Design and Evaluation of Inorganic/Organic Hybrid Bio-composite for Site-Specific Oral Delivery of Darifenacin.

Benign hyperplasia (BHP) is a common disorder that affects men over the age of 60 years. Transurethral resection of the prostate (TURP) is the gold standard for operative treatment, but a range of drugs are also available to improve quality of life and to reduce BHP-associated urinary tract infections and complications. Darifenacin, an anti-muscarinic agent, has been found effective for relieving symptoms of overactive bladder associated with BHP, but the drug has poor solubility and bioavailability, which are major challenges in product development. An inorganic/organic bio-composite with gastric pH-resistant property was synthesized for the targeted oral delivery of Darifenacin to the lower gastrointestinal tract (GIT). This development was accomplished through co-precipitation of calcium carbonate in quince seed-based mucilage. The FTIR, XRD, DSC, and TGA results showed good drug-polymer compatibility, and the SEM images showed calcite formation in the quince hydrogel system. After 72 h, the drug release of 34% and 75% were observed in acidic (0.1N HCl) and 6.8 pH phosphate buffer, respectively. A restricted/less drug was permeated through gastric membrane (21.8%) as compared to permeation through intestinal membrane (65%.) The developed composite showed significant reduction in testosterone-induced prostatic hyperplasia (2.39 ± 0.12***) as compared to untreated diseased animal group. No sign of organ toxicity was observed against all the developed composites. In this study, we developed an inorganic-organic composite system that is highly biocompatible and effective for targeting the lower GIT, thereby avoiding the first-pass metabolism of darifenacin.

An overview of phospholipid enriched-edge activator-based vesicle nanocarriers: New paradigms to treat skin cancer.

Skin cancer poses a significant global health concern necessitating innovative treatment approaches. This review explores the potential of vesicle nanoformulation incorporating EA (edge activators) to overcome barriers in skin cancer management. The skin's inherent protective mechanisms, specifically the outermost layer called the stratum corneum and the network of blood arteries, impede the permeation of drugs. Phospholipid-enriched EA based nanoformulation offer a promising solution by enhancing drug penetration through skin barriers. EAs like Span 80, Span 20, Tween 20, and sodium cholate etc., enhance vesicles deformability, influencing drug permeation. This review discusses topical application of drugs treat skin cancer, highlighting challenges connected with the conventional liposome and the significance of using EA-based nanoformulation in overcoming these challenges. Furthermore, it provides insights into various EA characteristics, critical insights, clinical trials, and patents. The review also offers a concise overview of composition, preparation techniques, and the application of EA-based nanoformulation such as transfersomes, transliposomes, transethosomes, and transniosomes for delivering drugs to treat skin cancer. Overall, this review intends to accelerate the development of formulations that incorporate EA, which would further improve topical drug delivery and enhance therapeutic outcomes in skin cancer treatment.

Microgel delivery systems of functional substances for precision nutrition.

Microgels delivery system have great potential in functional substances encapsulation, protection, release, precise delivery and nutritional intervention. Microgel is a three-dimensional network structure formed by physical or chemical crosslinking of biopolymers, whose characteristics include dispersion and swelling, stable structure, small volume and high specific surface area, and is a special kind of colloid. In this chapter, the common wall materials for preparing food grade microgels, and the main preparation principles, methods, advantages and disadvantages of microgels loaded with functional substances were firstly reviewed. Then the main characteristics of microgel as delivery system, such as deformability, high encapsulation, stimulus-responsive release and targeted delivery, and its potential benefits in intervening chronic diseases were summarized. Finally, the applications of microgel delivery system for functional substance in the field of precision nutrition were discussed. This chapter will help to design of next-generation advanced targeting microgel delivery system, and realize precision nutrition intervention of food functional substances on body health.

Dihydroxyphenylalanine-conjugated high molecular weight polyethylenimine for targeted delivery of Plasmid.

High molecular weight polyethylenimine (HMW PEI; branched 25 kDa PEI) has been widely investigated for gene delivery due to its high transfection efficiency. However, the toxicity and lack of targeting to specific cells have limited its clinical application. In the present investigation, L-3, 4-dihydroxyphenylalanine (L-DOPA) was conjugated on HMW PEI in order to target L-type amino acid transporter 1 (LAT-1) and modulate positive charge density on the surface of polymer/plasmid complexes (polyplexes). The results of biophysical characterization revealed that the PEI conjugates are able to form nanoparticles ≤ 180 nm with the zeta potential ranging from + 9.5-12.4 mV. These polyplexes could condense plasmid DNA and protect it against nuclease digestion at the carrier to plasmid ratios higher than 4. L-DOPA conjugated PEI derivatives were complexed with a plasmid encoding human interleukin-12 (hIL-12). Targeted polyplexes showed up to 2.5 fold higher transfection efficiency in 4T1 murine mammary cancer cell line, which expresses LAT-1, than 25 kDa PEI polyplexes prepared in the same manner. The cytotoxicity of these polyplexes was also substantially lower than the unmodified parent HMW PEI. These results support the use of L-3, 4-dihydroxyphenylalanine derivatives of PEI in any attempt to develop a LAT-1 targeted gene carrier.

Microencapsule delivery systems of functional substances for precision nutrition.

Microencapsulation, a typical core-shell structure technology, encapsulates functional active ingredients for protection, controlled release, and targeted delivery. In precise nutrition, the focus is on utilizing microcapsule delivery systems for personalized dietary supplements and disease intervention. This chapter outlines the morphological structure of microcapsules, common wall materials, and preparation techniques. It discusses the characteristics of different hydrophilic and lipophilic functional factors and their function as dietary supplements. The role of microencapsulation on the controlled release, odor masking, and enhanced bioavailability of functional factors is explored. Additionally, the application of microcapsule delivery systems in nutritional interventions for diseases like inflammatory bowel disease, alcoholic/fatty liver disease, diabetes, and cancer is introduced in detail. Lastly, the chapter proposes the future developments of anticipation in responsive wall materials for precise nutrition interventions, including both challenges and opportunities.

Membrane-coated nanoparticles as a biomimetic targeted delivery system for tumour therapy.

Drug therapy towards tumours often causes adverse effects because of their non-specific nature. Membrane-coated technology and membrane-coated nanoparticles provide an advanced and promising platform of targeted and safe delivery. By camouflaging the nanoparticles with natural derived or artificially modified cell membranes, the nano-payloads are bestowed with properties from cell membranes such as longer circulation, tumour or inflammation-targeting, immune stimulation, augmenting the performance of traditional therapeutics. In this review, we review the development of membrane coating technology, and summarise the technical details, physicochemical properties, and research status of membrane-coated nanoparticles from different sources in tumour treatment. Finally, we also look forward to the prospects and challenges of transforming membrane coating technology from experiment into clinical use. Taken together, membrane-coated nanoparticles are bound to become one of the most potential anti-tumour strategies in the future.

Advancements in increasing efficiency of Hydrogen Sulfide in therapeutics: Strategies for targeted delivery as prodrugs.

Hydrogen sulfide (H2S) has emerged as a potent therapeutic agent with diverse physiological functions, including vasodilation, anti-inflammation, and cytoprotection. However, its clinical application is limited due to its volatility and potential toxicity at high concentrations. To address these challenges, researchers have developed various H2S prodrugs that release H2S in a controlled and targeted manner. The review underscores the importance of targeting and delivery strategies in maximizing the therapeutic potential of H2S, a gasotransmitter with diverse physiological functions and therapeutic effects. By summarizing recent advancements, the review provides valuable insights for researchers and clinicians interested in harnessing the therapeutic benefits of H2S while minimizing off-target effects and toxicity. The integration of novel targeting and delivery approaches not only enhances the efficacy of H2S-based therapeutics but also expands the scope of potential applications, offering promising avenues for the development of new treatments for a variety of diseases and disorders.

Recent advances in mesoporous silica nanoparticles formulations and drug delivery for wound healing.

Wound healing is a natural process that can be disrupted by disease. Nanotechnology is a promising platform for the development of new therapeutic agents to accelerate acute and chronic wound healing. Drug delivery by means of nanoparticles as well as wound dressings have emerged as suitable options to improving the healing process. The characteristics of mesoporous silica nanoparticles (MSNs) make them efficient carriers of pharmaceutical agents alone or in combination with dressings. In order to maximize the effect of a drug and minimize its adverse consequences, it may be possible to include targeted and intelligent release of the drug into the design of MSNs. Its use to facilitate closure of adjacent sides of a cut as a tissue adhesive, local wound healing, controlled drug release and induction of blood coagulation are possible applications of MSNs. This review summarizes research on MSN applications for wound healing. It includes a general overview, wound healing phases, MSN formulation, therapeutic possibilities of MSNs and MSN-based drug delivery systems for wound healing.

Albumin incorporation into recognising layer of HER2-specific magnetic nanoparticles as a tool for optimal targeting of the acidic tumor microenvironment.

Cancer is unquestionably a global healthcare challenge, spurring the exporation of novel treatment approaches. In recent years, nanomaterials have garnered significant interest with the greatest hopes for targeted nanoformulations due to their cell-specific delivery, improved therapeutic efficacy, and reduced systemic toxicity for the organism. The problem of successful clinical translation of nanoparticles may be related to the fact that most in vitro tests are performed at pH values of normal cells and tissues, ranging from 7.2 to 7.4. The extracellular pH values of tumors are characterized by a shift to a more acidic region in the range of 5.6-7.0 and represent a crucial target for enhancing nanoparticle delivery to cancer cells. Here we show the method of non-active protein incorporation into the surface of HER2-targeted nanoparticles to achieve optimal cellular uptake within the pH range of the tumor microenvironment. The method efficacy was confirmed in vitro and in vivo showing the maximum binding of nanoparticles to cells at a pH value 6.4. Namely, fluorescent magnetic nanoparticles, modified with HER2-recognising affibody ZHER2:342, with proven specificity in terms of HER2 recognition (with 62-fold higher cellular uptake compared to control nanoparticles) were designed for targeting cancer cells at slightly acidic pH values. The stabilizing protein, namely, bovine serum albumin, one of the major blood components with widespread availability and biocompatibility, was used for the decoration of the nanoparticle surface to alter the pH response of the targeting magnetic conjugates. The optimally designed nanoparticles showed a bell-shaped dependency of interaction with cancer cells in the pH range of 5.6-8.0 with maximum cellular uptake at pH value 6.4 close to that of the tumor microenvironment. In vivo experiments revealed that after i.v. administration, BSA-decorated nanoparticles exhibited 2 times higher accumulation in tumors compared to magnetic nanoparticles modified with affibody only. Thus, we demonstrated a valid method for enhancing the specificity of targeted nanoparticle delivery to cancer cells without changing the functional components of nanoparticles.

Surface Engineering of Magnetic Iron Oxide Nanoparticles for Breast Cancer Diagnostics and Drug Delivery.

Data published in 2020 by the International Agency for Research on Cancer (IARC) of the World Health Organization show that breast cancer (BC) has become the most common cancer globally, affecting more than 2 million women each year. The complex tumor microenvironment, drug resistance, metastasis, and poor prognosis constitute the primary challenges in the current diagnosis and treatment of BC. Magnetic iron oxide nanoparticles (MIONPs) have emerged as a promising nanoplatform for diagnostic tumor imaging as well as therapeutic drug-targeted delivery due to their unique physicochemical properties. The extensive surface engineering has given rise to multifunctionalized MIONPs. In this review, the latest advancements in surface modification strategies of MIONPs over the past five years are summarized and categorized as constrast agents and drug delivery platforms. Additionally, the remaining challenges and future prospects of MIONPs-based targeted delivery are discussed.

Engineered lipid nanoparticles enable therapeutic gene silencing of GTSE1 for the treatment of liver fibrosis.

Liver fibrosis is characterized by abnormal accumulation of extracellular matrix proteins, disrupting normal liver function. Despite its significant health impact, effective treatments remain limited. Here, we present the development of engineered lipid nanoparticles (LNPs) for targeted RNA therapeutic delivery in the liver. We investigated the therapeutic potential of modulating the G2 and S-phase expressed 1 (GTSE1) protein for treating liver fibrosis. Through screening, we identified P138Y LNP as a potent candidate with superior delivery efficiency and lower toxicity. Using these engineered LNPs, we successfully delivered siGTSE1 to hepatocytes, significantly reducing collagen accumulation and restoring liver function in a fibrosis animal model. Additionally, GTSE1 downregulation altered miRNA expression and upregulated hepatocyte nuclear factor 4 alpha (HNF4α). These findings suggest that therapeutic gene silencing of GTSE1 is a promising strategy for treating liver fibrosis by regenerating liver phenotypes and functions.

Enhanced targeted liposomal delivery of imiquimod via aptamer functionalization for head and neck cancer therapy.

The incidence of head and neck cancers, particularly those associated with Human Papillomavirus (HPV) infections, has been steadily increasing. Conventional therapies exhibit limitations and drawbacks, prompting the exploration of new strategies over the years, with nanomedicine approaches, especially liposomes gaining relevance. Additionally, the functionalization of liposomes with aptamers enables selective delivery to target cells. For instance, AT11 can serve as a targeting moiety for cancer cells due to its high affinity for nucleolin, a protein overexpressed on the cancer cell's surface. In this study, liposomes functionalized with AT11 are proposed as drug delivery systems for imiquimod (IQ), aiming to maximize its potential as an anticancer agent for HPV-related cancers. To this end, firstly liposomes were produced through the ethanol injection method, functionalized with AT11-TEG-Cholesteryl, and characterized using dynamic light scattering. The obtained liposomes presented suitable properties for cancer therapy (with sizes from 120 to 140 nm and low polydispersity PDI < 0.16) and were further evaluated in terms of potential anticancer effects. AT11 IQ-associated liposomes allowed a selective delivery of IQ towards a tongue cancer cell line (UPCI-SCC-154) relative to the non-malignant cell line (Het1A). Specifically, they induced a selective reduction of the cell viability (∼52 % versus ∼113 %; p < 0.0001), proliferation (∼68 % versus ∼102 %; p<0.0001) and increased cell death (∼7-fold increase; p < 0.0001)). Additionally, they decreased the migration (from ∼24 % to ∼8 %; p < 0.0001) and invasion (to 11 %; p = 0.0047) capacities of the cancer cells. In summary, the produced liposomes represent a promising approach to enhance the anticancer potential of IQ in head and neck cancer, particularly in tongue cancer.

Environment-responsive dopamine nanoplatform for tumor synergistic therapy.

Nanoparticle-based photothermal therapy (PTT) has emerged as a promising approach in tumor treatment due to its high selectivity and low invasiveness. However, the penetration of near-infrared light (NIR) is limited, leading it fails to induce damage to the deep-seated tumor cells within the tumor tissue. Additionally, inefficient uptake of photothermal nanoparticles by tumor cells results in suboptimal outcomes for PTT. In this study, we utilized the adhesive properties of photothermal material, polydopamine (PDA), which can successfully load the photosensitizer indocyanine green (ICG) and chemotherapeutic drug doxorubicin (DOX) to achieve photothermal and chemotherapy synergy treatment (PDA/DOX&ICG), aiming to compensate the defects of single tumor treatment. To extending the blood circulation time of PDA/DOX&ICG nanoparticles, evading clearance by the body immune system and achieving targeted delivery to tumor tissues, a protective envelopment was created using erythrocyte membranes modified with folate acid (FA-EM). After reaching the tumor tissue, the obtained FA-EM@PDA/DOX&ICG nanoparticles can specific bind with folate acid receptors on the surface of tumor cells, which can improve the uptake behavior of FA-EM@PDA/DOX&ICG nanoparticles by tumor cells, and leading to the release of loaded DOX and ICG in response to the unique tumor microenvironment. ICG, as a typical photosensitizer, significantly enhances the photothermal conversion performance of FA-EM@PDA/DOX&ICG nanoparticles, thus inducing tumor cells damage. In vitro and in vivo experimental results demonstrated that the coordinated NIR treatment with FA-EM@PDA/DOX&ICG not only effectively inhibits tumor growth, but also exhibits superior biocompatibility, effectively mitigating DOX-induced tissue damage.

Developments in radionanotheranostic strategies for precision diagnosis and treatment of prostate cancer.

BACKGROUND: Prostate Cancer (PCa) is the second most diagnosed urological cancer among men worldwide. Conventional methods used for diagnosis of PCa have several pitfalls which include lack of sensitivity and specificity. On the other hand, traditional treatment of PCa poses challenges such as long-term side effects and the development of multidrug resistance (MDR). MAIN BODY: Hence, there is a need for novel PCa agents with the potential to lessen the burden of these adverse effects on patients. Nanotechnology has emerged as a promising approach to support both early diagnosis and effective treatment of tumours by ensuring precise delivery of the drug to the targeted site of the disease. Most cancer-related biological processes occur on the nanoscale hence application of nanotechnology has been greatly appreciated and implemented in the management and therapeutics of cancer. Nuclear medicine plays a significant role in the non-invasive diagnosis and treatment of PCa using appropriate radiopharmaceuticals. This review aims to explore the different radiolabelled nanomaterials to enhance the specific delivery of imaging and therapeutic agents to cancer cells. Thereafter, the review appraises the advantages and disadvantages of these modalities and then discusses and outlines the benefits of radiolabelled nanomaterials in targeting cancerous prostatic tumours. Moreover, the nanoradiotheranostic approaches currently developed for PCa are discussed and finally the prospects of combining radiopharmaceuticals with nanotechnology in improving PCa outcomes will be highlighted. CONCLUSION: Nanomaterials have great potential, but safety and biocompatibility issues remain. Notwithstanding, the combination of nanomaterials with radiotherapeutics may improve patient outcomes and quality of life.

Bioderived Nanoparticles for Cardiac Repair.

Biobased therapy represents a promising strategy for myocardial repair. However, the limitations of using live cells, including the risk of immunogenicity of allogeneic cells and inconsistent therapeutic efficacy of autologous cells together with low stability, result in an unsatisfactory clinical outcomes. Therefore, cell-free strategies for cardiac tissue repair have been proposed as alternative strategies. Cell-free strategies, primarily based on the paracrine effects of cellular therapy, have demonstrated their potential to inhibit apoptosis, reduce inflammation, and promote on-site cell migration and proliferation, as well as angiogenesis, after an infarction and have been explored preclinically and clinically. Among various cell-free modalities, bioderived nanoparticles, including adeno-associated virus (AAV), extracellular vesicles, cell membrane-coated nanoparticles, and exosome-mimetic nanovesicles, have emerged as promising strategies due to their improved biological function and therapeutic effect. The main focus of this review is the development of existing cellular nanoparticles and their fundamental working mechanisms, as well as the challenges and opportunities. The key processes and requirements for cardiac tissue repair are summarized first. Various cellular nanoparticle modalities are further highlighted, together with their advantages and limitations. Finally, we discuss various delivery approaches that offer potential pathways for researchers and clinicians to translate cell-free strategies for cardiac tissue repair into clinical practice.

Self-assembled hyaluronic acid nanomicelle for enhanced cascade cancer chemotherapy via self-sensitized ferroptosis.

The clinical utility of chemotherapy is often compromised by its limited efficacy and significant side effects. Addressing these concerns, we have developed a self-assembled nanomicelle, namely SANTA FE OXA, which consists of hyaluronic acid (HA) conjugated with ferrocene methanol (FC), oxaliplatin prodrug (OXA(IV)) and ethylene glycol-coupled linoleic acid (EG-LA). Targeted delivery is achieved by HA binding to the CD44 receptors that are overexpressed on tumor cells, facilitating drug uptake. Once internalized, hyaluronidase (HAase) catalyzes the digestion of the SANTA FE OXA, releasing FC and reducing OXA(IV) into an active form. The active oxaliplatin (OXA) induces DNA damage and increases intracellular hydrogen peroxide (H2O2) levels via cascade reactions. Simultaneously, FC disrupts the redox balance within tumor cells, inducing ferroptosis. Both in vivo and in vitro experiments confirmed that SANTA FE OXA inhibited tumor growth by combining cascade chemotherapy and self-sensitized ferroptosis, achieving a tumor inhibition rate of up to 76.61 %. Moreover, this SANTA FE OXA significantly mitigates the systemic toxicity commonly associated with platinum-based chemotherapeutics. Our findings represent a compelling advancement in nanomedicine for enhanced cascade cancer therapy.

Strategies for Targeting Peptide-Modified Exosomes and Their Applications in the Lungs.

Exosomes belong to a subgroup of extracellular vesicles secreted by various cells and are involved in intercellular communication and material transfer. In recent years, exosomes have been used as drug delivery carriers because of their natural origin, high stability, low immunogenicity and high engineering ability. However, achieving targeted drug delivery with exosomes remains challenging. In this paper, a phage display technology was used to screen targeted peptides, and different surface modification strategies of targeted peptide exosomes were reviewed. In addition, the application of peptide-targeted exosomes in pulmonary diseases was also summarised.

Recent advances in nanoenzymes for Alzheimer's disease treatment.

Alzheimer's disease (AD) remains one of the most challenging neurodegenerative disorders to treat, with oxidative stress playing a significant role in its pathology. Recent advancements in nanoenzymes technology offer a promising approach to mitigate this oxidative damage. Nanoenzymes, with their unique enzyme-mimicking activities, effectively scavenge reactive oxygen species and reduce oxidative stress, thereby providing neuroprotective effects. This review delves into the underlying mechanisms of AD, focusing on oxidative stress and its impact on disease progression. We explore the latest developments in nanoenzymes applications for AD treatment, highlighting their multifunctional capabilities and potential for targeted delivery to amyloid-beta plaques. Despite the exciting prospects, the clinical translation of nanoenzymes faces several challenges, including difficulties in brain targeting, consistent quality production, and ensuring safety and biocompatibility. We discuss these limitations in detail, emphasizing the need for rigorous evaluation and standardized protocols. This paper aims to provide a comprehensive overview of the current state of nanoenzymes research in AD, shedding light on both the opportunities and obstacles in the path towards effective clinical applications.

Magnetically Guided Microcatheter for Targeted Injection of Magnetic Particle Swarms.

The initial delivery of small-scale magnetic devices such as microrobots is a key, but often overlooked, aspect for their use in clinical applications. The deployment of these devices within the dynamic environment of the human body presents significant challenges due to their dispersion caused by circulatory flows. Here, a method is introduced to effectively deliver a swarm of magnetic nanoparticles in fluidic flows. This approach integrates a magnetically navigated robotic microcatheter equipped with a reservoir for storing the magnetic nanoparticles. The microfluidic flow within the reservoir facilitates the injection of magnetic nanoparticles into the fluid stream, and a magnetic field gradient guides the swarm through the oscillatory flow to a target site. The microcatheter and reservoir are engineered to enable magnetic steering and injection of the magnetic nanoparticles. To demonstrate this approach, experiments are conducted utilizing a spinal cord phantom simulating intrathecal catheter delivery for applications in the central nervous system. These results demonstrate that the proposed microcatheter successfully concentrates nanoparticles near the desired location through the precise manipulation of magnetic field gradients, offering a promising solution for the controlled deployment of untethered magnetic micro-/nanodevices within the complex physiological circulatory systems of the human body.

A review of metallic nanoparticles: present issues and prospects focused on the preparation methods, characterization techniques, and their theranostic applications.

Metallic nanoparticles (MNPs) have garnered significant attention due to their ability to improve the therapeutic index of medications by reducing multidrug resistance and effectively delivering therapeutic agents through active targeting. In addition to drug delivery, MNPs have several medical applications, including in vitro and in vivo diagnostics, and they improve the biocompatibility of materials and nutraceuticals. MNPs have several advantages in drug delivery systems and genetic manipulation, such as improved stability and half-life in circulation, passive or active targeting into the desired target selective tissue, and gene manipulation by delivering genetic materials. The main goal of this review is to provide current information on the present issues and prospects of MNPs in drug and gene delivery systems. The current study focused on MNP preparation methods and their characterization by different techniques, their applications to targeted delivery, non-viral vectors in genetic manipulation, and challenges in clinical trial translation.