Nano-based Drug Delivery Systems Research Articles

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.

Folate receptor-targeted indomethacin-loaded gold nanoparticles enhance drug chemotherapeutic efficacy in glioblastoma cells and spheroids

Glioblastoma is a highly malignant brain cancer with a poor survival rate. Increasing evidence demonstrates the anticancer activity, including anti-glioma activity, of indomethacin (IND), a non-steroidal anti-inflammatory drug. However, due to the IND's poor aqueous solubility, nano-based drug delivery systems, especially gold nanoparticles (AuNPs), are great tools for increasing solubility and therapeutic efficacy. Herein, glutathione (GSH)-coated folic acid (FA)-modified AuNPs were used for the first time to generate IND-loaded AuNPs (55 nm), which were successfully synthesized according to DLS, TEM, FTIR, NMR, and TGA results. IND/AuNPs were found to have spherical morphology, nanoscale particle size, narrow size distribution, and good stability. Fluorescence and confocal imaging demonstrated that the nanoparticles penetrated folate receptor (FR)+ U-87MG human glioblastoma monolayer and sphere-forming cells. Remarkably, short-term exposure (4h) to IND/AuNPs significantly increased IND cytotoxicity in U-87MG cells after post-44h and -68h (>35- and >120-fold, respectively). Even against prolonged exposure of cells to IND for 24h, 48h, and 72h, IND/AuNP treatment revealed a marked result: glioma proliferation slowed by 7.38-fold, 6.8-fold, and 17-fold, respectively. No significant effect was observed on the FR− cell lines. The increased antitumoral activity was accompanied by efficient increased apoptosis in glioblastoma cells due to the IND/AuNP treatments. Moreover, compared to free-drug and control groups, IND/AuNP treatments markedly reduced glioblastoma growth in 3D spheroids (in vitro system that mimics in vivo tumors). Therefore, these findings suggest that the new spherical IND/Au-GSH-FA NP conjugate has the potential to be a beneficial therapeutic agent in glioblastoma therapy by targeting FRs.

Research advances on signaling pathways regulating the polarization of tumor-associated macrophages in lung cancer microenvironment.

Lung cancer (LC) is one of the most common cancer worldwide. Tumor-associated macrophages (TAMs) are important component of the tumor microenvironment (TME) and are closely related to the stages of tumor occurrence, development, and metastasis. Macrophages are plastic and can differentiate into different phenotypes and functions under the influence of different signaling pathways in TME. The classically activated (M1-like) and alternatively activated (M2-like) represent the two polarization states of macrophages. M1 macrophages exhibit anti-tumor functions, while M2 macrophages are considered to support tumor cell survival and metastasis. Macrophage polarization involves complex signaling pathways, and blocking or regulating these signaling pathways to enhance macrophages' anti-tumor effects has become a research hotspot in recent years. At the same time, there have been new discoveries regarding the modulation of TAMs towards an anti-tumor phenotype by synthetic and natural drug components. Nanotechnology can better achieve combination therapy and targeted delivery of drugs, maximizing the efficacy of the drugs while minimizing side effects. Up to now, nanomedicines targeting the delivery of various active substances for reprogramming TAMs have made significant progress. In this review, we primarily provided a comprehensive overview of the signaling crosstalk between TAMs and various cells in the LC microenvironment. Additionally, the latest advancements in novel drugs and nano-based drug delivery systems (NDDSs) that target macrophages were also reviewed. Finally, we discussed the prospects of macrophages as therapeutic targets and the barriers to clinical translation.

Nano-based drug delivery systems for active ingredients from traditional Chinese medicine: Harnessing the power of nanotechnology.

Introduction: Traditional Chinese medicine (TCM) is gaining worldwide popularity as a complementary and alternative medicine. The isolation and characterization of active ingredients from TCM has become optional strategies for drug development. In order to overcome the inherent limitations of these natural products such as poor water solubility and low bioavailability, the combination of nanotechnology with TCM has been explored. Taking advantage of the benefits offered by the nanoscale, various drug delivery systems have been designed to enhance the efficacy of TCM in the treatment and prevention of diseases. Methods: The manuscript aims to present years of research dedicated to the application of nanotechnology in the field of TCM. Results: The manuscript discusses the formulation, characteristics and therapeutic effects of nano-TCM. Additionally, the formation of carrier-free nanomedicines through self-assembly between active ingredients of TCM is summarized. Finally, the paper discusses the safety behind the application of nano-TCM and proposes potential research directions. Discussion: Despite some achievements, the safety of nano-TCM still need special attention. Furthermore, exploring the substance basis of TCM formulas from the perspective of nanotechnology may provide direction for elucidating the scientific intension of TCM formulas.

A Review of Recent Developments in Biopolymer Nano-Based Drug Delivery Systems with Antioxidative Properties: Insights into the Last Five Years.

In recent years, biopolymer-based nano-drug delivery systems with antioxidative properties have gained significant attention in the field of pharmaceutical research. These systems offer promising strategies for targeted and controlled drug delivery while also providing antioxidant effects that can mitigate oxidative stress-related diseases. Generally, the healthcare landscape is constantly evolving, necessitating the continual development of innovative therapeutic approaches and drug delivery systems (DDSs). DDSs play a pivotal role in enhancing treatment efficacy, minimizing adverse effects, and optimizing patient compliance. Among these, nanotechnology-driven delivery approaches have garnered significant attention due to their unique properties, such as improved solubility, controlled release, and targeted delivery. Nanomaterials, including nanoparticles, nanocapsules, nanotubes, etc., offer versatile platforms for drug delivery and tissue engineering applications. Additionally, biopolymer-based DDSs hold immense promise, leveraging natural or synthetic biopolymers to encapsulate drugs and enable targeted and controlled release. These systems offer numerous advantages, including biocompatibility, biodegradability, and low immunogenicity. The utilization of polysaccharides, polynucleotides, proteins, and polyesters as biopolymer matrices further enhances the versatility and applicability of DDSs. Moreover, substances with antioxidative properties have emerged as key players in combating oxidative stress-related diseases, offering protection against cellular damage and chronic illnesses. The development of biopolymer-based nanoformulations with antioxidative properties represents a burgeoning research area, with a substantial increase in publications in recent years. This review provides a comprehensive overview of the recent developments within this area over the past five years. It discusses various biopolymer materials, fabrication techniques, stabilizers, factors influencing degradation, and drug release. Additionally, it highlights emerging trends, challenges, and prospects in this rapidly evolving field.

Chitosan mediated smart photodynamic therapy based novel drug delivery systems- a futuristic view

In order to improve the pharmacological and therapeutic properties of drugs, researchers have attempted numerous novel approaches, such as stimuli-responsive systems, and targeted drug delivery systems. These systems can be attempted by nano-based drug delivery systems involving biocompatible polymers. One among which is chitosan, a linear polysaccharide, a promising potential polymer that gained interest in delivering challenging drugs. Chitosan can encapsulate and release the drugs in a controlled/sustained manner. Chitosan can be used to develop a variety of drug delivery carriers, including films, gels, nanoparticles, nanodispersions, nanomicelles, and patches. In this regimen, minimally invasive photodynamic therapy has recently gained much interest in treating vascular diseases, including cancer, ocular diseases, microbial infections, skin disorders, etc. Photodynamic therapy utilizes light excited at a specific wavelength, eliciting singlet oxygen production. Self-lighting photodynamic therapy and combination-based photodynamic therapy also offer synergistic effects. Photodynamic therapy is more selective and specific, which may offer treatment for deep-seated diseased tissues compared to conventional therapeutic modalities. Light-activated novel drug delivery formulations have been reported using various biocompatible polymers, including chitosan. Chitosan offers its effectiveness as mucoadhesiveness, tissue penetrability, antioxidant, antimicrobial properties, supports in singlet oxygen generation, and shown its benefits in photodynamic therapy. Therefore, this review presents numerous applications of chitosan-based light-activated drug delivery systems with particular emphasis on their patents and clinical trials. The literature has been collected and compiled using various search resources such as Science Direct, J-Gate, Google Scholar, PubMed, and research data.

Nanoparticle-Mediated Synergistic Chemoimmunotherapy for Cancer Treatment.

Until now, there has been a lack of effective strategies for cancer treatment. Immunotherapy has high potential in treating several cancers but its efficacy is limited as a monotherapy. Chemoimmunotherapy (CIT) holds promise to be widely used in cancer treatment. Therefore, identifying their involvement and potential synergy in CIT approaches is decisive. Nano-based drug delivery systems (NDDSs) are ideal delivery systems because they can simultaneously target immune cells and cancer cells, promoting drug accumulation, and reducing the toxicity of the drug. In this review, we first introduce five current immunotherapies, including immune checkpoint blocking (ICB), adoptive cell transfer therapy (ACT), cancer vaccines, oncolytic virus therapy (OVT) and cytokine therapy. Subsequently, the immunomodulatory effects of chemotherapy by inducing immunogenic cell death (ICD), promoting tumor killer cell infiltration, down-regulating immunosuppressive cells, and inhibiting immune checkpoints have been described. Finally, the NDDSs-mediated collaborative drug delivery systems have been introduced in detail, and the development of NDDSs-mediated CIT nanoparticles has been prospected.

A holistic review of recent advances in nano-based drug delivery systems for the treatment of triple-negative breast cancer (TNBC)

A holistic review of recent advances in nano-based drug delivery systems for the treatment of triple-negative breast cancer (TNBC)

Self-assembled nanoparticle-mediated cascade chemotherapy and chemodynamic therapy for enhanced tumor therapy

Chemodynamic therapy (CDT) is a non-invasive treatment strategy that aims to combat tumor growth by efficiently generating reactive oxygen species (ROS). However, the effectiveness of CDT can be limited by factors such as the availability of endogenous hydrogen peroxide (H2O2). Here, we established an intelligent nano-based drug delivery system responsive to the tumor microenvironment by self-assembling Cu2+, cisplatin, and L-histidine to form nanoparticles (Pt/CuH NPs), which can achieve the therapeutic effect of specific tumor killing by cascading chemotherapy with CDT. The Pt/CuH NPs are triggered by the acidic conditions and high glutathione (GSH) levels present in the tumor microenvironment, leading to the release of cisplatin and Cu2+. Cisplatin facilitates the production of H2O2 through a two-step enzymatic reaction, subsequently triggering ROS cascade that is amplified by CDT. Concurrently, Cu2+ consumes GSH and is reduced to Cu+, which reacts with H2O2 in an efficient Fenton-like reaction, amplifying oxidative stress and ultimately enhancing the anti-tumor therapeutic efficacy. Pt/CuH NPs demonstrated a significant cytotoxic effect on tumor cells in vitro. In vivo studies in mice indicated minimal toxic side effects at the tested dosages. The Pt/CuH NPs effectively combine chemotherapy and CDT strategies, showcasing the potential of a chemotherapy-cascading CDT approach for anti-tumor treatment.

Polydopamine-Mediated Metal-Organic Frameworks Modification for Improved Biocompatibility.

Engineered nanomaterials are promising in biomedical application. However, insufficient understanding of their biocompatibility at the cellular and organic levels prevents their widely biomedical applications. Metal-organic frameworks (MOFs) have attracted increasing attention in recent years. In this work, zeolitic imidazolate framework-8 (ZIF-8) and polydopamine (PDA)-modified ZIF-8 are chosen as model nanomaterials due to its emergent role in nanomedicine. In vitro, the results demonstrate that the PDA coating greatly alleviates the cytotoxicity of ZIF-8 to RAW264.7, LO2, and HST6, which represent three different cell types in liver organs. Mechanistically, ZIF-8 entering into the cells can greatly induce the reactive oxygen species generation, which subsequently induces cell cycle delay and autophagy, ultimately leads to enhanced cytotoxicity. Further, human umbilical vein endothelial cells model and zebrafish embryos assay also confirm that PDA can compromise the ZIF-8 toxicity significantly. This study reveals that PDA-coated MOFs nanomaterials show great potential in nano-based drug delivery systems .

Cationic anticancer peptide L-K6-modified and doxorubicin-loaded mesoporous silica nanoparticles reverse multidrug resistance of breast cancer

Multidrug resistance (MDR) is the major challenge for chemotherapy of cancer and makes the treatment benefits unsustainable. To overcome this issue, nanotechnology has been introduced and various nanocarriers have been constructed to reverse MDR in drug resistant cancer cells. Here, mesoporous silica nanoparticle (MSN-COOH) were modified with cationic anticancer peptide L-K6 (MSN@L-K6), and further loaded with doxorubicin (DOX) to construct an anticancer nano-system, MSN@L-K6@DOX. Our results showed that MSN@L-K6@DOX released DOX in pH-sensitive manner, which enable to be highly efficient in delivering drugs to tumors, counterbalancing the MDR. In addition, MSN@L-K6@DOX treatment decreased the expression level of P-glycoprotein in MCF-7/ADR cells, enhanced the intracellular accumulation of DOX, and thereafter reversed the MDR of MCF-7/ADR cells to DOX. Moreover, the MDR reversal activity of MSN@L-K6@DOX was further confirmed in xenograft mouse model, as evidenced by the decreased tumor volume and weight. These results indicate the MDR reversal activity of MSN@L-K6@DOX and may provide a novel strategy for the development of nano-based drug delivery system to overcome cancer MDR.

Pathophysiological aspects of transferrin-A potential nano-based drug delivery signaling molecule in therapeutic target for varied diseases.

Transferrin (Tf), widely known for its role as an iron-binding protein, exemplifies multitasking in biological processes. The role of Tf in iron metabolism involves both the uptake of iron from Tf by various cells, as well as the endocytosis mediated by the complex of Tf and the transferrin receptor (TfR). The direct conjugation of the therapeutic compound and immunotoxin studies using Tf peptide or anti-Tf receptor antibodies as targeting moieties aims to prolong drug circulation time and augment efficient cellular drug uptake, diminish systemic toxicity, traverse the blood-brain barrier, restrict systemic exposure, overcome multidrug resistance, and enhance therapeutic efficacy with disease specificity. This review primarily discusses the various biological actions of Tf, as well as the development of Tf-targeted nano-based drug delivery systems. The goal is to establish the use of Tf as a disease-targeting component, accentuating the potential therapeutic applications of this protein.

Benefits and Pitfalls of a Glycosylation Inhibitor Tunicamycin in the Therapeutic Implication of Cancers.

The aberrant glycosylation is a hallmark of cancer progression and chemoresistance. It is also an immune therapeutic target for various cancers. Tunicamycin (TM) is one of the potent nucleoside antibiotics and an inhibitor of aberrant glycosylation in various cancer cells, including breast cancer, gastric cancer, and pancreatic cancer, parallel with the inhibition of cancer cell growth and progression of tumors. Like chemotherapies such as doxorubicin (DOX), 5'fluorouracil, etoposide, and cisplatin, TM induces the unfolded protein response (UPR) by blocking aberrant glycosylation. Consequently, stress is induced in the endoplasmic reticulum (ER) that promotes apoptosis. TM can thus be considered a potent antitumor drug in various cancers and may promote chemosensitivity. However, its lack of cell-type-specific cytotoxicity impedes its anticancer efficacy. In this review, we focus on recent advances in our understanding of the benefits and pitfalls of TM therapies in various cancers, including breast, colon, and pancreatic cancers, and discuss the mechanisms identified by which TM functions. Finally, we discuss the potential use of nano-based drug delivery systems to overcome non-specific toxicity and enhance the therapeutic efficacy of TM as a targeted therapy.

Key processes in tumor metastasis and therapeutic strategies with nanocarriers: a review.

Cancer metastasis is the leading cause of cancer-related death. Metastasis occurs at all stages of tumor development, with unexplored changes occurring at the primary site and distant colonization sites. The growing understanding of the metastatic process of tumor cells has contributed to the emergence of better treatment options and strategies. This review summarizes a range of features related to tumor cell metastasis and nanobased drug delivery systems for inhibiting tumor metastasis. The mechanisms of tumor metastasis in the ideal order of metastatic progression were summarized. We focus on the prominent role of nanocarriers in the treatment of tumor metastasis, summarizing the latest applications of nanocarriers in combination with drugs to target important components and processes of tumor metastasis and providing ideas for more effective nanodrug delivery systems.

Recent Development and Future Aspects: Nano-Based Drug Delivery System in Cancer Therapy

Recent Development and Future Aspects: Nano-Based Drug Delivery System in Cancer Therapy

Advances in nano-based drug delivery systems for the management of cytokine influx-mediated inflammation in lung diseases.

Asthma, lung cancer, cystic fibrosis, tuberculosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and COVID-19 are few examples of inflammatory lung conditions that cause cytokine release syndrome. It can initiate a widespread inflammatory response and may activate several inflammatory pathways that cause multiple organ failures leading to increased number of deaths and increased prevalence rates around the world. Nanotechnology-based therapeutic modalities such as nanoparticles, liposomes, nanosuspension, monoclonal antibodies, and vaccines can be used in the effective treatment of inflammatory lung diseases at both cellular and molecular levels. This would also help significantly in the reduction of patient mortality. Therefore, nanotechnology could be a potent platform for repurposing current medications in the treatment of inflammatory lung diseases. The aim and approach of this article are to highlight the clinical manifestations of cytokine storm in inflammatory lung diseases along with the advances and potential applications of nanotechnology-based therapeutics in the management of cytokine storm. Further in-depth studies are required to understand the molecular pathophysiology, and how nanotechnology-based therapeutics can help to effectively combat this problem.

Unveiling the optimal path: High-pressure homogenization and D-phase emulsification methods for borage oil nanoemulsion design

Borage oil contains high levels of essential omega-6 fatty acids, which are important for skin structure and function. For this reason, this oil can be used for the treatment of cutaneous diseases including atopic dermatitis. This disease is associated with an abnormality in essential fatty acids (EFAs) metabolism, particularly in the production of gamma-linolenic acid, leading to impaired incorporation of EFAs into the phospholipid membrane. EFAs bioavailability can be enhanced by using a borage oil nano-based drug delivery system. In this study a borage oil nanoemulsion was prepared using high-pressure homogenization (HPH) and D-phase emulsification (DPE), respectively, high and low energy methods. A design space approach was performed to optimize the formulations. The optimized HPH nanoemulsion (HPH-NE) presented a particle size and zeta potential (ZP) of 425.3 ± 5.6 nm, and − 19.4 ± 3.7 mV, respectively. For the DPE nanoemulsion (DPE-NE) the particle size was 334.4 ± 5.2 nm, and the zeta potential was − 34.6 ± 1.0 mV. Furthermore, DPE-NE presented higher toxicity compared to HPH-NE, possibly related to the presence of the polyol. These nanoemulsions may improve the borage oil bioavailability for oral administration. Thus, they can be used as an adjuvant therapy in the treatment of atopic dermatitis.

Simultaneous Light-Triggered Release of Nitric Oxide and Carbon Monoxide from a Lipid-Coated Upconversion Nanosystem Inhibits Colon Tumor Growth.

Gas therapy has gained noteworthy attention in biomedical research, with the rise of gas-releasing molecules enhancing their therapeutic potential, especially when integrated into nano-based drug delivery systems. Herein, we present a lipid-coated gas delivery system to simultaneously shuttle two gas-releasing molecules carrying nitric oxide (NO) and carbon monoxide (CO), respectively. Upconversion nanoparticles (UCNPs) are designed to generate photons at 360 nm upon 808 nm of near-infrared (NIR) irradiation. These in situ-generated UV photons trigger simultaneous NO and CO release from S-nitrosoglutathione (GSNO) and the CO-releasing molecule (CORM), respectively, which are coloaded into lipid-coated UCNP/GSNO/CORM/FA nanoparticles (LUGCF). LUGCF with a GSNO/CORM mass ratio of 2:1 is determined to be optimal in terms of synergistically instigating apoptosis in HCT116 and CT26 colon cancer cells, where both NO/CO are released and subsequent production of ROS are detected. This CO/NO combination nanoplatform exhibits a very effective inhibition of colon tumor growth in vivo at relatively low doses upon a mild 808 nm irradiation. Overall, we effectively integrated two therapeutic gas-releasing molecules in one NIR-responsive nanosystem, presenting a promising therapeutic strategy for future biomedical applications in dual-gas cancer therapy.

Nano-Based Drug Delivery Systems: Potential Developments in the Therapy of Metastatic Osteosarcoma-A Narrative Review.

Osteosarcoma, a predominant malignant bone tumor, poses significant challenges due to its high metastatic and recurrent nature. Although various therapeutic strategies are currently in use, they often inadequately target osteosarcoma metastasis. This review focuses on the potential of nanoscale drug delivery systems to bridge this clinical gap. It begins with an overview of the molecular mechanisms underlying metastatic osteosarcoma, highlighting the limitations of existing treatments. The review then transitions to an in-depth examination of nanoscale drug delivery technologies, emphasizing their potential to enhance drug bioavailability and reduce systemic toxicity. Central to this review is a discussion of recent advancements in utilizing nanotechnology for the potential intervention of metastatic osteosarcoma, with a critical analysis of several preclinical studies. This review aims to provide insights into the potential applications of nanotechnology in metastatic osteosarcoma therapy, setting the stage for future clinical breakthroughs and innovative cancer treatments.

In Silico Investigation on the Molecular Behavior and Structural Stability of the Rosette Nanotubes as the Drug Vehicles for Paclitaxel, an Anti-Cancer Drug

Most anticancer drugs affect healthy cells in addition to cancer cells, causing severe side effects. Targeted delivery by nano-based drug delivery systems (NDDS) can reduce these severe side effects while maintaining therapeutic efficacy. This work introduced rosette nanotube (RNT) as a potential drug vehicle for paclitaxel (PTX) due to its self-assembling property, biocompatibility, amphiphilicity, and low toxicity. Molecular dynamics (MD) simulations aided with molecular mechanics Poisson Boltzmann surface area (MMPBSA) analysis are used here to investigate the molecular behavior and the loading energetics of each type of RNT (K1, xK1, and iEt-xK1) with PTX. Analysis showed that the most probable configuration of PTX is on either end of each RNT. The binding free energies (−117.74 to −69.29 kJ/mol) when PTX is closer to one end were stronger than when it is in the inner channel (−53.51 to −40.88 kJ/mol). The latter alludes to the encapsulation of the PTX by each RNT. Thus, loading is possible by encapsulation during the self-assembly process given the favorable estimated binding free energies. Based on the results, RNT has potential as a drug vehicle for PTX, which warrants further investigation.