Nanoparticulate Drug Delivery Systems Research Articles

The Other Side of Plastics: Bioplastic-Based Nanoparticles for Drug Delivery Systems in the Brain.

Plastics have changed human lives, finding a broad range of applications from packaging to medical devices. However, plastics can degrade into microscopic forms known as micro- and nanoplastics, which have raised concerns about their accumulation in the environment but mainly about the potential risk to human health. Recently, biodegradable plastic materials have been introduced on the market. These polymers are biodegradable but also bioresorbable and, indeed, are fundamental tools for drug formulations, thanks to their transient ability to pass through biological barriers and concentrate in specific tissues. However, this "other side" of bioplastics raises concerns about their toxic potential, in the form of micro- and nanoparticles, due to easier and faster tissue accumulation, with unknown long-term biological effects. This review aims to provide an update on bioplastic-based particles by analyzing the advantages and drawbacks of their potential use as components of innovative formulations for brain diseases. However, a critical analysis of the literature indicates the need for further studies to assess the safety of bioplastic micro- and nanoparticles despite they appear as promising tools for several nanomedicine applications.

A pH‐responsive nanoparticle delivery system containing dihydralazine and doxorubicin‐based prodrug for enhancing antitumor efficacy

AbstractThe efficacy of nanoparticle (NP)‐based drug delivery technology is hampered by aberrant tumor stromal microenvironments (TSMs) that hinder NP transportation. Therefore, the promotion of NP permeation into deep tumor sites via the regulation of tumor microenvironments is of critical importance. Herein, we propose a potential solution using a dihydralazine (HDZ)‐loaded nanoparticle drug delivery system containing a pH‐responsive, cyclic RGD peptide‐modified prodrug based on doxorubicin (cRGD‐Dex‐DOX). With a combined experimental and theoretical approach, we find that the designed NP system can recognize the acid tumor environments and precisely release the encapsulated HDZ into tumor tissues. HDZ can notably downregulate the expression levels of hypoxia‐inducible factor 1α (HIF1α), α‐smooth muscle actin, and fibronectin through the dilation of tumor blood vessels. These changes in the TSMs enhance the enrichment and penetration of NPs and also unexpectedly promote the infiltration of activated T cells into tumors, suggesting that such a system may offer an effective “multifunctional therapy” through both improving the chemotherapeutic effect and enhancing the immune response to tumors. In vivo experiments on 4T1 breast cancer bearing mice indeed validate that this therapy has the most outstanding antitumor effects over all the other tested control regimens, with the lowest side effects as well.

Advances in the use of cell-membrane encapsulated nanoparticles to target tumor drugs

<p style="text-align: justify;">Cancer treatment faces multiple challenges, including tumor heterogeneity, drug resistance, microenvironment influence, treatment side effects, and treatment cost. The heterogeneity of the tumor makes the effect of the same treatment vary in different patients, so the development of personalized treatment strategies is crucial. In addition, resistance of tumor cells to therapeutic drugs is a major challenge, and new strategies to overcome resistance are needed. As a cutting-edge field of science and technology, nanotechnology has brought great potential and opportunities for tumor treatment. Nanoparticle drug delivery systems improve drug efficacy and reduce side effects through precise targeted delivery and controlled release. Cell-membrane coated nanoparticles show great promise in tumor therapy. Nanoparticles coated with cell membranes have good biocompatibility, can reduce the obstacles of immune rejection and cell uptake, improve the accumulation and retention of drugs in tumor tissues, and have good drug delivery ability, drug stability and control release ability. This review discusses advances in the use of cell-membrane coated nanoparticles to target tumor drugs.</p>

Bone-Targeted Nanoparticle Drug Delivery System-Mediated Macrophage Modulation for Enhanced Fracture Healing.

Despite decades of progress, developing minimally invasive bone-specific drug delivery systems (DDS) to improve fracture healing remains a significant clinical challenge. To address this critical therapeutic need, nanoparticle (NP) DDS comprised of poly(styrene-alt-maleic anhydride)-b-poly(styrene) (PSMA-b-PS) functionalized with a peptide that targets tartrate-resistant acid phosphatase (TRAP) and achieves preferential fracture accumulation has been developed. The delivery of AR28, a glycogen synthase kinase-3 beta (GSK3β) inhibitor, via the TRAP binding peptide-NP (TBP-NP) expedites fracture healing. Interestingly, however, NPs are predominantly taken up by fracture-associated macrophages rather than cells typically associated with fracture healing. Therefore, the underlying mechanism of healing via TBP-NP is comprehensively investigated herein. TBP-NPAR28 promotes M2 macrophage polarization and enhances osteogenesis in preosteoblast-macrophage co-cultures in vitro. Longitudinal analysis of TBP-NPAR28 -mediated fracture healing reveals distinct spatial distributions of M2 macrophages, an increased M2/M1 ratio, and upregulation of anti-inflammatory and downregulated pro-inflammatory genes compared to controls. This work demonstrates the underlying therapeutic mechanism of bone-targeted NP DDS, which leverages macrophages as druggable targets and modulates M2 macrophage polarization to enhance fracture healing, highlighting the therapeutic benefit of this approach for fractures and bone-associated diseases.

The Effect of Beta-lactoglobulin Nanocapsules Containing Astaxanthin and 5-fluorouracil on the Antioxidant Enzymes Activity of Superoxide Dismutase, Catalase and Glutathione Peroxidase in HCT116 Colorectal Cancer Cell Line

Background: The use of nanoparticle drug delivery systems to enhance the therapeutic efficacy and reduce the side effects of anticancer drugs is taken into consideration. Astaxanthin (ATX) is a natural xanthophyll carotenoid with antioxidant, anti-inflammatory, and antiapoptotic properties used to prevent and treat some cancers. Objectives: In the present study, the antioxidant effect of beta-lactoglobulin (β-LG) nanocapsules containing ATX and 5-fluorouracil (5-FU; the first-line therapy for colorectal cancer) on the antioxidant enzymes activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) in HCT116 colorectal cancer cell line was examined. Methods: In this experimental study, HCT116 cells were treated with different treatments of encapsulation of ATX in β-LG, encapsulation 5-FU in β-LG, co-encapsulation of ATX and 5-FU in β-LG, free ATX, free 5-FU, free ATX and free 5-FU, or β-LG nanocapsules without drugs for 24, 48 and 72 hours. There is a control group in which HCT116 cells were not treated with any drug. Then, 50% inhibitory concentration (IC50) and cell viability were determined using an MTT assay. The antioxidant enzyme activity of SOD, CAT, and GPX was measured by a colorimetric method in HCT116 cells. Results: Different treatments reduced the cell viability and increased apoptotic cells in a timedependent manner, which was significant for beta-lactoglobulin nanocapsules treatment (P<0.05). It means receiving more 5-FU or ATX in the encapsulated form by HCT116 cells. The antioxidant enzyme activity of SOD, CAT, and GPX in HCT116 cells treated with beta-lactoglobulin nanocapsule treatment significantly increased compared to the control group (P<0.001). Moreover, the antioxidant activity of these enzymes in different treatments containing ATX (free or encapsulation) was significantly higher than in other treatments (P<0.05). The most increase in the activity of antioxidant enzymes is recorded in the treatment of nanocapsules containing ATX and 5-FU simultaneously. Conclusion: Increased activity of antioxidant enzymes in addition to the induction of apoptosis in colorectal cancer cells by various treatments of beta-lactoglobulin nanocapsules indicates more effective drug administration in encapsulated form as well as synergistic thera[peutic effects of ATX and 5-FU. Moreover, the main increase in antioxidant enzyme activity may be related to ATX.

Current Application of Nanoparticle Drug Delivery Systems to the Treatment of Anaplastic Thyroid Carcinomas.

Anaplastic thyroid carcinomas (ATCs) are a rare subtype of thyroid cancers with a low incidence but extremely high invasiveness and fatality. The treatment of ATCs is very challenging, and currently, a comprehensive individualized therapeutic strategy involving surgery, radiotherapy (RT), chemotherapy, BRAF/MEK inhibitors (BRAFi/MEKi) and immunotherapy is preferred. For ATC patients in stage IVA/IVB, a surgery-based comprehensive strategy may provide survival benefits. Unfortunately, ATC patients in IVC stage barely get benefits from the current treatment. Recently, nanoparticle delivery of siRNAs, targeted drugs, cytotoxic drugs, photosensitizers and other agents is considered as a promising anti-cancer treatment. Nanoparticle drug delivery systems have been mainly explored in the treatment of differentiated thyroid cancer (DTC). With the rapid development of drug delivery techniques and nanomaterials, using hybrid nanoparticles as the drug carrier to deliver siRNAs, targeted drugs, immune drugs, chemotherapy drugs and phototherapy drugs to ATC patients have become a hot research field. This review aims to describe latest findings of nanoparticle drug delivery systems in the treatment of ATCs, thus providing references for the further analyses.

Potential targets and applications of nanodrug targeting myeloid cells in osteosarcoma for the enhancement of immunotherapy.

Targeted immunotherapies have emerged as a transformative approach in cancer treatment, offering enhanced specificity to tumor cells, and minimizing damage to healthy tissues. The targeted treatment of the tumor immune system has become clinically applicable, demonstrating significant anti-tumor activity in both early and late-stage malignancies, subsequently enhancing long-term survival rates. The most frequent and significant targeted therapies for the tumor immune system are executed through the utilization of checkpoint inhibitor antibodies and chimeric antigen receptor T cell treatment. However, when using immunotherapeutic drugs or combined treatments for solid tumors like osteosarcoma, challenges arise due to limited efficacy or the induction of severe cytotoxicity. Utilizing nanoparticle drug delivery systems to target tumor-associated macrophages and bone marrow-derived suppressor cells is a promising and attractive immunotherapeutic approach. This is because these bone marrow cells often exert immunosuppressive effects in the tumor microenvironment, promoting tumor progression, metastasis, and the development of drug resistance. Moreover, given the propensity of myeloid cells to engulf nanoparticles and microparticles, they are logical therapeutic targets. Therefore, we have discussed the mechanisms of nanomedicine-based enhancement of immune therapy through targeting myeloid cells in osteosarcoma, and how the related therapeutic strategies well adapt to immunotherapy from perspectives such as promoting immunogenic cell death with nanoparticles, regulating the proportion of various cellular subgroups in tumor-associated macrophages, interaction with myeloid cell receptor ligands, activating immunostimulatory signaling pathways, altering myeloid cell epigenetics, and modulating the intensity of immunostimulation. We also explored the clinical implementations of immunotherapy grounded on nanomedicine.

P10.22.B COMBINATION OF ARTS MIMETICS WITH AUTOPHAGY INHIBITORS AS A NOVEL THERAPEUTIC STRATEGY TO OVERCOME APOPTOSIS RESISTANCE IN GLIOBLASTOMA

Abstract BACKGROUND Glioblastoma (GBM) is the most common malignant brain tumour in adults. The current standard of care for GBM patients consists of maximal surgical resection followed by chemotherapy and radiation. Despite such an aggressive treatment approach, the average 5-year survival rate for GBM patients is approximately 5%. One of the main reasons for poor therapy response in the GBM is resistance to programmed cell death, otherwise known as apoptosis. One of the mechanisms behind apoptosis resistance relies on the upregulation of inhibitor of apoptosis proteins (IAPs) which are known to hinder pro-apoptotic proteins and allow cell survival under abnormal conditions such as severe DNA damage. However, there are natural IAP antagonists such as ARTS which are capable of stimulating cell death by promoting the degradation of IAPs. To harness the pro-apoptotic function of IAP antagonists, small peptide mimetics of ARTS have been developed. This project investigates the efficacy of utilizing ARTS mimetics as a novel strategy to overcome apoptosis resistance in the GBM treatment. MATERIAL AND METHODS This study utilizes patient-derived cells with exogenous gain-of-function (GOF) overexpression to introduce full-length ARTS protein as well as pharmacological small peptide mimetics of ARTS to evaluate the response of GBM cells following the promotion of ARTS activity. We also employ a patient-derived orthotopic xenograft mouse model to test novel combinatorial strategies in vivo, where we used a nanoparticle drug delivery system to ensure treatment delivery across the blood-brain barrier (BBB). RESULTS We found that patient-derived GBM cells were highly resistant to ARTS-induced apoptosis. Further molecular investigation unveiled a novel role of ARTS in the upregulation of autophagy as a resistance mechanism. A combination of ARTS GOF or mimetic peptides with autophagy inhibitors mitigated resistance to ARTS-mediated apoptosis and drastically decreased GBM cell proliferation. This combination was further tested in the patient-derived xenograft mouse model, which demonstrated the successful delivery of ARTS mimetic peptides and autophagy inhibitors through the BBB via nanoparticle lipid carriers. Animals treated with a combination of the autophagy inhibitor Spautin-1 and ARTS mimetic peptides demonstrated significantly prolonged survival, confirming the therapeutic potential of such combinatorial approach for GBM treatment. CONCLUSION Altogether, these findings uncover a previously unknown role of ARTS in autophagy regulation and provide evidence that the combination of IAP-antagonist mimetics with autophagy inhibitors can be an effective strategy against highly aggressive GBM brain tumours. This work was supported by the Health Sciences Centre Foundation (HSCF).

Application of Nanoparticle Drug Delivery Systems in the Medical Field: Focusing on Functionalized Gold Nanomaterials

Nanoparticle drug delivery systems are currently one of the hottest topics in the field of medicine. They can precisely deliver drugs to the parts of the patient that need treatment, with the goal of improving patient effectiveness and reducing drug toxicity. Gold nanoparticles (AuNPs) are considered one of the most promising nanomaterials due to their unique optical, electronic, sensing, and biochemical properties. By combining AuNPs with different ligands, functionalized gold nanoparticle (F-AuNPs) drug delivery systems can be obtained, which have broad application prospects in the field of medicine. This article focuses on the different ligand connection types of F-AuNPs and reviews the research progress of F-AuNPs drug delivery systems in the field of medicine in recent years.

Nanoparticle: A unique strategy for Antifungal agents.

Nanomaterials are emerging as an innovative and efficient instrument for the transport and cellular translocation of therapeutic compounds, namely, biopharmaceuticals. The use of nanoparticles as drug carriers in the healthcare industry, for instance, in several applications, with drug delivery being among the most significant. These nanomaterials are adaptable and have qualities that are good for delivering compounds that are biologically active. The creation of different nanoparticles as a drug delivery system has led to the development of a variety of nanoparticulate drug delivery systems to reduce toxicity, reduce the dosing system, and increase the viability of the drug. The objectives of this review are to provide an overview of the recent advances in nanotechnology in Antifungal treatment and to overcome the problems associated with antifungal agents.

Evaluation of Folate-Functionalized Nanoparticle Drug Delivery Systems-Effectiveness and Concerns.

Targeting folate receptors is a potential solution to low tumor selectivity concerning conventional chemotherapeutics. Apart from antibody-drug conjugates, folate-functionalized nanoparticle drug delivery systems are interesting to be explored due to many advantages, yet currently, none seems to enter the clinical trials. Multiple in vitro evidence is available to support its efficacy compared to the non-targeting carrier and free drug formulation. Additionally, several studies pointed out factors affecting its effectiveness, including surface properties and endosomal trapping. However, in vivo biodistribution studies revealed issues that may arise from folate receptor targeting, including rapid liver uptake, subsequently reducing the nanoparticles' tumor uptake. This issue may be due to the folate receptor β expressed by the activated macrophages in the liver; route of administration and tumor location might also influence the targeting effectiveness. Moreover, it is perplexing to generalize nanoparticles reported from various publications, primarily due to the different formulations, lack of characterization, and experimental settings, making it harder to determine the accurate factor influencing targeting effectiveness.

Metal Nanoparticles as Novel Drug Delivery Systems: A Review of Current Challenges and Opportunities

Nanotechnology's intriguing characteristics have attracted a lot of study in recent years. Nanomaterials, nanoelectronics, and nanobiotechnology are all subfields of nanotechnology that share a great deal of common ground. The possibility for metal nanoparticles (MNPs) to completely transform treatment is what has made them so remarkable. In addition to avoid antibiotic resistance and improving medication delivery, MNPs have been shown to raise the efficacy index of medicines. Additionally, MNPs have applications in in vitro and in vivo tests, improved biodegradable substance production, and nutraceuticals. Improved targeting at the necessary target location is one major benefit of using metallic nanoparticles for drug delivery systems due to their improved durability and half-life in circulation. Bio-nanotechnology is expanding into the new field of green synthesis of MNPs, which is more environmentally friendly than traditional chemical and physical synthesis techniques. Focusing on environmentally friendly approaches to the preparation, surface modification, and applications of various MNPs like silver, gold, platinum, palladium, copper, zinc oxide, metal sulfide, and nanometal organic frameworks, this review seeks to present current insights into the challenges and perspectives of MNPs in drug delivery systems.

Effect of Nanoparticle Weight on the Cellular Uptake and Drug Delivery Potential of PLGA Nanoparticles.

Biodegradable and biocompatible polymeric nanoparticles (NPs) stand out as a key tool for improving drug bioavailability, reducing the inherent toxicity, and targeting the intended site. Most importantly, the ease of polymer synthesis and its derivatization to add functional properties makes them potentially ideal to fulfill the requirements for intended therapeutic applications. Among many polymers, US FDA-approved poly(l-lactic-co-glycolic) acid (PLGA) is a widely used biocompatible and biodegradable co-polymer in drug delivery and in implantable biomaterials. While many studies have been conducted using PLGA NPs as a drug delivery system, less attention has been given to understanding the effect of NP weight on cellular behaviors such as uptake. Here we discuss the synthesis of PLGA NPs with varying NP weights and their colloidal and biological properties. Following nanoprecipitation, we have synthesized PLGA NP sizes ranging from 60 to 100 nm by varying the initial PLGA feed in the system. These NPs were found to be stable for a prolonged period in colloidal conditions. We further studied cellular uptake and found that these NPs are cytocompatible; however, they are differentially uptaken by cancer and immune cells, which are greatly influenced by NPs' weight. The drug delivery potential of these nanoparticles (NPs) was assessed using doxorubicin (DOX) as a model drug, loaded into the NP core at a concentration of 7.0 ± 0.5 wt % to study its therapeutic effects. The results showed that both concentration and treatment time are crucial factors for exhibiting therapeutic effects, as observed with DOX-NPs exhibiting a higher potency at lower concentrations. The observations revealed that DOX-NPs exhibited a higher cellular uptake of DOX compared to the free-DOX treatment group. This will allow us to reduce the recommended dose to achieve the desired effect, which otherwise required a large dose when treated with free DOX. Considering the significance of PLGA-based nanoparticle drug delivery systems, we anticipate that this study will contribute to the establishment of design considerations and guidelines for the therapeutic applications of nanoparticles.

Dissecting the Role of SMYD2 and Its Inhibitor (LLY-507) in the Treatment of Chemically Induced Non-Small Cell Lung Cancer (NSCLC) by Using Fe3O4 Nanoparticles Drug Delivery System.

Cancer therapies based on nanoparticles with a loaded drug can overcome the problem of the drug's toxic effects in the traditional chemotherapeutic approach. In this study, we loaded LLY-507, a potent inhibitor of SMYD2, a methyltransferase enzyme, on iron oxide nanoparticles (IONPs). The prepared nanoparticles were characterized by microscopic analysis, loading efficiency, and drug release studies. Microscopic examination revealed an average grain size of 44 nm. The in vitro effect of LLY-507-IONPs, LLY-507, and IONPs was determined by MTT analysis (A549 cells) and hemolysis studies. IONPs have almost negative hemolytic activity in blood. The cell viability assay revealed IC50 values of both LLY-507 alone and LLY-507-loaded IONPs against A549; the lower value of the drug loaded on NPs (0.71 µg/mL alone and 0.53 µg/mL loaded on NPs) shows strong synergistic anticancer potential. We further tested the role of loaded NPs in a urethane-induced lung cancer mouse model (n = 40 mice in three independent trials, 20 mice in control group) to check the role of SMYD2 at various time points of lung cancer development. The loss of SMYD2 due to LLY-507 suppressed tumor growth, emphysema, hemorrhage, and congestion considerably. Hence, it can be concluded that the SMYD2 inhibitor has an anti-inflammatory effect on the mouse lung and suppresses tumor growth by inhibiting the SMYD2 protein.

Oral Nano-Delivery Systems for Colon-Targeted Drug Delivery of Traditional Chinese Medicine in Ulcerative Colitis

Ulcerative colitis (UC) is a type of inflammatory bowel disease with a high recurrence rate. In this regard, sulfasalazine and immunosuppressive medications are often used for an extended period in clinical practice, but their effectiveness is limited, and they are prone to side effects. Modern research has shown that herbal active ingredients of Traditional Chinese Medicine (TCM), such as polyphenols, alkaloids, quinones, and terpenes, have a promising impact on treating UC via a multi-target mechanism and with low side effects. Poor water solubility and low bioavailability of these agents in the gastrointestinal tract are the most challenging issues in delivering these agents to the target tissues. Researchers have created a variety of oral colon-targeted nano-systems of TCM active ingredients in response to the above formulation issues, which significantly improve the treatment of UC by avoiding gastrointestinal damage, prolonging intestinal retention, and achieving controlled drug release at the lesion site. In order to provide ideas for the oral-targeted treatment of UC with active ingredients from TCM, the research progress of an oral colon-targeted nano-system for the treatment of UC is reviewed in the current study, as well as the research progress of an oral colon-targeted nano-system for the treatment of UC. Keywords: Medicine, Chinese Traditional, Colitis, Ulcerative, Nanoparticle Drug Delivery System.

Doxorubicin-loaded mPEG-pPAd-mPEG triblock polymeric nanoparticles for drug delivery systems: Preparation and in vitro evaluation

Conventional methods in chemotherapy and radiotherapy do not target tumor sites treating breast cancer. Therefore, they cause some extra adverse effects on healthy tissues and cells, which bring fatal results. In recent applications, drug delivery systems have been used to target tumors directly or their environment indirectly. The new approach has attracted considerable interest due to its promise to overcome breast cancer with little adverse effect. Synthetic or natural polymer shell capsules are generally used to deliver therapeutic agents due to their biocompatibility and biodegradability. Doxorubicin (DOX), a convenient chemotherapeutic agent, was encapsulated using produced monomethyl ether ended poly(ethylene glycol)-poly(propylene adipate)- monomethyl ether ended poly(ethylene glycol) (mPEG-pPAd-mPEG) triblock copolymers in this study. The nanoparticle form of the prepared mPEG-pPAd-mPEG tri-block copolymer system was produced by a double emulsion-solvent evaporation method. To prepare triblock copolymer, firstly, poly (propylene adipate) (pPAd) was synthesized and characterized by using Fourier Transform Infrared (FT-IR) spectroscopy structurally and end-group analysis method to determine the number average molecular weight. The nanoparticle's size characteristics were measured by the Dynamic Light Scattering (DLS) method, while encapsulation efficacy and DOX-release profile were determined by spectrofluorometer instrument. Following the production of the nanoparticles, the antiproliferative effect and cellular uptake efficiency of the mPEG-pPAd-mPEG nanoparticles (PANPs), the doxorubicin-loaded mPEG-pPAd-mPEG nanoparticles (DPANPs), ICG-loaded mPEG-pPAd-mPEG nanoparticles (IPANPs), free-DOX, and free-ICG were tested on MCF-7 and MDA-MB-231 breast cancer cell line. The cytotoxicity analysis revealed that the DPANPs exhibited low toxicity compared to free-DOX. The physical and chemical analysis showed that the nanoparticles produced within this study's scope could be used as new drug delivery systems for breast cancer treatment.

Onto the differences in formulating micro-/nanoparticulate drug delivery system from Thai silk and Vietnamese silk: A critical comparison

Silk fibroin is a natural polymer with physicochemical properties heavily dependent on its silkworm sources and cultivation conditions. Hence, this study critically compared the characteristics and capacity to generate micro-/nanoparticles of fibroin extracted from the Thai silk and Vietnamese silk. Both Thai fibroin (SFT) and Vietnamese fibroin (SFV) were extracted and fabricated into micro-/nanoparticles using the same methods of desalination and condensation, respectively. Firstly, the amino acid compositions of SFT and SFV were determined and found to be similar, suggesting that the different cultivation conditions did not alter the fibroin chemical contents. Secondly, utilizing various analytical techniques, the SFT structure revealed less heavy chains, more light chains and P-25 glycoproteins, and lower crystallinity than those of SFV. Accordingly, compared to the particles formed by SFT, the SFV-based particles were significantly bigger (∼1700 nm vs. ∼150 nm), and possessed less drug (Amphotericin B) entrapment efficiency (64.3 ± 4.4% vs. 79.3 ± 5.1%), higher hemototoxicity, and less biostability in the blood. Conclusively, these differences add more insights for the appropriate applications of each fibroin kind to best promote its qualities and effectiveness.

Recent and advanced therapy for oral cancer.

Oral cancer is a common and deadly kind of tissue invasion, has a high death rate, and may induce metastasis that mostly affects adults over the age of 40. Most in vitro traditional methods for studying cancer have included the use of monolayer cell cultures and several animal models. There is a worldwide effort underway to reduce the excessive use of laboratory animals since, although being physiologically adequate, animal models rarely succeed in exactly mimicking human models. 3D culture models have gained great attention in the area of biomedicine because of their capacity to replicate parent tissue. There are many benefits to using a drug delivery approach based on nanoparticles in cancer treatment. Because of this, in vitro test methodologies are crucial for evaluating the efficacy of prospective novel nanoparticle drug delivery systems. This review discusses current advances in the utility of 3D cell culture models including multicellular spheroids, patient-derived explant cultures, organoids, xenografts, 3D bioprinting, and organoid-on-a-chip models. Aspects of nanoparticle-based drug discovery that have utilized 2D and 3D cultures for a better understanding of genes implicated in oral cancers are also included in this review.

Preparation and Characterization of 5‐Fluorouracil Loaded Cellulose and Exosome Nanocarriers: Sustained Release Behavior and Cytotoxicity Studies**

AbstractIn recent years, much effort has been devoted to designing nanoparticle drug delivery systems and improving the efficacy of anticancer drugs. This study focused on the preparation of a novel biocompatible nanocarrier based on bacterial cellulose (BC) in the presence of exosome (Exo) for the controlled release of 5‐fluorouracil (5‐FU), known as 5‐FU.Exo@BC. The physicochemical properties of 5‐FU.Exo@BC were thoroughly characterized using field emission scanning electron microscopy (FESEM), differential scanning calorimetry (DSC), Fourier‐transform infrared spectroscopy (FTIR), and X‐ray diffraction (XRD). These results confirmed the successful preparation of 5‐FU.Exo@BC. The release behavior of 5‐FU.Exo@BC compared with 5‐FU and 5‐FU@BC demonstrated a significant sustained release over 162 h. The release mechanism of the above three systems followed Korsmeyer‐Peppas with non‐Fickian diffusion for 5‐FU@BC and 5‐FU.Exo@BC. Furthermore, the viability of HT‐29 cells (human colon cancer cell lines) against BC, 5‐FU@BC and 5‐FU.Exo@BC indicated that 5‐FU has promising efficacy in 5‐FU.Exo@BC system. Subsequently, the prepared bio‐nanocomposite could be suggested as a potential drug delivery system with an effective controlled‐release function.

Nanoparticle drug delivery to target breast cancer brain metastasis: Current and future trends.

Breast cancer brain metastasis (BCBM) is rapidly becoming an impediment to continuing survival gains seen in breast cancer patients. Drug delivery across the blood-brain barrier is the main issue hindering systemic therapy against BCBM. This review details recent advances in nanoparticle (NP) drug delivery systems to target BCBM. Their primary benefits are: enhanced circulating and intra-BCBM drug biodistribution, BCBM targeting through NP functionalization, opportunities for gene manipulation and their theragnostic applications. Multiple NPs have been synthesized to deliver therapeutic HER2 blockade, which is particularly important given HER2-positive breast cancer's tendency to form BCBM. Finally, we review the clinical context in which NP-based therapeutics have been investigated in BCBM patients. While a breakthrough in improving patient outcomes remain awaited, these clinical trials represent positive steps in the changing attitude towards BCBM as a treatable illness. Although multiple challenges remain in the clinical translation of BCBM-directed NP therapies, ongoing research in the field offers promising avenues for novel targeting of this devastating disease.