Approach For Targeted Delivery Research Articles

Drug Delivery System Approaches for Rheumatoid Arthritis Treatment: A Review.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that has traditionally been treated using a variety of pharmacological compounds. However, the effectiveness of these treatments is often limited due to challenges associated with their administration. Oral and parenteral routes of drug delivery are often restricted due to issues such as low bioavailability, rapid metabolism, poor absorption, first-pass effect, and severe side effects. In recent years, nanocarrier-based delivery methods have emerged as a promising alternative for overcoming these challenges. Nanocarriers, including nanoparticles, dendrimers, micelles, nanoemulsions, and stimuli-sensitive carriers, possess unique properties that enable efficient drug delivery and targeted therapy. Using nanocarriers makes it possible to circumvent traditional administration routes' limitations. One of the key advantages of nanocarrier- based delivery is the ability to overcome resistance or intolerance to traditional antirheumatic therapies. Moreover, nanocarriers offer improved drug stability, controlled release kinetics, and enhanced solubility, optimizing the therapeutic effect. They can also protect the encapsulated drug, prolonging its circulation time and facilitating sustained release at the target site. This targeted delivery approach ensures a higher concentration of the therapeutic agent at the site of inflammation, leading to improved therapeutic outcomes. This article explores potential developments in nanotherapeutic regimens for RA while providing a comprehensive summary of current approaches based on novel drug delivery systems. In conclusion, nanocarrier-based drug delivery systems have emerged as a promising solution for improving the treatment of rheumatoid arthritis. Further advancements in nanotechnology hold promise for enhancing the efficacy and safety of RA therapies, offering new hope for patients suffering from this debilitating disease.

Metal-Based Drugs in Cancer Therapy

Metal-based drugs have emerged as pivotal therapeutics in cancer therapy, enlightening a path toward innovative and effective treatment strategies. Platinum-based therapeutics, notably cisplatin, carboplatin, and oxaliplatin, have transformed the landscape of cancer treatment, setting the stage for the development of next-generation metal-based compounds. Delving into the principles governing the design of metal-based drugs, this article navigates through their intricate coordination chemistry, targeted delivery approaches, and mechanisms of action. Notably, metal-based compounds form covalent bonds with DNA, disrupting vital cellular processes and inducing apoptosis in cancerous tissues. Even though contemporary chemotherapy as well as radiotherapeutic methods have greatly increased patient survival rates, disease recurrence still represents a fatal danger. The probability of metastasis and the drug resistance are increased by the incomplete clearance of neoplastic tissues from the body. This review explores the compelling journey of metal-based compounds, from their historical significance in ancient remedies to their pivotal role in modern oncology, and also discusses the recent advancements and emerging trends that promise to shape the future of metallodrugs. The shining promise of metal-based drugs in cancer remedies holds the potential to revolutionize treatment paradigms, offering hope and resilience in the ongoing battle against one of humanity's most relentless adversaries.

Neutrophil elastase as a versatile cleavage enzyme for activation of αvβ3 integrin-targeted small molecule drug conjugates with different payload classes in the tumor microenvironment.

Introduction: The development of bioconjugates for the targeted delivery of anticancer agents is gaining momentum after recent success of antibody drug conjugates (ADCs) in the clinic. Smaller format conjugates may have several advantages including better tumor penetration; however, cellular uptake and trafficking may be substantially different from ADCs. To fully leverage the potential of small molecule drug conjugates (SMDCs) with potent binding molecules mediating tumor homing, novel linker chemistries susceptible for efficient extracellular activation and payload release in the tumor microenvironment (TME) need to be explored. Methods: We designed a novel class of SMDCs, which target αvβ3 integrins for tumor homing and are cleaved by neutrophil elastase (NE), a serine protease active in the TME. A peptidomimetic αvβ3 ligand was attached via optimized linkers composed of substrate peptide sequences of NE connected to different functional groups of various payload classes, such as camptothecins, monomethyl auristatin E, kinesin spindle protein inhibitors (KSPi) and cyclin-dependent kinase 9 inhibitors (CDK-9i). Results: NE-mediated cleavage was found compatible with the diverse linker attachments via hindered ester bonds, amide bonds and sulfoximide bonds. Efficient and traceless release of the respective payloads was demonstrated in biochemical assays. The newly designed SMDCs were highly stable in buffer as well as in rat and human plasma. Cytotoxicity of the SMDCs in cancer cell lines was clearly dependent on NE. IC50 values were in the nanomolar or sub-nanomolar range across several cancer cell lines reaching similar potencies as compared to the respective payloads only in the presence of NE. In vivo pharmacokinetics evaluating SMDC and free payload exposures in rat and particularly the robust efficacy with good tolerability in triple negative breast and small cell lung cancer murine models demonstrate the utility of this approach for selective delivery of payloads to the tumor. Discussion: These results highlight the broad scope of potential payloads and suitable conjugation chemistries paving the way for future SMDCs harnessing the safety features of targeted delivery approaches in combination with NE cleavage in the TME.

Self-assembly of maltose-albumin nanoparticles for efficient targeting delivery and therapy in liver cancer

The effective delivery and targeted release of drugs within tumor cells are critical factors in determining the therapeutic efficacy of nanomedicine. To achieve this objective, a conjugate of maltose (Mal) and bovine serum albumin (BSA) was synthesized by the Maillard reaction and self-assembled into nanoparticles with active-targeting capabilities upon pH/heating induction. This nanoparticle could be effectively loaded with doxorubicin (DOX) to form stable nanodrugs (Mal-BSA/DOX) that were sensitive to low pH or high glutathione (GSH), thereby achieving a rapid drug release (96.82 % within 24 h). In vitro cell experiments indicated that maltose-modified BSA particles efficiently enhance cellular internalization via glucose transporters (GLUT)-mediated endocytosis, resulting in increased intracellular DOX levels and heightened expression of γ-H2AX. Consequently, these results ultimately lead to selective tumor cells death, as evidenced by an IC50 value of 3.83 μg/mL in HepG2 cells compared to 5.87 μg/mL in 293t cells. The efficacy of Mal-BSA/DOX in tumor targeting therapy has been further confirmed by in vivo studies, as it effectively delivered a higher concentration of DOX to tumor tissue. This targeted delivery approach not only reduces the systemic toxicity of DOX but also effectively inhibits tumor growth (TGI, 75.95 %). These findings contribute valuable insights into the advancement of targeting-albumin nanomedicine and further support its potential in tumor treatment.

Development of NGR-GelMA Hydrogels for PC3 Prostate Cancer Cells

Prostate cancer is one of the most common cancer type for men. Current therapies such as chemotherapy or radiotherapy non-spesifically affect cancerous cells. Current therapies need more targeted delivery approaches such as peptide. Asn-Gly-Arg (NGR) is a tool for cancer targeting therapy. To mimic more natural cancer microenvironment, peptide treatment approaches are examined in 3 Dimensional (D) hydrogels. GelMA is one of the hydrogels that permits to construct 3D microenvironment of PC3 prostate cancer cells. The goal of the study was to evaluate characteristic of GelMA to model prostate cancer environment and to determine the effects of NGR peptides for PC3 line. Measurement of pH values of GelMA in different NGR peptide concentration were conducted (1 µM, 10 µM and 100 µM) were measured. To analyze biodegradation capacity of GelMA in different NGR peptide concentration, weigth measurements were performed. Live and Dead analysis was performed on days 1, 4, and 7. The experimental findings revealed that GelMA hydrogels created a relatively stable and neutral pH environment, making them potentially valuable for drug delivery systems. Furthermore, the GelMA hydrogels incorporated with NGR exhibited the capacity to absorb liquids, resulting in an increase in weight. Notably, these hydrogels allowed for the observation of the dynamic 3D microenvironment of prostate cancer, which was influenced by the concentration of the targeted drug in the GelMA matrix. This suggests promising implications for developing targeted therapies for prostate cancer using GelMA-based drug delivery systems. As a conclusion, GelMA and GelMA including NGR peptide may be useful platform for further studies to progress on prostate cancer treatment.

Self-Assembled Acid-Responsive Nanosystem for Synergistic Anti-Angiogenic/Photothermal/Ferroptosis Therapy against Esophageal Cancer.

Esophageal cancer (EC) treatment via anti-angiogenic therapy faces challenges due to non-cytotoxicity and non-specific biodistribution of the anti-angiogenic agents. Hence, the quest for a synergistic treatment modality and a targeted delivery approach to effectively address EC has become imperative. In this study, an acid-responsive release nanosystem (Bev-IR820@FeIII TA) that involves the conjugation of bevacizumab, an anti-angiogenic monoclonal antibody, with TA and Fe3+ to form a metal-phenolic network, followed by loading with the near-infrared photothermal agent (IR820) to achieve combinational therapy, is designed. The construction of Bev-IR820@FeIII TA can be realized through a facile self-assembly process. The Bev-IR820@FeIII TA exhibits tumor-targeting capabilities and synergistic therapeutic effects, encompassing anti-angiogenic therapy, photothermal therapy (PTT), and ferroptosis therapy (FT). Bev-IR820@FeIII TA exhibits remarkable proficiency in delivering drugs to EC tissue through its pH-responsive release properties. Consequently, bevacizumab exerts its therapeutic effects by obstructing tumor angiogenesis, thereby impeding tumor growth. Meanwhile, PTT facilitates localized thermal ablation at the tumor site, directly eradicating EC cells. FT synergistically collaborates with PTT, giving rise to the formation of a reactive oxygen species (ROS) storm, subsequently culminating in the demise of EC cells. In summary, this amalgamated treatment modality carries substantial promise for synergistically impeding EC progression and showcases auspicious prospects for future EC treatment.

Targeted drug delivery approaches for the management of tumors

The treatment of tumors requires specific and selective drug delivery approaches capable of efficiently eliminating the root cause of oncogenesis. In this context, targeted drug delivery strategies are the preferred choice due to their exceptional recognition of tumor cell biology and their high transfection efficacy within the tumor microenvironment. The emergence of nanoscale techniques has marked significant milestones in the successful management of various types of tumors. The development of targeted delivery approaches for tumor therapeutics has gained momentum over the past few decades. However, in contrast to the plethora of successful pre-clinical studies, only a limited number of passively targeted nanocarriers have been approved for clinical use, and none of the actively targeted nanocarriers have advanced beyond clinical trials. This review delves into the major molecular principles associated with tumorigenesis, including active targeting, passive targeting, and cell-mediated targeting. It also explores the biological barriers (systemic, biological, and cellular) encountered in tumor drug delivery. Moreover, the review examines various tumor-targeted drug delivery systems that have been developed over the past decade. These systems encompass polymeric nanoparticles (micelles, nanoparticles, dendrimers, and polyplexes), lipid-based carriers (solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsion), vesicular systems (liposomes, niosomes, aquasomes, and phytosomes), and inorganic nanocarriers (iron oxide nanoparticles, quantum dots, carbon-based nanoparticles, and mesoporous silica nanoparticles), all designed for the alleviation of tumors.

DNA vaccine incorporated poly (lactic-co-glycolic) acid (PLGA) microspheres offer enhanced protection against Aeromonas hydrophila infection

Encapsulation of DNA vaccines onto carriers enhances the immunogenicity of an antigen. Specifically, biodegradable polymers offer sustained release of vaccines which is crucial for any targeted delivery approach. Poly (lactic-co-glycolic) acid (PLGA) microspheres were used to load a DNA vaccine having a targeted gene of outer membrane protein (OMP) of Aeromonas hydrophila to clone and construct a DNA vaccine using a eukaryotic expression vector system (pVAX1-OMP DNA) and delivery in Carassius auratus against A. hydrophila infection. PLGA microspheres were prepared by emulsion technique oil-in-water and characterized by a High-Resolution Scanning Electron Microscope (HR-SEM). The results of PLGA-pVAX1-OMP DNA microspheres shows that average of 100–150 μm particle size and a loading efficiency (LE) of 68.8 %. Results indicate that C. auratus fed with PLGA-pVAX1-OMP DNA microspheres revealed a significant improvement in innate immune response, which includes, myeloperoxidase activity, respiratory burst and total immunoglobulin level compared with control group fish. The immune-related gene, IL1β, IL10, TGF, c-type, and g-type lysozyme also showed significantly higher expression after immunization. Furthermore, dietary supplementation of the PLGA-pVAX1-OMP DNA (G III) group exhibited a significantly higher survival rate (78 %) than the control group of fish. These results help us to understand the of mechanism of DNA vaccine administrated feed through PLGA nanoparticles resistance to infection by regulating systemic and innate immunity in Carassius auratus.

Nanovaccines to Combat Aeromonas hydrophila Infections in Warm-Water Aquaculture: Opportunities and Challenges.

The application of nanotechnology in aquaculture for developing efficient vaccines has shown great potential in recent years. Nanovaccination, which involves encapsulating antigens of fish pathogens in various polymeric materials and nanoparticles, can afford protection to the antigens and a sustained release of the molecule. Oral administration of nanoparticles would be a convenient and cost-effective method for delivering vaccines in aquaculture while eliminating the need for stressful, labour-intensive injectables. The small size of nanoparticles allows them to overcome the degradative digestive enzymes and help deliver antigens to the target site of the fish more effectively. This targeted-delivery approach would help trigger cellular and humoral immune responses more efficiently, thereby enhancing the protective efficacy of vaccines. This is particularly relevant for combating diseases caused by pathogens like Aeromonas hydrophila, a major fish pathogen responsible for significant morbidity and mortality in the aquaculture sector. While the use of nanoparticle-based vaccines in aquaculture has shown promise, concerns exist about the potential toxicity associated with certain types of nanoparticles. Some nanoparticles have been found to exhibit varying degrees of toxicity, and their safety profiles need to be thoroughly assessed before widespread application. The introduction of nanovaccines has opened new vistas for improving aquaculture healthcare, but must be evaluated for potential toxicity before aquaculture applications. Details of nanovaccines and their mode of action, with a focus on protecting fish from infections and outbreaks caused by the ubiquitous opportunistic pathogen A. hydrophila, are reviewed here.

Therapeutic potential of GDNF in neuroinflammation: Targeted delivery approaches for precision treatment in neurological diseases

Therapeutic potential of GDNF in neuroinflammation: Targeted delivery approaches for precision treatment in neurological diseases

Preclinical Assessment of ADAM9-Responsive Mesoporous Silica Nanoparticles for the Treatment of Pancreatic Cancer.

Pancreatic adenocarcinoma (PDAC) remains largely refractory to chemotherapeutic treatment regimens and, consequently, has the worst survival rate of all cancers. The low efficacy of current treatments results largely from toxicity-dependent dose limitations and premature cessation of therapy. Recently, targeted delivery approaches that may reduce off-target toxicities have been developed. In this paper, we present a preclinical evaluation of a PDAC-specific drug delivery system based on mesoporous silica nanoparticles (MSNs) functionalized with a protease linker that is specifically cleaved by PDAC cells. Our previous work demonstrated that ADAM9 is a PDAC-enriched protease and that paclitaxel-loaded ADAM9-responsive MSNs effectively kill PDAC cells in vitro. Here, we show that paclitaxel-loaded ADAM9-MSNs result in off-target cytotoxicity in clinically relevant models, which spurred the development of optimized ADAM9-responsive MSNs (OPT-MSNs). We found that these OPT-MSNs still efficiently kill PDAC cells but, as opposed to free paclitaxel, do not induce death in neuronal or bone marrow cells. In line with these in vitro data, paclitaxel-loaded OPT-MSNs showed reduced organ damage and leukopenia in a preclinical PDAC xenograft model. However, no antitumor response was observed upon OPT-MSN administration in vivo. The poor in vivo antitumor activity of OPT-MSNs despite efficient antitumor effects in vitro highlights that although MSN-based tumor-targeting strategies may hold therapeutic potential, clinical translation does not seem as straightforward as anticipated.

Current Status and Future Prospects of Hydrogen Sulfide Donor‐Based Delivery Systems

AbstractNowadays, hydrogen sulfide (H2S) is regarded as an endogenous gaseous signaling molecule in mammals. As a gas transmitter, it induces important biological effects in many physiological and pathological processes, and possesses great therapeutic potentials. However, this bioactive gas has concentration‐related toxicity, rapid evaporation, and high reactivity, making it inconvenient to use as a therapeutic agent. As an exogenous source of H2S, various H2S donors are developed to release H2S after triggering the response under specific conditions, so as to supplement the level of H2S in the body. Meanwhile, to enhance the therapeutic efficacy and reduce the possible toxicities of the H2S donors, various new materials or methods for H2S delivery are studied, realizing sustained/controlled release profiles as well as achieving triggered, long‐term, local or targeted delivery approaches for the gas. This review summarizes the representative H2S donors and the latest progress of hydrogen sulfide donor‐based delivery systems, and the applications of such delivery systems in a series of target diseases that are suitable and expected to be treated by H2S, in order to provide reference for the design of secure and efficient H2S donor drug delivery system. In addition, the future of this field is also prospected.

Harnessing immunotherapy to enhance the systemic anti-tumor effects of thermosensitive liposomes.

Chemotherapy plays an important role in debulking tumors in advance of surgery and/or radiotherapy, tackling residual disease, and treating metastatic disease. In recent years many promising advanced drug delivery strategies have emerged that offer more targeted delivery approaches to chemotherapy treatment. For example, thermosensitive liposome-mediated drug delivery in combination with localized mild hyperthermia can increase local drug concentrations resulting in a reduction in systemic toxicity and an improvement in local disease control. However, the majority of solid tumor-associated deaths are due to metastatic spread. A therapeutic approach focused on a localized target area harbors the risk of overlooking and undertreating potential metastatic spread. Previous studies reported systemic, albeit limited, anti-tumor effects following treatment with thermosensitive liposomal chemotherapy and localized mild hyperthermia. This work explores the systemic treatment capabilities of a thermosensitive liposome formulation of the vinca alkaloid vinorelbine in combination with mild hyperthermia in an immunocompetent murine model of rhabdomyosarcoma. This treatment approach was found to be highly effective at heated, primary tumor sites. However, it demonstrated limited anti-tumor effects in secondary, distant tumors. As a result, the addition of immune checkpoint inhibition therapy was pursued to further enhance the systemic anti-tumor effect of this treatment approach. Once combined with immune checkpoint inhibition therapy, a significant improvement in systemic treatment capability was achieved. We believe this is one of the first studies to demonstrate that a triple combination of thermosensitive liposomes, localized mild hyperthermia, and immune checkpoint inhibition therapy can enhance the systemic treatment capabilities of thermosensitive liposomes.

Docetaxel-loaded borage seed oil nanoemulsion with improved antitumor activity for solid tumor treatment: Formulation development, in vitro, in silico and in vivo evaluation

In the present work, docetaxel-nanoemulsion (DTX-NE) was developed with the aim to improve its therapeutic activity while reducing the side-effects by targeted delivery approach. The unique approach about the developed formulation was use of borage seed oil as the oil phase which has abundant gamma-linolenic acid (GLA) in it and has been previously reported for its anticancer activity. DTX was solubilized in Borage oil and the system was emulsified using Phospholipid (Lipoid E−80). The nanoemulsion was developed by high shear homogenization and ultrasonication. Systematic optimization of critical factors was carried out using Box-Behnken design. The optimized nanoemulsion showed particle size (180.2 ± 4.5 nm), zeta potential (−33.7 ± 1.9 mV) and PDI (0.178 ± 0.01) within the desired limits. The drug entrapment efficiency was found to be 96.41 ± 4.7% while drug loading was found to be 12.87 ± 1.3%. Further, FTIR, DSC and XRD analysis revealed compatibility of the drug with the excipients in addition to complete drug solubilization and entrapment. Further, in vitro release study performed in PBS (pH 7.4) indicated a biphasic profile while release kinetic evaluation showed best fitting as per Korsemeyer-Peppas model with drug release through Fickian diffusion mechanism. In silico docking performed of DTX and GLA suggested excellent binding with microtubule subunit with the binding affinity of −6.4 kcal/mol and −5.7 kcal/mol, respectively. In vivo pharmacokinetic studies in Albino Wistar rats indicated significant improvement in AUC (3.9-folds), t1/2 (2.0-folds) and MRT (4.0-folds) from DTX-NE vis-à-vis the plain drug, respectively. Furthermore, antitumor efficacy of DTX-NE showed significant reduction in the tumor growth (3.17-times) than the free drug and marketed formulation (Taxotere®).

Targeted Carbon Nanostructures for Chemical and Gene Delivery to Plant Chloroplasts.

Nanotechnology approaches for improving the delivery efficiency of chemicals and molecular cargoes in plants through plant biorecognition mechanisms remain relatively unexplored. We developed targeted carbon-based nanomaterials as tools for precise chemical delivery (carbon dots, CDs) and gene delivery platforms (single-walled carbon nanotubes, SWCNTs) to chloroplasts, key organelles involved in efforts to improve plant photosynthesis, assimilation of nutrients, and delivery of agrochemicals. A biorecognition approach of coating the nanomaterials with a rationally designed chloroplast targeting peptide improved the delivery of CDs with molecular baskets (TP-β-CD) for delivery of agrochemicals and of plasmid DNA coated SWCNT (TP-pATV1-SWCNT) from 47% to 70% and from 39% to 57% of chloroplasts in leaves, respectively. Plants treated with TP-β-CD (20 mg/L) and TP-pATV1-SWCNT (2 mg/L) had a low percentage of dead cells, 6% and 8%, respectively, similar to controls without nanoparticles, and no permanent cell and chloroplast membrane damage after 5 days of exposure. However, targeted nanomaterials transiently increased leaf H2O2 (0.3225 μmol gFW-1) above control plant levels (0.03441 μmol gFW-1) but within the normal range reported in land plants. The increase in leaf H2O2 levels was associated with oxidative damage in whole plant cell DNA, a transient effect on chloroplast DNA, and a decrease in leaf chlorophyll content (-17%) and carbon assimilation rates at saturation light levels (-32%) with no impact on photosystem II quantum yield. This work provides targeted delivery approaches for carbon-based nanomaterials mediated by biorecognition and a comprehensive understanding of their impact on plant cell and molecular biology for engineering safer and efficient agrochemical and biomolecule delivery tools.

Dietary Eugenol Nanoemulsion Potentiated Performance of Broiler Chickens: Orchestration of Digestive Enzymes, Intestinal Barrier Functions and Cytokines Related Gene Expression With a Consequence of Attenuating the Severity of E. coli O78 Infection.

Recently, the use of essential oils (EOs) or their bioactive compounds encapsulated by nanoparticles as alternative supplements for in-feed antimicrobials is gaining attention, especially in organic poultry production. Focusing on eugenol, its incorporation into the nanoformulation is a novel strategy to improve its stability and bioavailability and thus augment its growth-boosting and antimicrobial activities. Therefore, we explored eugenol nanoemulsion activities in modulating growth, digestive and gut barrier functions, immunity, cecal microbiota, and broilers response to avian pathogenic E. coli challenge (APEC) O78. A total of 1,000 one-day-old broiler chicks were allocated into five groups; negative control (NC, fed basal diet), positive control (PC), and 100, 250, and 400 mg/kg eugenol nanoemulsion supplemented groups. All groups except NC were challenged with APEC O78 at 14 days of age. The results showed that birds fed eugenol nanoemulsion displayed higher BWG, FI, and survivability and most improved FCR over the whole rearing period. Birds fed 400 mg/kg of eugenol nanoemulsion sustained a higher growth rate (24% vs. PC) after infection. Likely, the expression of digestive enzymes' genes (AMY2A, CCK, CELA1, and PNLIP) was more prominently upregulated and unaffected by APEC O78 challenge in the group fed eugenol nanoemulsion at the level of 400 mg/kg. Enhanced gut barrier integrity was sustained post-challenge in the group supplemented with higher levels of eugenol nanoemulsion as evidenced by the overexpression of cathelicidins-2, β-defensin-1, MUC-2, JAM-2, occludin, CLDN-1, and FABP-2 genes. A distinct modulatory effect of dietary eugenol nanoemulsion was observed on cytokine genes (IL-1β, TNF-α, IL-6, IL-8, and IL-10) expression with a prominent reduction in the excessive inflammatory reactions post-challenge. Supplementing eugenol nanoemulsion increased the relative cecal abundance of Lactobacillus species and reduced Enterobacteriaceae and Bacteriods counts. Notably, a prominent reduction in APEC O78 loads with downregulation of papC, iroN, iutA, and iss virulence genes and detrimental modifications in E. coli morphological features were noticed in the 400 mg/kg eugenol nanoemulsion group at the 3rd-week post-challenge. Collectively, we recommend the use of eugenol nanoemulsion as a prospective targeted delivery approach for achieving maximum broilers growth and protection against APEC O78 infection.

Novel Techniques Targeting Fibroblasts after Ischemic Heart Injury.

The great plasticity of cardiac fibroblasts allows them to respond quickly to myocardial injury and to contribute to the subsequent cardiac remodeling. Being the most abundant cell type (in numbers) in the heart, and a key participant in the several phases of tissue healing, the cardiac fibroblast is an excellent target for treating cardiac diseases. The development of cardiac fibroblast-specific approaches have, however, been difficult due to the lack of cellular specific markers. The development of genetic lineage tracing tools and Cre-recombinant transgenics has led to a huge acceleration in cardiac fibroblast research. Additionally, the use of novel targeted delivery approaches like nanoparticles and modified adenoviruses, has allowed researchers to define the developmental origin of cardiac fibroblasts, elucidate their differentiation pathways, and functional mechanisms in cardiac injury and disease. In this review, we will first characterize the roles of fibroblasts in the different stages of cardiac repair and then examine novel techniques targeting fibroblasts post-ischemic heart injury.

Targeted delivery approaches for synthesis of plant based nanoparticles as anticancer chemotherapeutics

Natural resources, with their immense structural variety, continue to be a vital source of fresh, novel chemical entities with therapeutic usefulness. Current therapy regimens require selective drug targeting to increase action on cancer cells while reducing harm to normal cells. Modified medications and drug delivery systems based on nanotechnology are being developed and launched into the market for better cancer therapy and management, with promising outcomes. This study highlights nanotechnology-based drug delivery vehicles as well as a few targeted delivery methodologies for the manufacture of plant-based nanoparticles that can be further investigated for the creation of more anticancer medications.

Sympathetic Neurostress Drives Osteoblastic Exosomal MiR-21 Transfer to Disrupt Bone Homeostasis and Promote Osteopenia.

Innervation and extracellular vesicle secretion co-exist in the local tissue microenvironment for message transfer, but whether they are interconnected to regulate organ homeostasis remains unknown. Sympatho-adrenergic activation is implicated in stress-induced depression and leads to bone loss, but the mechanisms and therapeutics are incompletely elucidated. Here, it is revealed that sympathetic neurostress through the β1/2 -adrenergic receptor (β1/2-AR) signaling triggers the transcription response of a microRNA, miR-21, in osteoblasts, which is transferred to osteoclast progenitors via exosomes for dictating osteoclastogenesis. After confirming that miR-21 deficiency retards the β1/2-AR agonist isoproterenol (ISO)-induced osteopenia, it is shown that the pharmacological inhibition of exosome release by two clinically-relevant drugs, dimethyl amiloride and omeprazole, suppresses osteoblastic miR-21 transfer and ameliorates bone loss under both ISO and chronic variable stress (CVS)-induced depression conditions. A targeted delivery approach to specifically silence osteoblastic miR-21 is further applied, which is effective in rescuing the bone remodeling balance and ameliorating ISO- and CVS-induced osteopenias. These results decipher a previously unrecognized paradigm that neural cues drive exosomal microRNA communication to regulate organ homeostasis and help to establish feasible strategies to counteract bone loss under psychological stresses.

Receptor-Mediated Targeted Delivery of Surface-ModifiedNanomedicine in Breast Cancer: Recent Update and Challenges.

Breast cancer therapeutic intervention continues to be ambiguous owing to the lack of strategies for targeted transport and receptor-mediated uptake of drugs by cancer cells. In addition to this, sporadic tumor microenvironment, prominent restrictions with conventional chemotherapy, and multidrug-resistant mechanisms of breast cancer cells possess a big challenge to even otherwise optimal and efficacious breast cancer treatment strategies. Surface-modified nanomedicines can expedite the cellular uptake and delivery of drug-loaded nanoparticulate constructs through binding with specific receptors overexpressed aberrantly on the tumor cell. The present review elucidates the interesting yet challenging concept of targeted delivery approaches by exploiting different types of nanoparticulate systems with multiple targeting ligands to target overexpressed receptors of breast cancer cells. The therapeutic efficacy of these novel approaches in preclinical models is also comprehensively discussed in this review. It is concluded from critical analysis of related literature that insight into the translational gap between laboratories and clinical settings would provide the possible future directions to plug the loopholes in the process of development of these receptor-targeted nanomedicines for the treatment of breast cancer.