Nanoparticles For Drug Delivery Research Articles

Role of Nano Particle Drug Delivery System in Antifungal Therapy

Effective illnesses are currently treated with oral and common effective strategies. Oral and effective courses encounter numerous challenges, including pharmaceutical drug interactions, higher metabolic rate, unfavorable retention, and toxicity. Controlled drug release has not been demonstrated using conventionally useful measuring forms such as gels, salves, and creams. According to written accounts, several lakhs of people are affected and over 1.5 lakh people are thought to have died as a result of infectious contaminations. The high prevalence of parasite infections, which has been disrupted by an expansion in inclination factors, has become a concerning general medical issue. It is essential to thoroughly investigate the relationships between the specifics, the organization method, pharmacological properties, pharmacokinetics, pharmacodynamics, strength, sufficiency, safety, and clinical signs in order to improve a successful novel antifungal medication delivery framework. This audit article looks at several types of nanoparticle processes that are used to deliver antifungal drugs, such as dendrimers, polymeric nanoparticles, inorganic nanoparticles, and nanoparticles based on phospholipids (nanovesicles).

Synthesis Characterization and Adsorption of doxorubicin hydrochloride on SiO2 nanoparticle for drug delivery

في هذه الدراسة، تم استخدام رباعي إيثيل أورثوسيليكات (TEOS) والبولي إيثيلين جلايكول 5٪ وحمض الهيدروكلوريك 0.001 نورمالي لإنشاء جسيمات السيليكا النانوية كيميائيا (SiO2 NPs). تم تصنيع جسيمات السيليكا النانوية المحملة بدوكسوروبيسين (DOX) (DOX / SiO2) ، والتي يتم تطبيقها بشكل شائع كجزء من أنظمة توصيل الأدوية في علاج السرطان ، باستخدام طريقة سول جل. تمت دراسة التشكل والمحتوى السطحي للجسيمات النانوية المحملة ب DOX / السيليكا المنتجة باستخدام تقنيات مختلفة بما في ذلك حيود الأشعة السينية (XRD) ، والمجهر الإلكتروني الماسح (SEM) ، وطيف التحليل الطيفي بالأشعة تحت الحمراء (FTIR). يبلغ قطر DOX / SiO2 المركب 38 نانومتر. يتبع الامتزاز متساوي الحرارة متساوي الحرارة Freundlich وحركية الامتزاز المناسبة للترتيب الثاني الزائف. كانت قيم R2 لنماذج Freundlich و Langmuir 0.9931 و 0.9731 ، على التوالي ، مما يدل على أن متساوي الحرارة Freundlich يميل إلى أن يكون أكثر ملاءمة مع البيانات التجريبية مقارنة بنموذج Langmuir. تهدف هذه الدراسة إلى استخدام تقنية النانو في توصيل الدواء، وبالتالي التغلب على عيوب DDS الشائعة.

Cubosomes and hexosomes stabilized by sorbitan monooleate as biocompatible nanoplatforms against skin metastatic human melanoma

Nanoparticles have become versatile assets in the medical field, providing notable benefits across diverse medical arenas including controlled drug delivery, imaging, and immunological assays. Among these, non-lamellar lipid nanoparticles, notably cubosomes and hexosomes, showcase remarkable biocompatibility and stability, rendering them as optimal choices for theranostic applications. Particularly, incorporating edge activators like sodium taurocholate enhances the potential of these nanoparticles for dermal and transdermal drug delivery, overcoming the stratum corneum, a first line of defense in our skin. This study reports on the formulation of monoolein-based cubosomes and hexosomes incorporating taurocholate and stabilized by Span 80 and co-encapsulating Chlorin e6 and coenzyme QH for photodynamic therapy in skin metastatic melanoma. The formulations were optimized using small-angle X-ray scattering, and cryo-transmission electron microscopy confirmed the presence of cubosomes or hexosomes, depending on the ratio between taurocholate and Span 80. Furthermore, the co-loaded nanoparticles exhibited high encapsulation efficiencies for both Ce6 and the coenzyme QH. In vitro studies on human melanoma cells (Me45) demonstrated the biocompatibility and photodynamic activity of the loaded formulations. These findings show the possibility of formulating more biocompatible cubosomes and hexosomes for photodynamic therapy in skin cancer treatment.

Application of PPAR Ligands and Nanoparticle Technology in Metabolic Steatohepatitis Treatment.

Metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH) is a major disease worldwide whose effective treatment is challenging. Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily and function as ligand-activated transcription factors. To date, three distinct subtypes of PPARs have been characterized: PPARα, PPARβ/δ, and PPARγ. PPARα and PPARγ are crucial regulators of lipid metabolism that modulate the transcription of genes involved in fatty acid (FA), bile acid, and cholesterol metabolism. Many PPAR agonists, including natural (FAs, eicosanoids, and phospholipids) and synthetic (fibrate, thiazolidinedione, glitazar, and elafibranor) agonists, have been developed. Furthermore, recent advancements in nanoparticles (NPs) have led to the development of new strategies for MASLD/MASH therapy. This review discusses the applications of specific cell-targeted NPs and highlights the potential of PPARα- and PPARγ-targeted NP drug delivery systems for MASLD/MASH treatment.

CRUDE INULIN DERIVED FROM DAHLIA TUBER AS NANOMATERIAL AND ITS CHARACTERIZATION

Objective: Dahlia tuber (Dahlia sp.) is one of the inulin sources that could be planted in Indonesia. Inulin is fructan-based polysaccharide. Therefore, the research aimed to investigate inulin from the extract of dahlia tuber as a drug excipient, especially for nanoparticles based on inulin-cysteamine thiomer. Methods: Crude inulin was isolated from dahlia tuber using ethanol for maceration. The resulting inulin was characterized using FT-IR and oxidized using sodium periodate (NaIO4) to increase solubility. Afterward, the oxidized crude inulin was further modified by conjugation with cysteamine to produce a cationic thiomer using reductive amination. The thiomer was evaluated regarding the number of thiol groups and solubility. The nanoparticles were prepared using ionic gelation methods. The resulting nanoparticles were evaluated for particle size and zeta potential. Results: Inulin can be isolated from dahlia tuber with its content of 18.60±4.45% and carbohydrate of 61.75±0.75%. Crude inulin can be conjugated with cysteamine to generate a cationic thiomer using NaCNBH3 as a reductant, which can increase its solubility with free thiol group content of 415.21±40.39 µmol/g. Nanoparticles were generated from crude inulin-cysteamine thiomer with sodium tripolyphosphate (NaTTP), leading to a particle size of 180 nm and zeta potential of-10.8 mV. Conclusion: As a potential nanoparticulate drug delivery system, a cationic thiomer could be synthesized from inulin derived from dahlia tuber grown in Indonesia.

Application of quality by design in optimization of nanoformulations: Principle, perspectives and practices.

Nanoparticulate drug delivery systems (NDDS) based nanoformulations have emerged as promising drug delivery systems. Various NDDS-based formulations have been reported such as polymeric nanoparticles (NPs), nanoliposomes, solid lipid NPs, nanocapsules, liposomes, self-nano emulsifying drug delivery systems, pro liposomes, nanospheres, microemulsion, nanoemulsion, gold NPs, silver NPs and nanostructured lipid carrier. They have shown numerous advantages such as enhanced bioavailability, aqueous solubility, permeability, controlled release profile, and blood-brain barrier (BBB) permeability. This advantage of NDDS can help to deliver pure drugs to the target site. However, the formulation of nanoparticles is a complex process that requires optimization to ensure product quality and efficacy. Quality by Design (QbD) is a systemic approach that has been implemented in the pharmaceutical industry to improve the quality and reliability of drug products. QbD involves the optimization of different parameters like zeta potential (ZP), particle size (PS), entrapment efficiency (EE), polydispersity index (PDI), and drug release using statistical experimental design. The present article discussed the detailed role of QbD in optimizing nanoformulations and their advantages, advancement, and applications from the industrial perspective. Various case studies of QbD in the optimization of nanoformulations are also discussed.

Development of modular polymeric nanoparticles for drug delivery using amine reactive chemistry.

Curcumin has been explored for its anti-cancer potential, but is severely limited by its hydrophobicity and sensitivity to light and water. In this study, poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were synthesized to encapsulate curcumin via single emulsion method to improve curcumin stability and bioavailability. The PLGA NPs were coated with oligomeric chitosan (COS) and RGD peptide (a peptide consisting of Arg-Gly-Asp) using amine-reactive chemistry (NHS and EDC). Both COS and RGD had been previously shown to accumulate and target many different types of cancer cells. NPs were characterised based on size distribution, zeta potential, and binding efficiency of RGD peptide. They were also evaluated on encapsulation efficiency, and stability, of curcumin within the NPs. OVCAR-3 cancer cells were treated with COS and RGD-coated PLGA NPs loaded with Coumarin-6 dye for fluorescent imaging of cell uptake. They were also treated with curcumin-loaded NPs to determine cytotoxicity and effectiveness of delivery. The NPs exhibited size distribution and zeta potential within expected values, though binding efficiency of RGD was low. Curcumin-loaded NPs showed significant increase in cytotoxicity over free (unencapsulated) curcumin, and void (empty) NPs, suggesting successful delivery of curcumin as an anti-cancer agent; the performance of COS and RGD coated NPs over bare PLGA NPs was inconclusive, however, optimization will be required to improve formulation during the coating steps. This method of NP synthesis serves as proof of concept for a modular solution to the development of various coated polymeric NPs for other drugs or applications.

Folate Receptor β (FRβ) Expression on Myeloid Cells and the Impact of Reticuloendothelial System on Folate-Functionalized Nanoparticles' Biodistribution in Cancer.

Folate uptake is largely mediated by folate receptor (FR)β, encoded by FOLR2 gene, in myeloid immune cells such as granulocytes, monocytes, and especially in macrophages that constitute the reticuloendothelial system (RES) and infiltrate the tumor microenvironment. Since the myeloid immune compartment dynamically changes during tumorigenesis, it is critical to assess the infiltration status of the tumors by FRβ-expressing myeloid cells to better define the targeting efficacy of folate-functionalized drug delivery systems. On the other hand, clearance by RES is a major limitation for the targeting efficacy of nanoparticles decorated with folate. Therefore, the aims of this study are (i) to determine the amount and subtypes of FRβ+ myeloid cells infiltrating the tumors at different stages, (ii) to compare the amount and subtype of FRβ+ myeloid cells in distinct organs of tumor-bearing and healthy animals, (iii) to test if the cancer-targeting efficacy and biodistribution of a prototypic folate-functionalized nanoparticle associates with the density of FRβ+ myeloid cells. Here, we report that myeloid cell infiltration was enhanced and FRβ was upregulated at distinct stages of tumorigenesis in a mouse breast cancer model. The CD206+ subset of macrophages highly expressed FRβ, prominently both in tumor-bearing and healthy mice. In tumor-bearing mice, the amount of all myeloid cells, but particularly granulocytes, was remarkably increased in the tumor, liver, lungs, spleen, kidneys, lymph nodes, peritoneal cavity, bone marrow, heart, and brain. Compared with macrophages, the level of FRβ was moderate in granulocytes and monocytes. The density of FRβ+ immune cells in the tumor microenvironment was not directly associated with the tumor-targeting efficacy of the folate-functionalized cyclodextrin nanoparticles. The lung was determined as a preferential site of accumulation for folate-functionalized nanoparticles, wherein FRβ+CD206+ macrophages significantly engulfed cyclodextrin nanoparticles. In conclusion, our results demonstrate that the tumor formation augments the FR levels and alters the infiltration and distribution of myeloid immune cells in all organs which should be considered as a major factor influencing the targeting efficacy of nanoparticles for drug delivery.

Current Overview on the Use of Nanosized Drug Delivery Systems in the Treatment of Neurodegenerative Diseases.

Neurodegenerative diseases, encompassing conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, prion disease, and Huntington's disease, present a growing health concern as human life expectancy increases. Despite this, effective treatments to halt disease progression remain elusive due to various factors, including challenges in drug delivery across physiological barriers like the blood-brain barrier and patient compliance issues leading to treatment discontinuation. In response, innovative treatment approaches leveraging noninvasive techniques with higher patient compliance are emerging as promising alternatives. This Review aims to synthesize current treatment options and the challenges encountered in managing neurodegenerative diseases, while also exploring innovative treatment modalities. Specifically, noninvasive strategies such as intranasal administration and nanosized drug delivery systems are gaining prominence for their potential to enhance treatment efficacy and patient adherence. Nanosized drug delivery systems, including liposomes, polymeric micelles, and nanoparticles, are evaluated within the context of outstanding studies. The advantages and disadvantages of these approaches are discussed, providing insights into their therapeutic potential and limitations. Through this comprehensive examination, this Review contributes to the ongoing discourse surrounding the development of effective treatments for neurodegenerative diseases.

Amino-functionalised mesoporous silica nanoparticles for the delivery of isoniazid and its metal complexes

The effective delivery of poor water-soluble anti-tubercular drugs such as isoniazid to their target sites is a major factor that has made it difficult for tuberculosis to be eradicated. Isoniazid derivatives and nano-particulate drug delivery systems are explored as one way to address this limitation. This study investigated the use of amino-functionalised mesoporous silica nanoparticles (MCM-41) as nano-carriers for the delivery of isoniazid-based metal complexes, Cu–INH and Fe–INH. The Sol-gel method was used to synthesise the nano-carriers, which produced a series of well-ordered nano-carriers. Their physicochemical properties were modified through surface functionalisation with amino groups via post-grafting synthesis. The isoniazid-based metal complexes were incorporated into the nano-carriers using rotary evaporation. The nano-carriers were characterised using X-ray diffraction (XRD), Zeta potential, Fourier Transmission Infra-red (FT-IR), Brunaeur Emmett Teller (BET), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM) and Thermogravimetric analysis (TGA). These characterisation techniques confirmed the successful surface functionalisation of the nano-carriers with amino groups and their encapsulation with INH, Cu–INH and Fe–INH. The amino-functionalised nano-carriers were observed to have the highest drug loading capacities and entrapment efficiencies within the range of 7.85%–19.31 % and 39.26%–96.53 %, respectively. The release rates of INH, Cu–INH, and Fe–INH from the nano-carriers were also studied in Phosphate Buffer Solution (PBS) with pH of 7.4 and 5.4 using ultraviolet–visible spectroscopy. The cumulative release rates of INH, Cu–INH, and Fe–INH from their nano-carriers depended on their release media's textural properties and environmental conditions. Amino functionalised nano-carriers had high release rates, with A-MCM-41+Cu–INH having the highest of 37.09 % in PBS at 5.4 after 24 h. The cumulative data obtained was fitted into Zero order, First order, Hixson Crowell, Higuchi, Korsmeyer-Peppas and Weibull models. The Hixson Crowell, Korsmeyer-Peppas, and Weibull models fitted well with correlation coefficients (R2) of 0.9813, 0.9769 and 0.9802, respectively, for MCM-41+INH in PBS of pH 5.4.

Reduced nephrotoxicity of epichlorohydrin-crosslinked β-cyclodextrin nanoparticles (βCDNPs) and its enhanced binding with hydrophobic compounds

This paper explores the development and characterization of epichlorohydrin-crosslinked β-cyclodextrin nanoparticles (βCDNPs) for drug delivery, focusing on their interaction with hydrophobic drugs and biocompatibility. We synthesized βCDNPs using β-cyclodextrin (βCD) and epichlorohydrin (ECH). Our study assessed the biocompatibility and safety of βCDNPs, particularly in avoiding nephrotoxicity commonly associated with βCD, by examining their interaction with cholesterol and conducting survival analyses in mice at various dosing concentrations. Additionally, we highlight the advantages of using diffusion-ordered NMR spectroscopy (DOSY) to determine the enhanced binding constants of βCDNPs with hydrophobic compounds, in comparison with the solubility method, Job plot analysis, and isothermal titration calorimetry (ITC). We demonstrated the enhanced binding capacity of βCDNPs compared to βCD alone and established the polymerization of βCD as a significant factor in this enhancement. Our findings suggest that βCDNPs show promise as drug delivery systems due to their improved solubility, stability, and safety profiles.

Delivery Strategy to Enhance the Therapeutic Efficacy of Liver Fibrosis via Nanoparticle Drug Delivery Systems.

Liver fibrosis (LF) is a pathological repair reaction caused by a chronic liver injury that affects the health of millions of people worldwide, progressing to life-threatening cirrhosis and liver cancer without timely intervention. Due to the complexity of LF pathology, multiple etiological characteristics, and the deposited extracellular matrix, traditional drugs cannot reach appropriate targets in a time-space matching way, thus decreasing the therapeutic effect. Nanoparticle drug delivery systems (NDDS) enable multidrug co-therapy and develop multifactor delivery strategies targeting pathological processes, showing great potential in LF therapy. Based on the pathogenesis and the current clinical treatment status of LF, we systematically elucidate the targeting mechanism of NDDS used in the treatment of LF. Subsequently, we focus on the progress of drug delivery applications for LF, including combined delivery for the liver fibrotic pathological environment, overcoming biological barriers, precise intracellular regulation, and intelligent responsive delivery for the liver fibrotic microenvironment. We hope that this review will inspire the rational design of NDDS for LF in the future in order to provide ideas and methods for promoting LF regression and cure.

Small Particles, Big Potential: Polymeric Nanoparticles for Drug Delivery in Parkinson's Disease.

Despite the availability of a number of efficacious treatments for Parkinson's disease, their limitations and drawbacks, particularly related to low brain bioavailability and associated side effects, emphasize the need for alternative and more effective therapeutic approaches. Nanomedicine, the application of nanotechnology in medicine, has received considerable interest in recent years as a method of effectively delivering potentially therapeutic molecules to the brain. In particular, polymeric nanoparticles, constructed from biodegradable polymer, have shown great promise in enhancing therapeutic efficacy, reducing toxicity, and ensuring targeted delivery. However, their clinical translation remains a considerable challenge. This article reviews recent in vitro and in vivo studies using polymeric nanoparticles as drug and gene delivery systems for Parkinson's disease with their challenges and future directions. We are also particularly interested in the technical properties, mechanism, drugs release patterns, and delivery strategies to overcome the blood-brain barrier. © 2024 International Parkinson and Movement Disorder Society.

Multifunctional Sr,Mg-Doped Mesoporous Bioactive Glass Nanoparticles for Simultaneous Bone Regeneration and Drug Delivery.

Mesoporous bioactive glass nanoparticles (MBGNs) doped with therapeutical ions present multifunctional systems that enable a synergistic outcome through the dual delivery of drugs and ions. The aim of this study was to evaluate influence of co-doping with strontium and magnesium ions (SrMg-MBGNs) on the properties of MBGNs. A modified microemulsion-assisted sol-gel synthesis was used to obtain particles, and their physicochemical properties, bioactivity, and drug-loading/release ability were evaluated. Indirect biological assays using 2D and 3D cell culture models on human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and endothelial EA.hy926 cells, respectively, were used to determine biocompatibility of MBGNs, their influence on alkaline phosphatase (ALP) production, calcium deposition, and cytoskeletal organization. Results showed that Sr,Mg-doping increased pore volume and solubility, and changed the mesoporous structure from worm-like to radial-dendritic, which led to a slightly accelerated drug release compared to pristine MBGNs. Biological assays confirmed that particles are biocompatible, and have ability to slightly induce ALP production and calcium deposition of hBM-MSCs, as well as to significantly improve the proliferation of EA.hy926 compared to biochemical stimulation via vascular endothelial growth factor (VEGF) administration or regular media. Fluorescence staining revealed that SrMg-MBGNs had a similar effect on EA.hy926 cytoskeletal organization to the VEGF group. In conclusion, Sr,Mg-MBGNs might be considered promising biomaterial for biomedical applications.

Diselenide-Bridged Mesoporous Silica-Based Nanoplatform with a Triple ROS-Scavenging Effect for Intracerebral Hemorrhage Treatment.

Oxidative stress (OS) is a major mediator of secondary brain injury following intracerebral hemorrhage (ICH). Thus, antioxidant therapy is emerging as an attractive strategy to combat ICH. To achieve both reactive oxygen species (ROS) scavenging ability and on-demand drug release ability, we constructed a novel polydopamine (PDA)-coated diselenide-bridged mesoporous silica nanoparticle (DSeMSN) drug delivery system (PDA-DSeMSN). Edaravone (Eda) was blocked in the pores of DSeMSN by covering the pores with PDA as a gatekeeper. The drug maintained nearly "zero release" before reaching the lesion site, while in the ROS-enriched circumstances, the PDA shell went through degradation and the doped diselenide bonds broke up, triggering the disintegration of nanoparticles and leading to Eda release. Interestingly, the ROS-degradable property of the PDA shell and diselenide bond endowed the system with enhanced ROS-eliminating capacity. The synergistic effect of ROS-responsive drug delivery and ROS-scavenging PDA-DSeMSN showed efficient antioxidative and mitochondria protective performance without apparent toxicity in vitro. Importantly, PDA-DSeMSN@Eda through intravenous administration specifically accumulated in perihematomal sites and demonstrated robust neuroprotection in an ICH mouse model through antioxidative and antiapoptotic effects with high biological safety. Thus, the PDA-DSeMSN platform holds tremendous potential as an excellent carrier for on-demand delivery of drugs and provides a new and effective strategy for the clinical treatment of ICH.

Reduction-Responsive Polyprodrug Nanoplatform Based on Curcumin for Tumor-Targeted Therapy.

Polymer prodrug nanoparticles have become an emerging drug delivery system in cancer therapy due to their high drug loading. However, their poor drug release and lack of tumor cell targeting limit their clinical application. This study aimed to prepare targeted and reduction-reactive polyprodrug nanocarriers based on curcumin (CUR) for co-delivery of doxorubicin (DOX), labeled as DOX/HAPCS NPs, and to investigate their anticancer activity. The polymer was synthesized and characterized by chemical method. The drug loading and drug release behavior of DOX and CUR in polymer nanoparticles were determined. Moreover, the antitumor effects of polymer nanoparticles were evaluated using an MTT experiment and tumor inhibition experiment, and the synergistic effect of co-delivered DOX and CUR was explored. The particle size of DOX/HAPCS NPs was 152.5nm, and the potential was about -26.74 mV. The drug-carrying capacity of DOX and CUR was about 7.56% and 34.75%, respectively, indicating high drug-carrying capacity and good stability. DOX and CUR released over 90% within 24 hours in the tumor environment. Compared with free DOX, DOX/HAPCS NPs demonstrated significantly enhanced cell and tumor inhibitory effects (P< 0.05) in vivo and in vitro and changed drug distribution to avoid toxic side effects on normal tissues. The combined index showed that DOX and CUR showed synergistic anticancer effects at a set ratio. The prepared reduction-responsive targeted polymer nanomedical DOX/HAPCS NPs exhibited a synergistic anti-cancer effect, with high drug loading capacity and the ability to release drugs in proportion, making it a promising polymer nanoparticle drug delivery system.

Addressing barriers in diffuse intrinsic pontine glioma: the transformative role of lipid nanoparticulate drug delivery.

The brainstem tumour known as diffuse intrinsic pontine glioma (DIPG), also known as pontine glioma, infiltrative brainstem glioma is uncommon and virtually always affects children. A pontine glioma develops in the brainstem's most vulnerable region (the "pons"), which regulates a number of vital processes like respiration and blood pressure. It is particularly challenging to treat due to its location and how it invades healthy brain tissue. The hunt for a solution is continually advancing thanks to advances in modern medicine, but the correct approach is still elusive. With a particular focus on brain tumours that are incurable or recur, research is ongoing to discover fresh, practical approaches to target particular areas of the brain. To successfully complete this task, a thorough literature search was carried out in reputable databases like Google Scholar, PubMed, and ScienceDirect. The present article provides a comprehensive analysis of the notable advantages of lipid nanoparticles compared to alternative nanoparticle formulations. The article delves into the intricate realm of diverse lipid-based nanoparticulate delivery systems, which are used in Diffuse Intrinsic Pontine Glioma (DIPG) which thoroughly examines preclinical and clinical studies, providing a comprehensive analysis of the effectiveness and potential of lipid nanoparticles in driving therapeutic advancements for DIPG. There is strong clinical data to support the promising method of using lipid-based nanoparticulate drug delivery for brain cancer treatment, which shows improved outcomes.

“Ball-rod” shaped multifunctional magnetic Janus nanoparticles for efficient drug delivery

Magnetic Janus nanoparticles (MJNPs) have attracted extensive attention in the biomedical field due to their asymmetrical composition and independent functional partitioning. In this paper, “ball-rod” shaped drug delivery systems (DDSs) with CoFe2O4 balls and mesoporous silica (mSiO2) rods, which were coated with CDs via imine bonds, were prepared. The DDSs were named CoFe2O4&mSiO2/CDs MJNPs and DOX was used as a model drug to form DOX-CoFe2O4&mSiO2. Capping agent CDs blocked the pore entrance and endowed the carriers with negatively charged surface. CoFe2O4&mSiO2/CDs showed fine magnetic properties and microwave (MW) thermal transition properties contributed to the ball portion of CoFe2O4. The drug release behavior of DOX-CoFe2O4&mSiO2/CDs showed pH/MW dual-responsiveness. The broken of imine bonds resulted in the detachment of CDs and the NPs became positively charged. The new NPs provided new insights for designing multi-functional DDSs.

Ocimum basilicum and Lagenaria siceraria Loaded Lignin Nanoparticles as Versatile Antioxidant, Immune Modulatory, Anti-Efflux, and Antimicrobial Agents for Combating Multidrug-Resistant Bacteria and Fungi.

Lignin nanoparticles emerged as a promising alternative for drug delivery systems owing to their biodegradability and bioactive properties. This study investigated the antimicrobial activity of the ethanolic extract of Ocimum basilicum-loaded lignin nanoparticles (OB-LNPs) and Lagenaria siceraria seed oil-loaded lignin nanoparticles (LS-LNPs) to find a solution for antimicrobial resistance. OB-LNPs and LS-LNPs were tested for their antimicrobial potential against Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Staphylococcus aureus, Salmonella enterica, Trichophyton mentagrophytes, Trichophyton rubrum, and Microsporum canis. OB-LNPs and LS-LNPs were further tested for their anti-efflux activity against ciprofloxacin-resistant Salmonella enterica strains and for treating Salmonella infection in a rat model. We also investigated the antifungal efficacy of OB-LNPs and LS-LNPs for treating T. rubrum infection in a guinea pig model. Both OB-LNPs and LS-LNPs showed strong antimicrobial potential against S. Typhimurium and T. rubrum infections. LS-LNPs showed antibacterial activity against Salmonella enterica species with a MIC range of 0.5-4 µg/mL and antifungal activity against T. rubrum with a MIC range of 0.125-1 µg/mL. OB-LNPs showed antibacterial activity against Salmonella enterica species with a MIC range of 0.5-2 µg/mL and antifungal activity against T. rubrum with a MIC range of 0.25-2 µg/mL. OB-LNPs and LS-LNPs downregulated the expression of ramA and acrB efflux pump genes (fold change values ranged from 0.2989 to 0.5434; 0.4601 to 0.4730 for ramA and 0.3842-0.6199; 0.5035-0.8351 for acrB). Oral administration of OB-LNPs and LS-LNPs in combination with ciprofloxacin had a significant effect on all blood parameters, as well as on liver and kidney function parameters. Oxidative stress mediators, total antioxidant capacity, and malondialdehyde were abolished by oral administration of OB-LNPs and LS-LNPs (0.5 mL/rat once daily for 5 days). Interferon-γ and tumor necrosis factor-α were also reduced in comparison with the positive control group and the ciprofloxacin-treated group. Histopathological examination of the liver and intestine of OB-LNPs and LS-LNPs-treated rats revealed an elevation in Salmonella clearance. Treatment of T. rubrum-infected guinea pigs with OB-LNPs and LS-LNPs topically in combination with itraconazole resulted in a reduction in lesion scores, microscopy, and culture results. In conclusion, OB-LNPs and LS-LNPs possess immunomodulatory and antioxidant potential and can be used as naturally derived nanoparticles for drug delivery and treatment of Salmonellosis and dermatophytosis infections.

Cell Membrane-Derived Nanoparticles as Biomimetic Nanotherapeutics to Alleviate Fatty Liver Disease.

The prevalence of metabolic dysfunction associated-steatotic liver disease (MASLD) (formerly known as nonalcoholic fatty liver disease; NAFLD) is estimated at around 32% of the world's population, resulting in a major healthcare concern in recent times. Current pharmaceutical methods lack efficacy for the treatment of the disease because of suboptimal pharmacokinetic parameters including poor bioavailability, short half-life, and premature clearance. Designing an efficient drug delivery system that provides a protective environment is critical for addressing these challenges. Such a system should aim to enhance the cellular uptake of drugs, improve their bioavailability, and reduce the chances of rapid clearance. Here, we developed nanoengineered natural cell membrane-derived nanoparticles (CMNs) incorporated with a model drug, rosuvastatin, in the bilayer assembly of CMNs to reduce the accumulation of lipids in hepatocytes, a hallmark of MASLD. We used a cell extrusion technique to develop self-assembled CMNs with precise size control compared to the cell shearing method. Interestingly, the prepared CMNs were found to be nonphagocytic, representing around 1.13% of phosphatidylserine receptors on healthy cells, which allows the possibility of their use as stealth nanoparticles for drug delivery. Furthermore, CMNs exhibit higher drug-loading efficiency, excellent cytocompatibility, and enhanced cellular internalization capabilities. Moreover, we show that the delivery of rosuvastatin-loaded CMNs in the in vitro MASLD model efficiently reduced hepatocyte lipid accumulation, including total cholesterol (26.8 ± 3.1%) and triglycerides (11.8 ± 0.8%), compared to the negative control. Taken together, the nanoengineered biomimetic CMNs enhance the drug's bioactivity in hepatic cells, establishing a foundation for further investigation of this drug delivery system in treating MASLD.