExoTRAIL showed favorable biosafety in vivo.ConclusionsDDP & hCD-MSCs-ExoTRAIL nanoparticles exhibited great promise for cervical cancer treatment as an Exo-based chemo-gene combinational therapy in clinical practice.Graphical abstract

Recent Advances in Cyclodextrin-Based Nanoscale Drug Delivery Systems.

Cyclodextrins (CDs) belong to a class of cyclic oligosaccharides characterized by their toroidal shape consisting of glucose units linked via α-1,4-glycosidic bonds. This distinctive toroidal shape exhibits a dual nature, comprising a hydrophobic interior and a hydrophilic exterior, making CDs highly versatile in various pharmaceutical products. They serve multiple roles: they act as solubilizers, stabilizers, controlled release promoters, enhancers of drug bioavailability, and effective means of masking undesirable tastes and odors. Taking advantage of these inherent benefits, CDs have been integrated into numerous nanoscale drug delivery systems. The resulting nanomaterials exploit the exceptional properties of CDs, including their ability to solubilize hydrophobic drugs for substantial drug loading, engage in supramolecular complexation for engineered nanomaterials, increase bioavailability for improved therapeutic efficacy, stabilize labile drugs, and exhibit biocompatibility and versatility. This paper compiles recent studies on CD functional nanoscale drug delivery platforms. First, we described the physicochemical and toxicological aspects of CDs, CD/drug inclusion complexation, and their impact on improving drug bioavailability. We then summarized applications for CD-functional nano delivery systems based on polymeric, hybrid, lipid-based nanoparticles, and CD-based nanofibers. Particular interest was in the targeted applications and the function of the CD molecules used. In most applications, CD molecules were used for drug solubilization and loading, while in some studies, CD molecules were employed for supramolecular complexation to construct nanoscale drug delivery systems. Finally, the review concludes with a thoughtful consideration of the current challenges and outlook.

Eradication of Large Tumors by Nanoscale Drug Self-Assembly.

Most patients with cancer are first diagnosed at an advanced disease stage, when tumors are already large and/or metastases are present. This circumstance has a negative impact on the prognosis and therapeutic effect of anticancer drugs. In this study, it is demonstrated that photosensitizer chlorin e6 and the photochemotherapy drug mitoxantrone self-assemble into relatively stable nanoassemblies (CM NAs) through hydrogen-bonding effect, π-π stacking, and hydrophobic interactions. Administration of CM NAs in combination with 660nm laser irradiation shows chemotherapeutic, photothermal, and photodynamic effects, causing tumor cell apoptosis and pyroptosis and enabling noninvasive tumor ablation without compromising the surrounding normal tissue. More importantly, treatment with CM NAs increases tumor immunogenicity, leading to a strong and long-term antitumor immune response that eradicates large tumors and provides long-term protection against tumor recurrence on various tumor models.

Advances in Proniosomes: Harnessing Nanotechnology for Enhanced Drug Delivery

In recent years, the field of drug delivery has experienced remarkable progress as researchers strive to enhance the efficacy and safety of pharmaceutical treatments while ensuring patient convenience and compliance. One notable innovation that has garnered significant attention is the development of proniosomes. Proniosomes represent a novel drug delivery platform that merges the advantageous features of niosomes and liposomes while effectively addressing their inherent limitations. Unlike traditional liquid-based liposomes and niosomes, proniosomes are formulated as dry, free-flowing powders or granules. This dry presentation offers several key benefits, including improved stability during storage and transportation, reducing the risk of drug degradation and extending shelf life. Upon contact with an appropriate medium, such as body fluids or a dispersion medium, these proniosomes readily transform into niosomal structures. This characteristic transformation ensures the controlled release of the encapsulated drug, leading to prolonged drug action and potentially reduced dosing frequency, enhancing patient adherence to therapy. Central to the success of proniosomes is the application of nanotechnology, a discipline focused on manipulating materials at the nanoscale. By leveraging nanotechnology, researchers have achieved significant improvements in the physicochemical properties and drug-loading capabilities of proniosomes. Nanoscale drug carriers can traverse biological barriers more effectively, leading to improved bioavailability and targeted delivery to specific tissues or cells. The purpose of this review article is to provide a comprehensive overview of the recent advances in proniosomes and their application in harnessing nanotechnology for enhanced drug delivery.

Tunable supramolecular self-assemblies based on cyclodextrin polymer as a loading platform for water-soluble drugs

Drug loading capacity is a crucial character of nano-scaled drug carriers to achieve high quality pharmaceutical preparations. However, efficient encapsulation of water-soluble small molecular drugs still faces large obstacles in many cases. Herein, we designed a novel supramolecular delivery system constructed by poly(β-cyclodextrin) containing benzoic acid groups (PCD-PA) and adamantyl terminated poly(ethylene glycol) (PEG-AD) to provide multiple intermolecular interactions for competent loading of water-soluble small-molecular drugs. PCD-PA had multiple host molecules, and PEG-AD could be inserted via host-guest interaction in different proportion to adjust the composition of supramolecular carrier. Meanwhile, π-π stacking and electrostatic interaction furnished by benzoic acid groups served as binding force for drug entrapment, which led to considerable loading capacity for several water-soluble drugs. Among the drugs with different chemical structures, mitoxantrone hydrochloride and doxorubicin hydrochloride bearing anthraquinone rings and several protonable amino groups acquired the highest loading content as about 14 % in PCD-PA3/PEG-AD supramolecular self-assemblies. Further computational simulations investigated the mechanism of drug loading based on the interactions between the carrier materials and the payloads. In addition, the weakly acidic environment obviously accelerated the release of certain drugs. All in all, this self-assembled supramolecular nano-system displayed great potentials as a delivery platform for diverse water-soluble drugs.

Ellagic acid-enhanced biocompatibility and bioactivity in multilayer core-shell gold nanoparticles for ameliorating myocardial infarction injury

BackgroundMyocardial infarction (MI) is the main contributor to most cardiovascular diseases (CVDs), and the available post-treatment clinical therapeutic options are limited. The development of nanoscale drug delivery systems carrying natural small molecules provides biotherapies that could potentially offer new treatments for reactive oxygen species (ROS)-induced damage in MI. Considering the stability and reduced toxicity of gold-phenolic core-shell nanoparticles, this study aims to develop ellagic acid-functionalized gold nanoparticles (EA-AuNPs) to overcome these limitations.ResultsWe have successfully synthesized EA-AuNPs with enhanced biocompatibility and bioactivity. These core-shell gold nanoparticles exhibit excellent ROS-scavenging activity and high dispersion. The results from a label-free imaging method on optically transparent zebrafish larvae models and micro-CT imaging in mice indicated that EA-AuNPs enable a favorable excretion-based metabolism without overburdening other organs. EA-AuNPs were subsequently applied in cellular oxidative stress models and MI mouse models. We found that they effectively inhibit the expression of apoptosis-related proteins and the elevation of cardiac enzyme activities, thereby ameliorating oxidative stress injuries in MI mice. Further investigations of oxylipin profiles indicated that EA-AuNPs might alleviate myocardial injury by inhibiting ROS-induced oxylipin level alterations, restoring the perturbed anti-inflammatory oxylipins.ConclusionsThese findings collectively emphasized the protective role of EA-AuNPs in myocardial injury, which contributes to the development of innovative gold-phenolic nanoparticles and further advances their potential medical applications.Graphical

Construction of anticancer drug incorporated aptamer-functionalized cationic β-lactoglobulin: induction of cell cycle arrest and apoptosis in colorectal cancer

Nanoscale drug delivery systems that are both multifunctional and targeted have been developed using proteins as a basis, thanks to their attractive biomacromolecule properties. A novel nanocarrier, aptamer (AS1411)-conjugated β-lactoglobulin/poly-l-lysine (BLG/Ap/PL) nanoparticles, was developed in this study. To this unique formulation, the as-prepared nanocarrier blends the distinctive features of an aptamer as a chemotherapeutic targeting agent with those of protein nanocarriers. By loading cabazitaxel (CTX) onto the nanocarriers, the therapeutic potential of BLG/Ap/PL could be demonstrated. The CTX-loaded BLG/Ap/PL (CTX@BLG/Ap/PL) showed a regulated drug release profile in an acidic milieu, which could improve therapeutic efficacy in cancer cells and have a high drug encapsulation efficacy of up to 93%. However, compared to free CTX, CTX@BLG/Ap/PL killed colorectal HCT116 cancer cells with a higher efficacy at 24 and 48 h. Further investigation confirms the apoptosis by acridine orange and ethidium bromide (AO/EB), and DAPI staining confirms the morphological changes, chromatin condensation, and membrane blebbing in the treated cell through flow cytometry displayed the release of higher percentages of apoptosis. Cell cycle analysis revealed that CTX@BLG/Ap/PL induced sub-G1 and G2/M phase (apoptosis) at 24 and 48 h. Annexin V/propidium iodide (PI) flow cytometry analysis confirmed that CTX@BLG/Ap/PL induces apoptosis in HCT116 cells. Overall, this study proved that CTX@BLG/Ap/PL had several advantages over free chemotherapeutic drugs and showed promise as a solution to the clinical problems associated with targeted antitumor drug delivery systems.

Nanomedicine and Targeted Drug Delivery: Advances and Challenges

Nanomedicine, the application of nanotechnology to medicine, has revolutionized the field by providing novel approaches to diagnosing, treating, and preventing diseases. Among its various applications, targeted drug delivery has emerged as a key area of focus, offering the potential to enhance therapeutic efficacy and minimize side effects by directing drugs specifically to diseased cells or tissues. This review discusses the latest advancements in nanomedicine, particularly in the design and development of nanoscale drug delivery systems such as liposomes, polymeric nanoparticles, dendrimers, and inorganic nanoparticles. We explore the mechanisms of passive and active targeting, as well as stimuli-responsive delivery systems. Clinical applications in cancer therapy, cardiovascular diseases, neurological disorders, and infectious diseases are examined to illustrate the practical impact of these technologies. Furthermore, we address the challenges facing the field, including toxicity and biocompatibility concerns, manufacturing and scalability issues, regulatory and ethical considerations, and the integration of personalized medicine approaches. By providing a comprehensive overview of the current state and future directions of nanomedicine and targeted drug delivery, this review aims to highlight the transformative potential of these technologies in improving patient outcomes and advancing healthcare. Keywords: Nanomedicine, Targeted drug delivery, Liposomes, Passive targeting, Personalized medicine

Reverse Gradient Distributions of Drug and Polymer Molecules within Electrospun Core-Shell Nanofibers for Sustained Release.

Core-shell nanostructures are powerful platforms for the development of novel nanoscale drug delivery systems with sustained drug release profiles. Coaxial electrospinning is facile and convenient for creating medicated core-shell nanostructures with elaborate designs with which the sustained-release behaviors of drug molecules can be intentionally adjusted. With resveratrol (RES) as a model for a poorly water-soluble drug and cellulose acetate (CA) and PVP as polymeric carriers, a brand-new electrospun core-shell nanostructure was fabricated in this study. The guest RES and the host CA molecules were designed to have a reverse gradient distribution within the core-shell nanostructures. Scanning electron microscope and transmission electron microscope evaluations verified that these nanofibers had linear morphologies, without beads or spindles, and an obvious core-shell double-chamber structure. The X-ray diffraction patterns and Fourier transform infrared spectroscopic results indicated that the involved components were highly compatible and presented in an amorphous molecular distribution state. In vitro dissolution tests verified that the new core-shell structures were able to prevent the initial burst release, extend the continuous-release time period, and reduce the negative tailing-off release effect, thus ensuring a better sustained-release profile than the traditional blended drug-loaded nanofibers. The mechanism underlying the influence of the new core-shell structure with an RES/CA reverse gradient distribution on the behaviors of RES release is proposed. Based on this proof-of-concept demonstration, a series of advanced functional nanomaterials can be similarly developed based on the gradient distributions of functional molecules within electrospun multi-chamber nanostructures.

Nanocarriers' repartitioning of drugs between blood subcompartments as a mechanism of improving pharmacokinetics, safety, and efficacy

For medical emergencies, such as acute ischemic stroke, rapid drug delivery to the target site is essential. For many small molecule drugs, this goal is unachievable due to poor solubility that prevents intravenous administration, and less obviously, by extensive partitioning to plasma proteins and red blood cells (RBCs), which greatly slows delivery to the target. Here we study these effects and how they can be solved by loading into nanoscale drug carriers. We focus on fingolimod, a small molecule drug that is FDA-approved for treatment of multiple sclerosis, which has also shown promise in the treatment of stroke. Unfortunately, fingolimod has poor solubility and very extensive partitioning to plasma proteins and RBCs (in whole blood, 86% partitions to RBCs, 13.96% to plasma proteins, and 0.04% is free). We develop a liposomal formulation that slows the partitioning of fingolimod to RBCs and plasma proteins, enables intravenous delivery, and additionally prevents fingolimod toxicity to RBCs. The liposomal formulation nearly completely prevented fingolimod adsorption to plasma proteins (association with plasma proteins was 98.4 ± 0.4% for the free drug vs. 5.6 ± 0.4% for liposome-loaded drug). When incubated with whole blood in vitro, the liposomal formulation greatly slowed partitioning of fingolimod to RBCs and also eliminated deleterious effects of fingolimod on RBC rigidity, morphology, and hemolysis. In vivo, the liposomal formulation delayed fingolimod partitioning to RBCs for over 30 min, a critical time window for stroke. Fingolimod-loaded liposomes showed improved efficacy in a mouse model of post-stroke neuroinflammation, completely sealing the leaky blood-brain barrier (114 ± 11.5% reduction in albumin leak into the brain for targeted liposomes vs. 38 ± 16.5% reduction for free drug). This effect was only seen for liposomes modified with antibodies to enable targeted delivery to the site of action, and not in unmodified, long-circulating liposomes. Thus, loading fingolimod into liposomes prevented partitioning to RBCs and associated toxicities and enabled targeted delivery. This paradigm can be used for tuning the blood distribution of small molecule drugs for the treatment of acute illnesses requiring rapid pharmacologic intervention.

The electro-responsive nanoliposome as an on-demand drug delivery platform for epilepsy treatment

Nano-based drug delivery systems are regarded as a promising tool for efficient epilepsy treatment and seizure medication with the least general side effects and socioeconomic challenges. In the current study, we have designed a smart nanoscale drug delivery platform and applied it in the kindling model of epilepsy that is triggered rapidly by epileptic discharges and releases anticonvulsant drugs in situ, such as carbamazepine (CBZ). The CBZ-loaded electroactive ferrocene nanoliposomes had an average diameter of 100.6 nm, a surface charge of −7.08 mV, and high drug encapsulation efficiency (85.4 %). A significant increase in liposome size was observed in response to direct current (50–500 μA) application. This liposome-based drug delivery system can release CBZ at a fast rate in response to both direct current and pulsatile electrical stimulation in vitro. The CBZ-liposome can release the anticonvulsant drug upon epileptiform activity in the kindled rat model and can decline electrographic and behavioral seizure activity in response to electrical stimulation of the hippocampus with an initially subconvulsive current. With satisfactory biosafety results, this “smart” nanocarrier has promising potential as an effective and safe drug delivery system to improve the therapeutic index of antiepileptic drugs.

Loading co-amorphous on Metal-Organic Frameworks for gelation elimination and anti-cancer drug delivery enhancement

Troublesome gelation occurring during the dissolution of special co-amorphous (COAM) systems poses a limitation on their further applications. Metal-Organic Frameworks (MOFs) are promising porous materials for nano-scale drug delivery due to their high loading capacity and ability to control drug release. Examples of MOFs as drug carriers with the confinement effect for COAM drugs have never been reported. In this study, to eliminate the gelation of the COAM of an anti-cancer drug gefitinib (GTB) and co-former saccharin (SAC) for enhancing their anti-cancer drug delivery, a Zr-based MOF, nanoUiO-67, was selected as drug carrier. The loading process of GTB-SAC COAM on nanoUiO-67 was revealed via a real-time spinning disk confocal fluorescence microscope. The maintenance of molecular interactions between GTB and SAC in GTB-SAC COAM after loaded on nanoUiO-67 was proven experimentally and computationally, along with the host (nanoUiO-67)-guest (drug) interactions. The combined advantages of porous materials nanoMOFs and GTB-SAC COAM were fully demonstrated in terms of excellent physical stability, desirable drug release, good bio-compatibility and higher cytotoxicity towards HeLa cells. It is expected that this novel strategy could have potential application in gelation elimination and developing multi-component drug-loaded MOFs.

Nanosponges-Road Less Explored Changing Drug Delivery Approach: An Explicative Review.

Nanotechnology exhibits a wide range of applications in the domain of disease therapy, diagnosis, biological detection, and environmental safeguards. The cross-linked polymeric nanosponges (NSs) are a nanoscale drug carrier system with a 3D porous structure and high entrapment efficacy. NSs up to the fourth generation are currently accessible and can serve as a delivery system for both hydrophilic and hydrophobic drugs. The delivery system exhibits superiority over alternative methods due to its ability to achieve controlled and targeted drug delivery. The colloidal structure of NSs facilitates the encapsulation of a wide range of agents such as proteins and peptides, enzymes, antineoplastic drugs, volatile oil, vaccines, DNA, etc. NSs efficiently overcome the challenges associated with drug toxicity and poor aqueous solubility. NS formulations have been explored for various applications like gaseous encapsulation, enzyme immobilization, antifungal therapy, poison absorbent, water purification, etc. This review provides a comprehensive analysis regarding methods of synthesis, distinct polymeric NSs, mechanism of drug release, factors affecting NS development, applications, and patents filed in the field of NSs. Herein, the recently developed NS formulations, their potential in cancer therapy, and current progressions of NS for SARS-CoV-2 management are also deliberated with special attention, focusing on the significant challenges and future directions.

A comparative investigation of release kinetics of paclitaxel from natural protein and macromolecular nanocarriers in nanoscale drug delivery systems

Understanding the release behaviour of nanodrugs is a crucial step to better assess and control therapeutic outcomes and unfavourable side effects. Herein, we report a systematic study comparing the release kinetics and thermodynamics of paclitaxel (PTX) from supramolecularly assembled sub-micron particles based on natural macromolecules such as zein, whey, casein, bovine serum albumin (BSA) and conventional stabilizers such as pluronic F-127 (poloxamer 407), and β-cyclodextrin (β-CD) to gain insights into the role of carrier chemistry. For this purpose, nanomedicines with statistically indifferent sizes —in the range of 191.0 ± 0.8 nm (BSA) to 243.3 ± 11.6 nm (zein) were prepared (p > 0.05). The zeta potential values ranged from −3.2 ± 1.1 mV (pluronic F-127) to −17.2 ± 1.8 mV (whey) in phosphate buffered saline. The type of nanocarrier significantly influenced the long-term steady-state plateau of the release, resulting in a cumulative release of 70.3 ± 2.0 % of PTX from casein (the highest) and 46.8 ± 4.7 % of PTX from zein (the lowest). Time-resolved release data were analysed with various kinetical models, encompassing zero-order, first-order, Higuchi, Peppas-Sahlin, and Korsmeyer-Peppas kinetics. The analysis revealed that the Korsmeyer-Peppas model best captured the data. For these nanomedicines, the half-life of the encapsulated drugs was found to be 106.4 ± 31.3 h (zein), 4.7 ± 1.2 h (whey), 10.7 ± 1.8 h (pluronic F-127), 6.4 ± 0.9 h (casein), 10.8 ± 3.2 h (β-CD), and 4.0 ± 1.0 h (BSA). TEM characterization revealed differences in the macromolecular arrangement of the active ingredient within these nanocarriers, in addition to the structural differences among the various encapsulating agents. These differences manifested as variations in the internal nanostructures, leading to the creation of distinct microenvironments that could either facilitate or impede the movement of PTX molecules through the encapsulant matrices. In clinical settings, such fine details of nanocarrier design are important: by choosing the most appropriate nanocarrier (or their mixtures), clinicians can fine-tune drug administration to obtain the intended therapeutic window while mitigating the risk of potential negative reactions.

WITHDRAWN: Folic acid Grafted, cell-penetrating peptide conjugated pH-sensitive hydrophobically modified Glycol chitosan nanoparticles for drug delivery in breast cancer

Nanocarriers are an outcome of the fast development of nanotechnology; however, delivering drugs to tumor sites effectively is still a major difficulty. A pH-responsive drug carrier with good cell penetration and targeting ability was developed to release the drug exactly to the cancer site and overcome these limitations.The drug carrier FA-TAT-HGCNPs/PTX, which is pH-responsive, uses folic acid (FA) and TAT peptide to deliver paclitaxel (PTX) for target folate-receptor-overexpressing breast cancer cells. 2-(diisopropylamino) ethyl methacrylate was connected to glycol chitosan (GC) to form HGCNPs. Then TAT and HGCNPs were conjugated and FA was grafted onto the HGCNPs’ hydroxyl group. Physicochemical characterizations of FA-TAT-HGCNPs was also evaluated. The maximum DLE and EE values of the FA-TAT-HGCNPs at pH 8.0 were 74.0 ± 2.22 % and 93.7 ± 2.8 %, respectively. FA-TAT-HGCNPs, for instance, showed stability during long-term storage and lyophilization while exhibiting pH-responsive dissociation properties. The synthesized drug carrier was characterized by FTIR, XRD, SEM, HRTEM, DLS, and Zeta analysis. MTT assay exhibited the high anticancer activity of the FA-TAT-HGCNPs/PTX against the MCF-7 cells, whereas drug-free ones are highly biocompatible. The pharmacokinetic results showed twice the bioavailability of FA-TAT-HGCNPs/PTX compared to HGCNPs/PTX. Unlike FA-HGCNPs/PTX, CLSM analysis showed that FA-TAT-HGCNPs/PTX had a significantly more efficient intracellular uptake in MCF-7 cells. These data have shown the transmembrane ability of TATpeptide,the targeting effects of folate decoration, and the synergistic interaction between them.According to these findings, PTX-loaded FA-TAT-HGCNPs offer a potentially effective nanoscale drug delivery system for the treatment of breast cancer.

Nanostructure-Mediated Transport of Therapeutics through Epithelial Barriers.

The ability to precisely treat human disease is facilitated by the sophisticated design of pharmacologic agents. Nanotechnology has emerged as a valuable approach to creating vehicles that can specifically target organ systems, effectively traverse epithelial barriers, and protect agents from premature degradation. In this review, we discuss the molecular basis for epithelial barrier function, focusing on tight junctions, and describe different pathways that drugs can use to cross barrier-forming tissue, including the paracellular route and transcytosis. Unique features of drug delivery applied to different organ systems are addressed: transdermal, ocular, pulmonary, and oral delivery. We also discuss how design elements of different nanoscale systems, such as composition and nanostructured architecture, can be used to specifically enhance transepithelial delivery. The ability to tailor nanoscale drug delivery vehicles to leverage epithelial barrier biology is an emerging theme in the pursuit of facilitating the efficacious delivery of pharmacologic agents.