Nanoparticulate Drug Delivery Systems Research Articles

Progress of nanoparticle drug delivery system for the treatment of glioma.

Gliomas are typical malignant brain tumours affecting a wide population worldwide. Operation, as the common treatment for gliomas, is always accompanied by postoperative drug chemotherapy, but cannot cure patients. The main challenges are chemotherapeutic drugs have low blood-brain barrier passage rate and a lot of serious adverse effects, meanwhile, they have difficulty targeting glioma issues. Nowadays, the emergence of nanoparticles (NPs) drug delivery systems (NDDS) has provided a new promising approach for the treatment of gliomas owing to their excellent biodegradability, high stability, good biocompatibility, low toxicity, and minimal adverse effects. Herein, we reviewed the types and delivery mechanisms of NPs currently used in gliomas, including passive and active brain targeting drug delivery. In particular, we primarily focused on various hopeful types of NPs (such as liposome, chitosan, ferritin, graphene oxide, silica nanoparticle, nanogel, neutrophil, and adeno-associated virus), and discussed their advantages, disadvantages, and progress in preclinical trials. Moreover, we outlined the clinical trials of NPs applied in gliomas. According to this review, we provide an outlook of the prospects of NDDS for treating gliomas and summarise some methods that can enhance the targeting specificity and safety of NPs, like surface modification and conjugating ligands and peptides. Although there are still some limitations of these NPs, NDDS will offer the potential for curing glioma patients.

Dual-targeted nanoparticulate drug delivery systems for enhancing triple-negative breast cancer treatment

The efficacy of DNA-damaging agents, such as the topoisomerase I inhibitor SN38, is often compromised by the robust DNA repair mechanisms in tumor cells, notably homologous recombination (HR) repair. Addressing this challenge, we introduce a novel nano-strategy utilizing binary tumor-killing mechanisms to enhance the therapeutic impact of DNA damage and mitochondrial dysfunction in cancer treatment. Our approach employs a synergistic drug pair comprising SN38 and the BET inhibitor JQ-1. We synthesized two prodrugs by conjugating linoleic acid (LA) to SN38 and JQ-1 via a cinnamaldehyde thioacetal (CT) bond, facilitating co-delivery. These prodrugs co-assemble into a nanostructure, referred to as SJNP, in an optimal synergistic ratio. SJNP was validated for its efficacy at both the cellular and tissue levels, where it primarily disrupts the transcription factor protein BRD4. This disruption leads to downregulation of BRCA1 and RAD51, impairing the HR process and exacerbating DNA damage. Additionally, SJNP releases cinnamaldehyde (CA) upon CT linkage cleavage, elevating intracellular ROS levels in a self-amplifying manner and inducing ROS-mediated mitochondrial dysfunction. Our results indicate that SJNP effectively targets murine triple-negative breast cancer (TNBC) with minimal adverse toxicity, showcasing its potential as a formidable opponent in the fight against cancer.

MMPs/pH synergically responsive XTS-Prussian blue nanoparticles inhibiting proliferation and migration of RAFLS assisted with laser irradiation

Rheumatoid arthritis(RA) is a condition in which the joints are in a weakly acidic environment. In RA, RA fibroblastlike synoviocytes( RAFLS) in the joints become abnormally activated and secrete a large amount of matrix metalloproteinases(MMPs), and the receptor protein CD44 on the cell membrane is specifically upregulated. Xuetongsu(XTS), an active ingredient in the Tujia ethnomedicine Xuetong, is known to inhibit the proliferation of RAFLS. However, its development and utilization have been limited due to poor targeting ability. A biomimetic XTS-Prussian blue nanoparticles(PB NPs) drug delivery system called THMPX NPs which can target CD44 was constructed in this study. The surface of THMPX NPs was modified with hyaluronic acid(HA) and a long chain of triglycerol monostearate(TGMS) and 3-aminobenzeneboronic acid(PBA)(PBA-TGMS). The overexpressed MMPs and H+ in inflammatory RAFLS can synergistically cleave the PBA-TGMS on the surface of the nanoparticles, exposing HA to interact with CD44. This allows THMPX NPs to accumulate highly in RAFLS, and upon near-infrared light irradiation, generate heat and release XTS, thereby inhibiting the proliferation and migration of RAFLS. Characterization revealed that THMPX NPs were uniform cubes with a diameter of(190. 3±4. 7) nm and an average potential of(-15. 3± 2. 3) m V. Upon near-infrared light irradiation for 5 min, the temperature of THMPX NPs reached 41. 5 ℃, indicating MMPs and H+-triggered drug release. Safety assessments showed that THMPX NPs had a hemolysis rate of less than 4% and exhibited no cytotoxicity against normal RAW264. 7 and human fibroblast-like synoviocytes(HFLS). In vitro uptake experiments demonstrated the significant targeting ability of THMPX NPs to RAFLS. Free radical scavenging experiments revealed excellent free radical clearance capacity of THMPX NPs, capable of removing reactive oxygen species in RAFLS. Cell counting kit-8 and scratch assays demonstrated that THMPX NPs significantly suppressed the viability and migratory ability of RAFLS. This study provides insights into the development of innovative nanoscale targeted drugs from traditional ethnic medicines for RA treatment.

Leading Paediatric Infectious Diseases-Current Trends, Gaps, and Future Prospects in Oral Pharmacotherapeutic Interventions.

Paediatric infectious diseases contribute significantly to global health challenges. Conventional therapeutic interventions are not always suitable for children, as they are regularly accompanied with long-standing disadvantages that negatively impact efficacy, thus necessitating the need for effective and child-friendly pharmacotherapeutic interventions. Recent advancements in drug delivery technologies, particularly oral formulations, have shown tremendous progress in enhancing the effectiveness of paediatric medicines. Generally, these delivery methods target, and address challenges associated with palatability, dosing accuracy, stability, bioavailability, patient compliance, and caregiver convenience, which are important factors that can influence successful treatment outcomes in children. Some of the emerging trends include moving away from creating liquid delivery systems to developing oral solid formulations, with the most explored being orodispersible tablets, multiparticulate dosage forms using film-coating technologies, and chewable drug products. Other ongoing innovations include gastro-retentive, 3D-printed, nipple-shield, milk-based, and nanoparticulate (e.g., lipid-, polymeric-based templates) drug delivery systems, possessing the potential to improve therapeutic effectiveness, age appropriateness, pharmacokinetics, and safety profiles as they relate to the paediatric population. This manuscript therefore highlights the evolving landscape of oral pharmacotherapeutic interventions for leading paediatric infectious diseases, crediting the role of innovative drug delivery technologies. By focusing on the current trends, pointing out gaps, and identifying future possibilities, this review aims to contribute towards ongoing efforts directed at improving paediatric health outcomes associated with the management of these infectious ailments through accessible and efficacious drug treatments.

On the additive artificial intelligence-based discovery of nanoparticle neurodegenerative disease drug delivery systems.

Neurodegenerative diseases are characterized by slowly progressing neuronal cell death. Conventional drug treatment strategies often fail because of poor solubility, low bioavailability, and the inability of the drugs to effectively cross the blood-brain barrier. Therefore, the development of new neurodegenerative disease drugs (NDDs) requires immediate attention. Nanoparticle (NP) systems are of increasing interest for transporting NDDs to the central nervous system. However, discovering effective nanoparticle neuronal disease drug delivery systems (N2D3Ss) is challenging because of the vast number of combinations of NP and NDD compounds, as well as the various assays involved. Artificial intelligence/machine learning (AI/ML) algorithms have the potential to accelerate this process by predicting the most promising NDD and NP candidates for assaying. Nevertheless, the relatively limited amount of reported data on N2D3S activity compared to assayed NDDs makes AI/ML analysis challenging. In this work, the IFPTML technique, which combines information fusion (IF), perturbation theory (PT), and machine learning (ML), was employed to address this challenge. Initially, we conducted the fusion into a unified dataset comprising 4403 NDD assays from ChEMBL and 260 NP cytotoxicity assays from journal articles. Through a resampling process, three new working datasets were generated, each containing 500,000 cases. We utilized linear discriminant analysis (LDA) along with artificial neural network (ANN) algorithms, such as multilayer perceptron (MLP) and deep learning networks (DLN), to construct linear and non-linear IFPTML models. The IFPTML-LDA models exhibited sensitivity (Sn) and specificity (Sp) values in the range of 70% to 73% (>375,000 training cases) and 70% to 80% (>125,000 validation cases), respectively. In contrast, the IFPTML-MLP and IFPTML-DLN achieved Sn and Sp values in the range of 85% to 86% for both training and validation series. Additionally, IFPTML-ANN models showed an area under the receiver operating curve (AUROC) of approximately 0.93 to 0.95. These results indicate that the IFPTML models could serve as valuable tools in the design of drug delivery systems for neurosciences.

Charge-Switchable nanoparticles to enhance tumor penetration and accumulation

Nanoparticle-based drug delivery systems hold potential in chemotherapy, but their limited accumulation in tumor tissues hinders effective drug concentration for combating tumor growth. Hence, altering the physicochemical properties of nanoparticles, particularly their surface charge, can enhance their performance. This study utilized a computational model to explore a nanoparticle drug delivery system capable of dynamically adjusting its surface charge. In the model, nanoparticles in the bloodstream were assigned a neutral or positive charge, which, upon reaching the tumor microenvironment, switched to a neutral or negative charge, and releasing chemotherapy drugs into the extracellular space. Results revealed that circulating nanoparticles with a positive surface charge, despite having a shorter circulation and high clearance rate compared to their neutral counterparts, could accumulate significantly in the tissue due to their high transvascular rate. After extravasation, neutralized surface-charged nanoparticles tended to accumulate only near blood microvessels due to their low diffusion rate, resulting in substantial released drug drainage back into the bloodstream. On the other hand, nanoparticles with a negative surface charge in the tumor’s extracellular space, due to the reduction of nano-bio interactions, were able to penetrate deeper into the tumor, and increasing drug bioavailability by reducing the volume of drained drugs. Furthermore, the analysis suggested that burst drug release yields a higher drug concentration than sustained drug release, however their creation of bioavailability dependent on nanoparticle accumulation in the tissue. The study’s findings demonstrate the potential of this delivery system and offer valuable insights for future research in this area.

From Traditional Medicine to Advanced Therapeutics: The Renaissance of Phyto-nano Interventions in Psoriasis.

Psoriasis is an autoimmune systemic chronic inflammatory disease that exhibits characteristic detrimental effects on the skin, often leading to infections or comorbid conditions. The multifaceted nature of psoriasis has made it very challenging to treat, especially with current chemotherapy options. Therefore, it is essential to consider phytoconstituents as novel alternatives. However, despite demonstrating higher anti-inflammatory, anti-psoriasis, and immunomodulatory potential, their clinical usage is hindered due to their poor physicochemical properties. To address these drawbacks, nanoparticulate drug delivery systems have been developed, helping to achieve better permeation of phytoconstituents through topical administration. This has breathed new life into traditional systems of medicine, particularly in the context of treating psoriasis. In this current review, we present a detailed, comprehensive, and up-to-date analysis of the literature, which will contribute to affirming the clinical role of phyto-nano interventions against psoriasis.

Folate functionalized multifunctional CuO@PHBV@PDA nanoplatform for pH-Responsive dual drug delivery and ROS-driven apoptosis in breast cancer

Current anticancer nanocarriers are still constrained by a disparity between their various functionalities and biocompatibility. Drug combinations delivered via cell-specific nanocarriers have the potential to improve therapeutic efficacy. Herein, we prepared a ROS-responsive CuO nanoparticle drug delivery system for treating breast cancer loaded with 5-Fluorouracil (5-FU) and paclitaxel (PTX), encased in a layer of PHBV/PDA and embellished with folate to yield 5-FU@PTX-CuO@PHBV@PDA/FA NPs. Excellent monodispersity, size stability, and biocompatibility were displayed by the resulting nanoplatform with a diameter of about 186.3 ± 7.2 nm. Synthesized nanoplatform was studied in NIH 3T3 and MCF-7 cells to determine their antitumor mechanism. Invitro pH-dependent drug release rate, drug encapsulation, loading efficiency, and hemocompatibility were all quantified via Ultraviolet–visible spectroscopy. Half-maximal inhibitory concentration values for dual drug-loaded CuO@PHBV@PDA/FA NPs and free drugs combination were 12.5 and 25 μg/mL, respectively, indicating considerably stronger antitumor activity of 5-FU@PTX-CuO@PHBV@PDA/FA NPs than free drugs combination. Apoptotic cell death, mitochondrial membrane potential loss, and ROS production were also examined in vitro. In contrary, dual drug-loaded nanoparticles exhibited concentration-dependent and synergistic cytotoxicity towards MCF-7 cells. Together, these findings suggest that the 5-FU@PTX-CuO@PHBV@PDA/FA nanoplatform may help to resolve the conflict between the multifunctionality and biocompatibility of nanocarriers.

Cryo-Milled β-Glucan Nanoparticles for Oral Drug Delivery.

Gemcitabine is a nucleoside analog effective against a number of cancers. However, it has an oral bioavailability of less than 10%, due to its high hydrophilicity and low permeability through the intestinal epithelium. Therefore, the aim of this project was to develop a novel nanoparticulate drug delivery system for the oral delivery of gemcitabine to improve its oral bioavailability. In this study, gemcitabine-loaded β-glucan NPs were fabricated using a film-casting method followed by a freezer-milling technique. As a result, the NPs showed a small particle size of 447.6 ± 14.2 nm, and a high drug entrapment efficiency of 64.3 ± 2.1%. By encapsulating gemcitabine into β-glucan NPs, a sustained drug release profile was obtained, and the anomalous diffusion release mechanism was analyzed, indicating that the drug release was governed by diffusion through the NP matrix as well as matrix erosion. The drug-loaded NPs had a greater ex vivo drug permeation through the porcine intestinal epithelial membrane compared to the plain drug solution. Cytotoxicity studies showed a safety profile of the β-glucan polymers, and the IC50s of drug solution and drug-loaded β-glucan NPs were calculated as 228.8 ± 31.2 ng·mL-1 and 306.1 ± 46.3 ng·mL-1, respectively. Additionally, the LD50 of BALB/c nude mice was determined as 204.17 mg/kg in the acute toxicity studies. Notably, pharmacokinetic studies showed that drug-loaded β-glucan NPs could achieve a 7.4-fold longer T1/2 and a 5.1-fold increase in oral bioavailability compared with plain drug solution. Finally, in vivo pharmacodynamic studies showed the promising capability of gemcitabine-loaded β-glucan NPs to inhibit the 4T1 breast tumor growth, with a 3.04- and 1.74-fold reduction compared to the untreated control and drug solution groups, respectively. In conclusion, the presented freezer-milled β-glucan NP system is a suitable drug delivery method for the oral delivery of gemcitabine and demonstrates a promising potential platform for oral chemotherapy.

Bioactive molecule-based nano-particulate drug delivery system for antifertility activity

Current research work was design to develop bioactive molecule (Plumbagin) loaded nanoparticle formulation by using Design of experiment to investigate its formulation characteristics and in-vivo antifertility activity. Plumbagin belongs to the (Plumbaginaceae) family and mostly obtained from plant Plumbago indica Linn. Insolubility, instability and poor bioavailability are the factors which constrained in designing formulation of plumbagin. In order to overcome these factors, nanoparticles loaded plumbagin were formulated, this modified delivery system not only enhances the solubility and stability of plumbagin by reducing the particle size from thousands to a few hundred nanometers; when the size decreases, the active ingredient’s bioavailability increases. However, it also aids in enhancing the antifertility activity’s impact. Optimized formula was selected on the basis of design expert software and characterized. As a result, the optimized formula showed Particle size was 397.4 nm, shape of the nanoparticle was spherical detected by Scanning Electron Microscopy, Entrapment efficiency was 67.49 ± 0.047% and Zeta Potential was 25.0 mV. The disruption of the estrous cycle is indicated by the drop in FSH levels found in the in-vivo investigation. An in-vivo study reveals that the reproductive rate of albino wistar rats is decreasing. It was also discernible on the histology slide of the uterus and ovaries of the female albino rat. Follicle counts can yield valuable insights into the ovary’s functioning, particularly on the interplay between the mechanisms that control and facilitate folliculogenesis. At all test levels, no adverse symptoms were seen in any of the experimental groups after treatment. Due to high entrapment efficiency, stability, kinetics of release under simulated physiological conditions, and increased antifertility activity indicated that eudragit based nanoparticle formulation provide appropriate delivery system for Plumbagin.

Abstract 7173: Animal pharmacokinetics of an anti-Her2+ immunoliposome of docetaxel

Abstract Despite the success of docetaxel in combination with trastuzumab in HER2+ breast cancer, docetaxel still has serious limitations, including poor water solubility and the canonical systemic toxicity of taxanes. These side effects of taxanes need to be overcome to improve patient management. In this context, we have developed a nanoparticle drug delivery system. We have developed an immunoliposome loaded with docetaxel and grafted with trastuzumab using a microfluidic method by mixing an aqueous phase (KH2PO4 buffer) and an organic phase composed of phosphatidylcholine, cholesterol and PEGmal in a molar ratio of 50:31:1, to which docetaxel is added at a rate of 1.8% of the total lipid. We perform a thiolation reaction to graft the trastuzumab onto the polyethylene glycol chain. Resulting immunoliposomes were characterized by a mean diameter of 140 nm, a docetaxel encapsulation rate of 73% and a trastuzumab uptake rate of 400 units of trastuzumab by nanoparticle. C57BL/6 mice were administered with docetaxel 1.9 mg/kg and trastuzumab 160 ng/kg or a mixture of free drugs or as liposomes at the same dose by intraperitoneal injection. Blood was collected 1h, 2h, 3h, 6h, 8h and 24h after injection and plasma was analyzed by HPLC-UV with Paclitaxel as internal standard. For each treatment group, pharmacokinetic parameters and exposure metrics were calculated using PKanalix®: half-life T1/2, elimination rate constant Kel and area under the curve AUC at the end points (AUCtlast) and infinity (AUCinfinity). Statistical tests were performed with Sigmastats®. The results showed a marked change in pharmacokinetics with increased plasma exposure with liposomal docetaxel. Preliminary results show a longer half-life for liposomal docetaxel (40.76 h VS. 4.33 h, i.e., a 9.4-fold increase). The concentration of docetaxel appeared to decrease more rapidly between T1h and T6h with free docetaxel (Kel 0.16h-1) than with liposomal docetaxel (Kel 0.017h-1). The concentration of docetaxel reached a plateau over time, up to 24 hours (52.72± 9.45 ng/ml) in mice treated with immunoliposomes whereas Docetaxel was undetectable at T24h when treated with free drugs. There was a statistical difference in PK at T6h between liposomal docetaxel and free docetaxel, 69.86 ± 15.25 ng/ml and 53.67 ± 4.92 ng/ml, respectively (p < 0.001, non-paired t-test). Liposomal docetaxel showed higher AUC0-t (x3.75) and AUC0-∞ values (x5.9) compared to non-liposomal docetaxel. In conclusion, these preliminary results suggest that we have developed a promising immunoliposome for the systemic delivery of docetaxel in HER2+ breast cancer with sustained exposure. Citation Format: Mathilde Dacos, Erwan Diroff, Sarah Giacometti, Joseph Ciccolini, Raphaelle Fanciullino. Animal pharmacokinetics of an anti-Her2+ immunoliposome of docetaxel [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7173.

The Chemical Modification to Improve Solubility of Chitosan and Its Derivatives Application, Preparation Method, Toxicity as a Nanoparticles.

Chitosan is a functional polymer in the pharmaceutical field, including for nanoparticle drug delivery systems. Chitosan-based nanoparticles are a promising carrier for a wide range of therapeutic agents and can be administered in various routes. Solubility is the main problem for its production and utilization in large-scale industries. Chitosan modifications have been employed to enhance its solubility, including chemical modification. Many reviews have reported the chemical modification but have not focused on the specific characteristics obtained. This review focused on the modification to improve chitosan solubility. Additionally, this review also focused on the application of chitosan derivatives in nanoparticle drug delivery systems since very few similar reviews have been reported. The specific method for chitosan derivative-based nanoparticles was also reported and the latest report of chitosan, chitosan derivative, and chitosan toxicity were also described.

Revolutionizing Antiviral Therapeutics: Unveiling Innovative Approaches for Enhanced Drug Efficacy.

Since the beginning of the coronavirus pandemic in late 2019, viral infections have become one of the top three causes of mortality worldwide. Immunization and the use of immunomodulatory drugs are effective ways to prevent and treat viral infections. However, the primary therapy for managing viral infections remains antiviral and antiretroviral medication. Unfortunately, these drugs are often limited by physicochemical constraints such as low target selectivity and poor aqueous solubility. Although several modifications have been made to enhance the physicochemical characteristics and efficacy of these drugs, there are few published studies that summarize and compare these modifications. Our review systematically synthesized and discussed antiviral drug modification reports from publications indexed in Scopus, PubMed, and Google Scholar databases. We examined various approaches that were investigated to address physicochemical issues and increase activity, including liposomes, cocrystals, solid dispersions, salt modifications, and nanoparticle drug delivery systems. We were impressed by how well each strategy addressed physicochemical issues and improved antiviral activity. In conclusion, these modifications represent a promising way to improve the physicochemical characteristics, functionality, and effectiveness of antivirals in clinical therapy.

Research hotspots and trends of nanomaterials in stomatology: A bibliometric analysis from 2000 to 2023

BackgroundNanomaterials (NMs) have emerged as highly promising candidates for stomatology due to their excellent quality and remarkable progress in recent years. However, with the rapid expansion of the research scale, challenges arise in the technological decision-making and research management processes, and therefore difficulty for researchers to understand the knowledge structure and research hotspots has increased significantly. This study aims to make a comprehensive summary of authors, institutions, journals, research topics, development trends, and research hotspots of NMs in stomatology through bibliometric analysis for the sake of providing references for scientific decision-making, research management, and academic exploration in this filed. MethodsStudies on research and application of NMs in stomatology were retrieved from the Web of Science Core Collection (WoSCC) from January 1, 2000 to April 27, 2023. Bibliometric analysis and visualization were conducted using CiteSpace and VOSviewer. ResultsA total of 620 articles were included in this study, showing a gradual increase in the number of publications focusing on NMs in stomatology. Globally, China ranked first with 130 publications, and the United States (US) enjoyed the highest citation count (n = 5218) and average citation per paper (ACP) (n = 52.18). The top three institutions with the highest publication output were the University of Sao Paulo (n = 22), the Chinese Academy of Sciences (n = 20), and Shanghai Jiaotong University (n = 13). The journals MATERIALS and NANOMATERIALS emerged as the most popular in this field (n = 20), and BIOMATERIALS had the highest co-citations (n = 1597). The most prolific author was Dos Reis and Andrea Candido (n = 7), while Thomas J. Webster enjoyed the highest co-citations (n = 94). Burstness analysis of the references revealed a prominent research focus on nanoparticle drug delivery systems (specifically lipid nanoparticles). Keyword burstness analysis identified "oxide nanoparticle" as the primary frontier keyword in this field. ConclusionThis is the first study of using bibliometric analysis to summarize the research trends and frontiers of NMs in stomatology. With progressive advancements in the research and application of NMs in oral healthcare, their academic impact is steadily increasing. China and the US maintain a leading position in this field. Future directions could primarily focus on the development and application of nanoparticle drug delivery systems (especially lipid nanoparticles) and metal oxide nanoparticles (especially in antibacterial aspects). We hope that this bibliometric analysis could provide researchers with a panoramic view and useful references for future research, thus promoting the development of NMs in stomatology.

Alopecia areata: review of epidemiology, pathophysiology, current treatments and nanoparticulate delivery system.

Alopecia areata (AA) is a kind of alopecia that affects hair folliclesand nails. It typically comes with round patches and is a type of nonscarring hair loss. Various therapies are accessible for the management and treatment of AA, including topical, systemic and injectable modalities. It is a very complex type of autoimmune disease and is identified as round patches of hair loss and may occur at any age. This review paper highlights the epidemiology, clinical features, pathogenesis and new treatment options for AA, with a specific emphasis on nanoparticulate drug-delivery systems. By exploring these innovative treatment approaches, researchers aim to enhance the effectiveness and targeted delivery of therapeutic agents, ultimately improving outcomes for individuals living with AA.

Nanoparticle drug delivery systems responsive to tumor microenvironment: Promising alternatives in the treatment of triple-negative breast cancer.

The conventional therapeutic treatment of triple-negative breast cancer (TNBC) is negatively influenced by the development of tumor cell drug resistant, and systemic toxicity of therapeutic agents due to off-target activity. In accordance with research findings, nanoparticles (NPs) responsive to the tumor microenvironment (TME) have been discovered for providing opportunities to selectively target tumor cells via active targeting or Enhanced Permeability and Retention (EPR) effect. The combination of the TME control and therapeutic NPs offers promising solutions for improving the prognosis of the TNBC because the TME actively participates in tumor growth, metastasis, and drug resistance. The NP-based systems leverage stimulus-responsive mechanisms, such as low pH value, hypoxic, excessive secretion enzyme, concentration of glutathione (GSH)/reactive oxygen species (ROS), and high concentration of Adenosine triphosphate (ATP) to combat TNBC progression. Concurrently, NP-based stimulus-responsive introduces a novel approach for drug dosage design, administration, and modification of the pharmacokinetics of conventional chemotherapy and immunotherapy drugs. This review provides a comprehensive examination of the strengths, limitations, applications, perspectives, and future expectations of both novel and traditional stimulus-responsive NP-based drug delivery systems for improving outcomes in the medical practice of TNBC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Current approaches in tissue engineering-based nanotherapeutics for osteosarcoma treatment.

Osteosarcoma (OS) is a malignant bone neoplasm plagued by poor prognosis. Major treatment strategies include chemotherapy, radiotherapy, and surgery. Chemotherapy to treat OS has severe adverse effects due to systemic toxicity to healthy cells. A possible way to overcome the limitation is to utilize nanotechnology. Nanotherapeutics is an emerging approach in treating OS using nanoparticulate drug delivery systems. Surgical resection of OS leaves a critical bone defect requiring medical intervention. Recently, tissue engineered scaffolds have been reported to provide physical support to bone defects and aid multimodal treatment of OS. These scaffolds loaded with nanoparticulate delivery systems could also actively repress tumor growth and aid new bone formation. The rapid developments in nanotherapeutics and bone tissue engineering have paved the way for improved treatment efficacy for OS-related bone defects. This review focuses on current bifunctional nanomaterials-based tissue engineered (NTE) scaffolds that use novel approaches such as magnetic hyperthermia, photodynamic therapy, photothermal therapy, bioceramic and polymeric nanotherapeutics against OS. With further optimization and screening, NTE scaffolds could meet clinical applications for treating OS patients.

A comprehensive review on alpha-lipoic acid delivery by nanoparticles.

Alpha-lipoic acid (ALA) has garnered significant attention for its potential therapeutic benefits across a wide spectrum of health conditions. Despite its remarkable antioxidant properties, ALA is hindered by challenges such as low bioavailability, short half-life, and unpleasant odor. To overcome these limitations and enhance ALA's therapeutic efficacy, various nanoparticulate drug delivery systems have been explored. This comprehensive review evaluates the application of different nanoparticulate carriers, including lipid-based nanoparticles (solid lipid nanoparticles, niosomes, liposomes, nanostructured lipid carriers (NLCs), and micelles), nanoemulsions, polymeric nanoparticles (nanocapsules, PEGylated nanoparticles, and polycaprolactone nanoparticles), films, nanofibers, and gold nanoparticles, for ALA delivery. Each nanoparticulate system offers unique advantages, such as improved stability, sustained release, enhanced bioavailability, and targeted delivery. For example, ALA-loaded SLNs demonstrated benefits for skin care products and skin rejuvenation. ALA encapsulated in niosomes showed potential for treating cerebral ischemia, a condition largely linked to stroke. ALA-loaded cationic nanoemulsions showed promise for ophthalmic applications, reducing vascular injuries, and corneal disorders. Coating liposomes with chitosan further enhanced stability and performance, promoting drug absorption through the skin. This review provides a comprehensive overview of the advancements in nanoparticulate delivery systems for ALA, highlighting their potential to overcome the limitations of ALA administration and significantly enhance its therapeutic effectiveness. These innovative approaches hold promise for the development of improved ALA-based treatments across a broad spectrum of health conditions.

Design, optimization, and characterization of covalent organic framework-based nanoparticle drug delivery systems

Drug delivery system has became a research hotspot due to its excellent targeting ability and drug-controlled releases. Herein, a hierarchically flower-like hollow COF (HFH-COF) is synthesized via a simple one-step reaction method at room temperature. The as-prepared HFH-COF has high specific surface area, uniform pore size and pH sensitivity. Based on drug loading experiments using Adriamycin (DOX) as a model molecule, HFH-COF exhibits high drug loading capabilities. The drug release curves under different pH conditions show that HFH-COF is pH sensitive. In vitro cell experiments further confirmed that HFH-COF has good biocompatibility. DOX can be effectively released from HFH-COF to kill tumor cells. The as-prepared HFH-COF drug-loading system has exceptional drug loading ability, excellent biocompatibility, pH sensitivity of the tumor microenvironment, as well as good the potential application prospects in tumor treatment. Overall, a new COF-based drug delivery systems have been developed, and COFs are expanding the field of drug carriers as well.

Versatile Nanoparticulate Systems as a Prosperous Platform for Targeted Nose-Brain Drug Delivery.

The intranasal route has proven to be a reliable and promising route for delivering therapeutics to the central nervous system (CNS), averting the blood-brain barrier (BBB) and avoiding extensive first-pass metabolism of some drugs, with minimal systemic exposure. This is considered to be the main problem associated with other routes of drug delivery such as oral, parenteral, and transdermal, among other administration methods. The intranasal route maximizes drug bioavailability, particularly those susceptible to enzymatic degradation such as peptides and proteins. This review will stipulate an overview of the intranasal route as a channel for drug delivery, including its benefits and drawbacks, as well as different mechanisms of CNS drug targeting using nanoparticulate drug delivery systems devices; it also focuses on pharmaceutical dosage forms such as drops, sprays, or gels via the nasal route comprising different polymers, absorption promoters, CNS ligands, and permeation enhancers.