Nanoparticle-mediated Drug Delivery System Research Articles

Bioinspired Adaptive Microdrugs Enhance the Chemotherapy of Malignant Glioma: Beyond Their Nanodrugs.

Solid nanoparticle-mediated drug delivery systems are usually confined to nanoscale due to the enhanced permeability and retention effect. However, they remain a great challenge for malignant glioma chemotherapy because of poor drug delivery efficiency and insufficient tumor penetration resulting from the blood-brain barrier/blood-brain tumor barrier (BBB/BBTB). Inspired by biological microparticles (e.g., cells) with excellent adaptive deformation, it is demonstrated that the adaptive microdrugs (even up to 3.0µm in size) are more efficient than their nanodrugs (less than 200nm in size) to cross BBB/BBTB and penetrate into tumor tissues, achieving highly efficient chemotherapy of malignant glioma. The distinct delivery of the adaptive microdrugs is mainly attributed to the enhanced interfacial binding and endocytosis via adaptive deformation. As expected, the obtained adaptive microdrugs exhibit enhanced accumulation, deep penetration, and cellular internalization into tumor tissues in comparison with nanodrugs, significantly improving the survival rate of glioblastoma mice. It is believed that the bioinspired adaptive microdrugs enable them to efficiently cross physiological barriers and deeply penetrate tumor tissues for drug delivery, providing an avenue for the treatment of solid tumors.

Nanoparticle-Mediated Drug Delivery Systems for Precision Targeting in Oncology.

Nanotechnology has emerged as a transformative force in oncology, facilitating advancements in site-specific cancer therapy and personalized oncomedicine. The development of nanomedicines explicitly targeted to cancer cells represents a pivotal breakthrough, allowing the development of precise interventions. These cancer-cell-targeted nanomedicines operate within the intricate milieu of the tumour microenvironment, further enhancing their therapeutic efficacy. This comprehensive review provides a contemporary perspective on precision cancer medicine and underscores the critical role of nanotechnology in advancing site-specific cancer therapy and personalized oncomedicine. It explores the categorization of nanoparticle types, distinguishing between organic and inorganic variants, and examines their significance in the targeted delivery of anticancer drugs. Current insights into the strategies for developing actively targeted nanomedicines across various cancer types are also provided, thus addressing relevant challenges associated with drug delivery barriers. Promising future directions in personalized cancer nanomedicine approaches are delivered, emphasising the imperative for continued optimization of nanocarriers in precision cancer medicine. The discussion underscores translational research's need to enhance cancer patients' outcomes by refining nanocarrier technologies in nanotechnology-driven, site-specific cancer therapy.

Nanoparticle Mediated Drug Delivery Systems for Cancer Management

Nanoparticle Mediated Drug Delivery Systems for Cancer Management

Potential of Nano-Antioxidants and Nanomedicine for Recovery from Neurological Disorders Linked to Long COVID Syndrome.

Long-term neurological complications, persisting in patients who cannot fully recover several months after severe SARS-CoV-2 coronavirus infection, are referred to as neurological sequelae of the long COVID syndrome. Among the numerous clinical post-acute COVID-19 symptoms, neurological and psychiatric manifestations comprise prolonged fatigue, "brain fog", memory deficits, headache, ageusia, anosmia, myalgias, cognitive impairments, anxiety, and depression lasting several months. Considering that neurons are highly vulnerable to inflammatory and oxidative stress damages following the overproduction of reactive oxygen species (ROS), neuroinflammation and oxidative stress have been suggested to dominate the pathophysiological mechanisms of the long COVID syndrome. It is emphasized that mitochondrial dysfunction and oxidative stress damages are crucial for the pathogenesis of neurodegenerative disorders. Importantly, antioxidant therapies have the potential to slow down and prevent disease progression. However, many antioxidant compounds display low bioavailability, instability, and transport to targeted tissues, limiting their clinical applications. Various nanocarrier types, e.g., liposomes, cubosomes, solid lipid nanoparticles, micelles, dendrimers, carbon-based nanostructures, nanoceria, and other inorganic nanoparticles, can be employed to enhance antioxidant bioavailability. Here, we highlight the potential of phytochemical antioxidants and other neuroprotective agents (curcumin, quercetin, vitamins C, E and D, melatonin, rosmarinic acid, N-acetylcysteine, and Ginkgo Biloba derivatives) in therapeutic strategies for neuroregeneration. A particular focus is given to the beneficial role of nanoparticle-mediated drug-delivery systems in addressing the challenges of antioxidants for managing and preventing neurological disorders as factors of long COVID sequelae.

Meet the First Authors.

Meet the First Authors.

Rationalizing the Use of Polyphenol Nano-formulations in the Therapy of Neurodegenerative Diseases.

Neurodegenerative diseases are a heterogeneous group of disorders among aging populations worldwide characterized by the progressive degeneration of the structure and function of brain cells and the nervous system. Alzheimer's disease and Parkinson's disease are common neurodegenerative diseases (NDs). Classic pathological features of AD are the accumulation of the amyloid betaprotein and aggregates of hyperphosphorylated tau protein around the brain cells. Dopaminergic neuronal death in the midbrain and accumulation of α- synuclein in the neurons are the hallmark of Parkinson's disease. The pathogenesis is multifactorial, and both neurodegenerative disorders have complex etiology. Oxidative stress closely linked with mitochondrial dysfunction, excitotoxicity, nitric oxide toxicity, and neuro-inflammation, is anticipated to trigger neuronal death. Ample evidence has implicated that oxidative stress and inflammation contribute to the pathology of neurodegeneration in AD and PD. Currently, acetylcholinesterase inhibitors are the main treatment option for AD, while L-DOPA is the gold standard therapy for PD. Along with the main therapy, many endogenous antioxidants, like vitamin E, selenium, etc., are also given to the patients to combat oxidative stress. Current treatment for these NDs is limited due to the blood-brain barrier (BBB) that hinders drug targeting towards neurons. In this review, we emphasize adjunct treatment with anti-inflammatory agents that act at the site of the disease and can halt the disease progression by attenuating the effect of ROS triggering neuro-inflammatory response. Polyphenols, either as purified compounds or extracts from various natural plant sources, have been well studied and documented for anti-inflammatory effects, but their use for ND is limited due to their physicochemical attributes. Nanoparticle-mediated drug delivery system exhibits immense potential to overcome these hurdles in drug delivery to the CNS, enabling nanoparticle-based therapies to directly target the inflammation and release bioactive compounds with anti-inflammatory properties to the site of action.

ADAM9-Responsive Mesoporous Silica Nanoparticles for Targeted Drug Delivery in Pancreatic Cancer.

Simple SummaryThe clinical efficacy of systemic chemotherapy is limited in pancreatic cancer (PDAC) due to toxicity-dependent dose-limitations often leading to premature cessation of therapy. Targeted delivery of chemotherapeutic drugs to cancer cells, without affecting healthy nontumor cells, will largely reduce collateral toxicity. Reductions in collateral toxicity will allow increased drug concentrations to be used, thereby increasing the efficacy of chemotherapy. In the current study, we designed and validated a PDAC-specific protease-dependent drug release system. More specifically, we generated capped mesoporous silica nanoparticles that only release their cargo after proteolytic removal of the cap by PDAC-expressed proteases. We demonstrated the feasibility of protease-mediated targeted drug delivery in PDAC through the release of paclitaxel, resulting in cytotoxicity in cultured PDAC cells.Pancreatic ductal adenocarcinoma (PDAC) has the worst survival rate of all cancers. This poor prognosis results from the lack of efficient systemic treatment regimens, demanding high-dose chemotherapy that causes severe side effects. To overcome dose-dependent toxicities, we explored the efficacy of targeted drug delivery using a protease-dependent drug-release system. To this end, we developed a PDAC-specific drug delivery system based on mesoporous silica nanoparticles (MSN) functionalized with an avidin–biotin gatekeeper system containing a protease linker that is specifically cleaved by tumor cells. Bioinformatic analysis identified ADAM9 as a PDAC-enriched protease, and PDAC cell-derived conditioned medium efficiently cleaved protease linkers containing ADAM9 substrates. Cleavage was PDAC specific as conditioned medium from leukocytes was unable to cleave the ADAM9 substrate. Protease linker-functionalized MSNs were efficiently capped with avidin, and cap removal was confirmed to occur in the presence of PDAC cell-derived ADAM9. Subsequent treatment of PDAC cells in vitro with paclitaxel-loaded MSNs indeed showed high cytotoxicity, whereas no cell death was observed in white blood cell-derived cell lines, confirming efficacy of the nanoparticle-mediated drug delivery system. Taken together, this research introduces a novel ADAM9-responsive, protease-dependent, drug delivery system for PDAC as a promising tool to reduce the cytotoxicity of systemic chemotherapy.

A comprehensive study on 2D, 3D and solid tumor environment to explore a multifunctional biogenic nanoconjugate

Emergence of nanotechnology created a drastic change in the field of cancer therapy due to their unique features in drug delivery and imaging. Polysaccharide based nanoparticles have received extensive attention in recent years as promising nanoparticle mediated drug delivery systems. Polysaccharides are endorsed with versatile merits including high drug encapsulation efficiency, efficient drug protection against chemical or enzymatic degradation, unique ability to create a controlled release and cellular internalization. In the current study, we have fabricated doxorubicin-loaded carboxymethylated PST001 coated iron oxide nanoparticles (DOX@CM-PST-IONPs) for better management of cancer. CM-PST coated iron oxide nanoparticles co-encapsulated with chemotherapeutic drug doxorubicin, can be utilized for targeted drug delivery. Biocompatible and non-toxic nanoconjugates was found to be effective in both 2-D and 3-D cell culture system with efficient cancer cell internalization. The bench-marked potential of CM-PIONPs to produce reactive oxygen species makes it a noticeable drug delivery system to compact neoplasia. These nanoconjugates can lay concrete on a better way for the elimination of cancer spheroids and tumor burden.

Self-Assembling pH-Responsive Nanoparticle Platform Based on Pectin-Doxorubicin Conjugates for Codelivery of Anticancer Drugs.

Pharmaceutical science based on biological nanotechnology is developing rapidly in parallel with the development of nanomaterials and nanotechnology in general. Pectin is a natural polysaccharide obtainable from a wide range of sources. Here, we show that doxorubicin (DOX)-conjugated hydrophilic pectin (PET) comprising an amphiphilic polymer loaded with hydrophobic dihydroartemisinin (DHA) self-assemble into nanoparticles. Importantly, conjugated DOX and DHA could be released quickly in a weakly acidic environment by cleavage of the acid-sensitive acyl hydrazone bond. Confocal microscopy and flow cytometry confirmed that these PET-DOX/DHA nanoparticles efficiently delivered DOX into the nuclei of MCF-7 cells. Significant tumor growth reduction was monitored in a female C57BL/6 mouse model, showing that the PET-DOX/DHA nanoparticle-mediated drug delivery system inhibited tumor growth and may improve therapy. Thus, we have demonstrated that pectin may be useful in the design of materials for biomedical applications.

Synthesis and Characterization of Clarithromycin-Graphene Oxide for Antibacterial Drug Delivery

The conventional oral formulation of the antibacterial drug clarithromycin has always been a major challenging task to overcome due to its low bioavailability, short circulation half-life, poor aqueous solubility, and acidic instability inside the stomach. Therefore, targeted drug delivery system is one of the key solutions to overcome these pharmaceutical limitations. A study was conducted to formulate and optimize the clarithromycin loading efficiency of a novel nanoparticle-mediated drug delivery system based on graphene oxide as the carrier. The clarithromycin-graphene oxide nanohybrid was synthesized using a simple, non-covalent functionalization method and characterized by ultraviolet-visible and Fourier transform infrared spectroscopies. The drug loading efficiency of graphene oxide was estimated to be around 56.0 wt% and the Fourier transform infrared spectra suggested that clarithromycin was successfully conjugated onto graphene oxide as evidenced by the characteristic absorption peaks of both graphene oxide and clarithromycin. The findings herein strongly indicate that graphene oxide, as a multifunctional and versatile nanomaterial, can be a potential drug carrier for enhancing the pharmacokinetic profiles of poorly water-insoluble drugs like clarithromycin.&nbsp

Update on Nanoparticle-Based Drug Delivery System for Anti-inflammatory Treatment.

Nanobiotechnology plays an important role in drug delivery, and various kinds of nanoparticles have demonstrated new properties, which may provide opportunities in clinical treatment. Nanoparticle-mediated drug delivery systems have been used in anti-inflammatory therapies. Diseases, such as inflammatory bowel disease, rheumatoid arthritis, and osteoarthritis have been widely impacted by the pathogenesis of inflammation. Efficient delivery of anti-inflammatory drugs can reduce medical dosage and improve therapeutic effect. In this review, we discuss nanoparticles with potential anti-inflammatory activity, and we present a future perspective regarding the application of nanomedicine in inflammatory diseases.

A Biomimetic Drug Delivery System by Integrating Grapefruit Extracellular Vesicles and Doxorubicin-Loaded Heparin-Based Nanoparticles for Glioma Therapy.

Existing nanoparticle-mediated drug delivery systems for glioma systemic chemotherapy remain a great challenge due to poor delivery efficiency resulting from the blood brain barrier/blood-(brain tumor) barrier (BBB/BBTB) and insufficient tumor penetration. Here, we demonstrate a distinct design by patching doxorubicin-loaded heparin-based nanoparticles (DNs) onto the surface of natural grapefruit extracellular vesicles (EVs), to fabricate biomimetic EV-DNs, achieving efficient drug delivery and thus significantly enhancing antiglioma efficacy. The patching strategy allows the unprecedented 4-fold drug loading capacity compared to traditional encapsulation for EVs. The biomimetic EV-DNs are enabled to bypass BBB/BBTB and penetrate into glioma tissues by receptor-mediated transcytosis and membrane fusion, greatly promoting cellular internalization and antiproliferation ability as well as extending circulation time. We demonstrate that a high-abundance accumulation of EV-DNs can be detected at glioma tissues, enabling the maximal brain tumor uptake of EV-DNs and great antiglioma efficacy in vivo.

Overcoming the Blood-Brain Barrier: Successes and Challenges inDeveloping Nanoparticle-Mediated Drug Delivery Systems for the Treatment of Brain Tumours.

High-grade gliomas are still characterized by a poor prognosis, despite recent advances in surgical treatment. Chemotherapy is currently practiced after surgery, but its efficacy is limited by aspecific toxicity on healthy cells, tumour cell chemoresistance, poor selectivity, and especially by the blood–brain barrier (BBB). Thus, despite the large number of potential drug candidates, the choice of effective chemotherapeutics is still limited to few compounds. Malignant gliomas are characterized by high infiltration and neovascularization, and leaky BBB (the so-called blood–brain tumour barrier); surgical resection is often incomplete, leaving residual cells that are able to migrate and proliferate. Nanocarriers can favour delivery of chemotherapeutics to brain tumours owing to different strategies, including chemical stabilization of the drug in the bloodstream; passive targeting (because of the leaky vascularization at the tumour site); inhibition of drug efflux mechanisms in endothelial and cancer cells; and active targeting by exploiting carriers and receptors overexpressed at the blood–brain tumour barrier. Within this concern, a suitable nanomedicine-based therapy for gliomas should not be limited to cytotoxic agents, but also target the most important pathogenetic mechanisms, including cell differentiation pathways and angiogenesis. Moreover, the combinatorial approach of cell therapy plus nanomedicine strategies can open new therapeutical opportunities. The major part of attempted preclinical approaches on animal models involves active targeting with protein ligands, but, despite encouraging results, a few number of nanomedicines reached clinical trials, and most of them include drug-loaded nanocarriers free of targeting ligands, also because of safety and scalability concerns.

Current Treatment Strategies and Nanoparticle-Mediated Drug Delivery Systems for Pulmonary Arterial Hypertension.

There are three critical pathways for the pathogenesis and progression of pulmonary arterial hypertension (PAH): the prostacyclin (prostaglandin I2) (PGI2), nitric oxide (NO), and endothelin pathways. The current approved drugs targeting these three pathways, including prostacyclin (PGI2), phosphodiesterase type-5 (PDE5) inhibitors, and endothelin receptor antagonists (ERAs), have been shown to be effective, however, PAH remains a severe clinical condition and the long-term survival of patients with PAH is still suboptimal. The full therapeutic abilities of available drugs are reduced by medication, patient non-compliance, and side effects. Nanoparticles are expected to address these problems by providing a novel drug delivery approach for the treatment of PAH. Drug-loaded nanoparticles for local delivery can optimize the efficacy and minimize the adverse effects of drugs. Prostacyclin (PGI2) analogue, PDE5 inhibitors, ERA, pitavastatin, imatinib, rapamycin, fasudil, and oligonucleotides-loaded nanoparticles have been reported to be effective in animal PAH models and in vitro studies. However, the efficacy and safety of nanoparticle mediated-drug delivery systems for PAH treatment in humans are unknown and further clinical studies are required to clarify these points.

Biochemical estimation of Moringa oleifera leaf extract for synthesis of silver nanoparticle mediated drug delivery system

Breast tissue remodeling occurs throughout a women’s life from pre-menstrual to post menopausal time, hence there is a high risk of DNA damage. Estrogen metabolite generates free radical that causes DNA damage leading to cancer cell formation. Moringa oleifera leaf extract contain rich amount of Polyphenolic and Flavonoids compound which trap the free radical and thereby prevent cancer cell progression. Moreover anti-gonadotrophic hormonal activity of the leaf extract slows down the proliferation rate of T47D cell line. Hence our aim of study mainly focused to develop an anticancer drug delivery system using M. oleifera leaf extract. Silver nanoparticle (AgNp) is formed by green synthesis method using M. oleifera leaf extract. Reducing sugar, Flavonoids, Polyphenolic compound, and NADPH dependent dehydrogenase present in M. oleifera leaf extract are responsible for reduction of the silver ion (Ag+) followed by formation of metallic silver (Ag0). The formation of spherical and rectangular shaped AgNp with average size of 50 nm is reflected with sharp SPR band near 420 nm and from SEM, TEM analysis. The nanoparticle mediated polyvinyl alcohol composite film (nano-rod) is prepared for delivery of the purified anti-neoplastic phyto-compound from leaf extract. The large surface area of AgNp permits its coordination with purified compound molecule by metal ligand bonding. Therefore it provide duel effect, it acts as carrier molecule for phyto-compound and also creates cytotoxicity effect on cancer cells. Single dose treatment on HeLa cell indicates that the composite film is more effective in killing the cancer cell than the purified anti-neoplastic phyto-compound.

Argpyrimidine-tagged rutin-encapsulated biocompatible (ethylene glycol dimers) nanoparticles: Application for targeted drug delivery in experimental diabetes (Part 2)

Diabetes mellitus is characterized by hyperglycemia and associated complications. However, long-term diabetes control is not often sustained by currently available therapeutic approaches. Research on nanoparticle-mediated drug delivery systems is in progress. Here we have tested a ligand (argpyrimidine)-tagged drug (rutin)-encapsulated biocompatible (ethylene glycol dimers) nanoparticle for targeted drug delivery in streptozotocin-induced diabetic rats. Argpyrimidine, being an advanced glycation end product (AGE), directs the nanoparticles to interact with cell surface receptors of AGEs (RAGE) and delivers the drug into the cells. The bioflavonoid rutin possesses antihyperglycemic property, and has been used for nanocapsulation. Two doses of nanoparticles containing 20mg rutin/kg body weight were administered (i.v. at 7days interval) into streptozotocin-induced diabetic rats. Compared to free rutin, nanoparticle treatment appears to be significantly more effective in controlling the diabetogenic effects – hyperglycemia, hyperlipidemia, oxidative stress etc, including heart-associated complications. This approach may thus be explored for drug delivery in the treatment of diabetes mellitus.

Nanoparticle-Mediated Drug Delivery System for Pulmonary Arterial Hypertension.

Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost) -incorporated nanoparticles and imatinib (a PDGF-receptor tyrosine kinase inhibitor) -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of pulmonary arterial hypertension (PAH) and in human PAH-pulmonary arterial smooth muscle cells have been reported. The use of inhaled drug-incorporated nanoparticles might be a novel approach for the treatment of PAH.

Anti-inflammatory Nanoparticle for Prevention of Atherosclerotic Vascular Diseases.

Recent technical innovation has enabled chemical modifications of small materials and various kinds of nanoparticles have been created. In clinical settings, nanoparticle-mediated drug delivery systems have been used in the field of cancer care to deliver therapeutic agents specifically to cancer tissues and to enhance the efficacy of drugs by gradually releasing their contents. In addition, nanotechnology has enabled the visualization of various molecular processes by targeting proteinases or inflammation. Nanoparticles that consist of poly (lactic-co-glycolic) acid (PLGA) deliver therapeutic agents to monocytes/macrophages and function as anti-inflammatory nanoparticles in combination with statins, angiotensin receptor antagonists, or agonists of peroxisome proliferator-activated receptor-γ (PPARγ). PLGA nanoparticle-mediated delivery of pitavastatin has been shown to prevent inflammation and ameliorated features associated with plaque ruptures in hyperlipidemic mice. PLGA nanoparticles were also delivered to tissues with increased vascular permeability and nanoparticles incorporating pitavastatin, injected intramuscularly, were retained in ischemic tissues and induced therapeutic arteriogenesis. This resulted in attenuation of hind limb ischemia. Ex vivo treatment of vein grafts with imatinib nanoparticles before graft implantation has been demonstrated to inhibit lesion development. These results suggest that nanoparticle-mediated drug delivery system can be a promising strategy as a next generation therapy for atherosclerotic vascular diseases.

Fabrication of a pH responsive DOX conjugated PEGylated palladium nanoparticle mediated drug delivery system: an in vitro and in vivo evaluation

Schematic illustration of the possible mechanism of pH based drug delivery system of DOX conjugated PEGylated PdNPs induced apoptosis in HeLa cells.

冠動脈疾患に対するナノ粒子・ドラッグデリバリーシステムの開発

冠動脈疾患に対するナノ粒子・ドラッグデリバリーシステムの開発