Options of Therapeutics and Novel Delivery Systems of Drugs for the Treatment of Melanoma.

Melanoma is one of the most severe cancerous diseases. The cells employ multiple signaling pathways, such as ERK, HGF/c-MET, WNT, and COX-2 to cause the cell proliferation, survival, and metastasis. Treatment of melanoma, including surgery, chemotherapy, immunotherapy, radiation, and targeted therapy, is based on 4 major or 11 substages of the disease. Fourteen drugs, including dacarbazine, interferon α-2b, interleukin-12, ipilimumab, peginterferon α-2b, vemurafenib, trametinib, talimogene laherparepvec, cobimetinib, pembrolizumab, dabrafenib, binimetinib, encorafenib, and nivolumab, have been approved by the FDA for the treatment of melanoma. All of them are in conventional dosage forms of injection solutions, suspensions, oral tablets, or capsules. Major drawbacks of the treatment are side effects of the drugs and patients' incompliance to them. These are consequences of high doses and long-term treatments for the diseases. Currently more than 350 NCI-registered clinical trials are being carried out to treat advanced and/or metastatic melanoma using novel treatment methods, such as immune cell therapy, cancer vaccines, and new therapeutic targets. In addition, novel delivery systems using biomaterials of the approved drugs have been developed attempting to increase the drug delivery, targeting, stability, bioavailability, thus potentially reducing the toxicity and increasing the treatment effectiveness. Nanoparticles and liposomes have been emerging as advanced delivery systems which can improve drug stability and systemic circulation time. In this review, the most recent findings in the options for treatment and development of novel drug delivery systems for the treatment of melanoma are comprehensively discussed.

A Detailed Review on Synthesis, Functionalization, Application, Challenges, and Current Status of Magnetic Nanoparticles in the Field of Drug Delivery and Gene Delivery System.

For progression of health care system, it has always been a challenge to the researchers for formulation to a type of advanced drug delivery system which will have less toxicity, targeted delivery and will be highly biodegradable. Nano science or nanotechnology has been validated to be a successful method as of targeting the drug to its active site be due to its special physicochemical properties and size thereby reducing the dose of administration, increasing bioavailability, and also reducing toxicity. Magnetic nanoparticles recently in few decades have proved as an effective advanced drug delivery system for its elevated magnetic responsiveness, biocompatibility, elevated targeted drug delivery effectiveness, etc. The drug can be easily targeted to active site by application of external magnetic field. Among the various elements, nanoparticles prepared with magnetically active iron oxide or other iron-based spinel oxide nanoparticles are widely used due to its high electrical resistivity, mechanical hardness, chemical stability, etc. Owing to their easy execution towards drug delivery application, extensive research has been carried out in this area. This review paper has summarized all recent modifications of iron-based magnetically active nanoparticle based drug delivery system along with their synthesis, characterization, and applications.

Formulation development and process analysis of drug-loaded filaments manufactured via hot-melt extrusion for 3D-printing of medicines.

Three dimensional(3D)-printing via fused deposition modeling (FDM) allows the production of individualized solid dosage forms. However, for bringing this benefit to the patient, active pharmaceutical ingredient (API)-loaded filaments of pharmaceutical grade excipients are necessary as feedstock and have to be produced industrially. As large-scale production of API-loaded filaments has not been described in literature, this study presents a development of 3D-printable filaments, which can continuously be produced via hot-melt extrusion. Further, a combination of testing methods for mechanical resilience of filaments was applied to improve the prediction of their printability. Eudragit RL was chosen as a sustained release polymer and theophylline (30%) as thermally stable model drug. Stearic acid (7%) and polyethylene glycol 4000 (10%), were evaluated as suitable plasticizers for producing 3D-printable filaments. The two formulations were printed into solid dosage forms and analyzed regarding their dissolution profiles. This revealed that stearic acid maintained sustained release properties of the matrix whereas polyethylene glycol 4000 did not. Analysis of the continuous extrusion process was done using a design of experiments. It showed that powder feed rate and speed of the stretching device used after extrusion predominantly determine the diameter of the filament and thereby the mechanical resilience of a filament.

3D-Printed Network Structures as Controlled-Release Drug Delivery Systems: Dose Adjustment, API Release Analysis and Prediction.

3D printing evolved as a promising technique to improve individualization of drug therapy. In particular, when printing sustained release solid dosage forms, as for instance implants, inserts, and also tablets, estimation of the drug release profile in vivo is necessary. In most cases, corresponding analyses cannot be performed at hospital or community pharmacies. Therefore, the present study aimed to develop a sustained release drug delivery system produced via 3D printing, which allows dose adaption and estimation of drug release at the same time. Filaments as feedstock for the printer were produced via hot-melt extrusion and consisted of Eudragit® RL as sustained release polymer, 30% theophylline as model active pharmaceutical ingredient, and stearic acid as solid plasticizer. Assuming that the surface/mass ratio was constant, network structures of different densities were printed as novel solid dosage form. Their weight (263 to 668 mg), thereby their dose, and surface area, determined using X-ray microcomputed tomography, showed a linear correlation with the fill density. The specific surface area of the network hardly varied with changing fill density. Dissolution studies showed a slower drug release for dosage forms with a denser network. Higuchi's model was used for prediction of drug release and showed limited applicability due to different release kinetics for different fill densities. However, using linear interpolation for the prediction resulted in good RMSEP values between 1.4 and 3.7%. These findings might be useful to enable customized production of sustained release solid dosage forms via 3D printing in hospital and community pharmacies in the future.

The modulation of physicochemical characterization of innovative liposomal platforms: the role of the grafted thermoresponsive polymers.

This study is focused on chimeric advanced drug delivery systems and specifically on thermosensitive liposomes, combining lipids and thermoresponsive polymers. In this investigation, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) chimeric liposomal systems were prepared, incorporating the homopolymer C12H25-poly(N-isopropylacrylamide)-COOH (C12H25-PNIPAM-COOH) and the block copolymer poly(n-butylacrylate-b-N-isoropylacrylamide) (PnBA-PNIPAM), at six different molar ratios. Both of these polymers contain the thermoresponsive PNIPAM block, which exhibits lower critical solution temperature (LCST) at 32 °C in aqueous solutions, changing its nature from hydrophilic to hydrophobic above LCST. During the preparation of liposomes, the dispersions were observed visually, while after the preparation we studied the alterations of the physicochemical characteristics, by measuring the size, size distribution and ζ-potential of prepared liposomes. The presence of polymer, either C12H25-PNIPAM-COOH or PnBA-PNIPAM, resulted in liposomes exhibiting different physicochemical characteristics in comparison to conventional DPPC liposomes. At the highest percentage of the polymeric guest, chimeric liposomes were found to retain their size during the stability studies. The incorporation of the appropriate amount of these novel thermoresponsive polymers yields liposomal stabilization and imparts thermoresponsiveness, due to the functional PNIPAM block.

Cellular probing using phytoceuticals encapsulated advanced delivery systems in ameliorating lung diseases: Current trends and future prospects.

Chronic respiratory diseases such as Chronic Obstructive Pulmonary Disease (COPD) and asthma have posed a significant healthcare and economic cost over a prolonged duration worldwide. At present, available treatments are limited to a range of preventive medicines, such as mono- or multiple-drug therapy, which necessitates daily use and are not considered as viable treatments to reverse the inflammatory processes of airway remodelling which is inclusive of the alteration of intra and extracellular matrix of the airway tract, death of epithelial cells, the increase in smooth muscle cell and the activation of fibroblasts. Hence, with the problem in mind a considerable body of study has been dedicated to comprehending the underlying factors that contribute to inflammation within the framework of these disorders. Hence, adequate literature that has unveiled the necessary cellular probing to reduce inflammation in the respiratory tract by improving the selectivity and precision of a novel treatment. However, through cellular probing cellular mechanisms such as the downregulation of various markers, interleukin 8, (IL-8), Interleukin 6 (IL-6), interleukin 1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) have been uncovered. Hence, to target such cellular probes implementation of phytoceuticals encapsulated in an advanced drug delivery system has shown potential to be a solution with in vitro and in vivo studies highlighting their anti-inflammatory and antioxidant effects. However, the high costs associated with advanced drug delivery systems and the limited literature focused exclusively on nanoparticles pose significant challenges. Additionally, the biochemical characteristics of phytoceuticals due to poor solubility, limited bioavailability, and difficulties in mass production makes it difficult to implement this product as a treatment for COPD and asthma. This study aims to examine the integration of many critical features in the context of their application for the treatment of chronic inflammation in respiratory disorders.

Fisetin from Dietary Supplement to a Drug Candidate: An Assessment of Potential

Fisetin is a bioactive compound found in numerous fruits and vegetables, including strawberries, apples, grapes, persimmon, cucumber, onion, etc. The compound is also wellknown for its neurotrophic, anti-inflammatory, anti-carcinogenic, anti-diabetic, and other healthpromoting properties. Although there is increasing agreement that it has therapeutic properties, but its poor water solubility, high lipophilicity, and lower oral bioavailability make it difficult to use clinically. Extensive research has attempted to overcome these restrictions by developing novel and superior delivery systems. Considering the diverse potential, this review is the first to summarise the available data on Fisetin to collate the information related to analytical methods, pharmacological action, their mechanisms, regulatory aspects, and toxicity profile. It also covers the marketed products, related clinical trials, and patent updates of the moiety. In addition, an endeavor has been attempted to discuss and assess the various drug delivery systems employed to increase the biological attributes of Fisetin. The presented manuscript is the first to present a compendium of up-to-date literature on all of the domains considered necessary for this type of natural molecule to carve down its path from being a mere dietary supplement to a promising therapeutic drug candidate. The manuscript is expected to benefit the researchers working on natural and bioactive compounds, industrial scientists, and the general population interested in Fesitin.

18-ß-glycyrrhetinic acid-loaded polymeric nanoparticles attenuate cigarette smoke-induced markers of impaired antiviral response in vitro.

Tobacco smoking is a leading cause of preventable mortality, and it is the major contributor to diseases such as COPD and lung cancer. Cigarette smoke compromises the pulmonary antiviral immune response, increasing susceptibility to viral infections. There is currently no therapy that specifically addresses the problem of impaired antiviral response in cigarette smokers and COPD patients, highlighting the necessity to develop novel treatment strategies. 18-ß-glycyrrhetinic acid (18-ß-gly) is a phytoceutical derived from licorice with promising anti-inflammatory, antioxidant, and antiviral activities whose clinical application is hampered by poor solubility. This study explores the therapeutic potential of an advanced drug delivery system encapsulating 18-ß-gly in poly lactic-co-glycolic acid (PLGA) nanoparticles in addressing the impaired antiviral immunity observed in smokers and COPD patients. Exposure of BCi-NS1.1 human bronchial epithelial cells to cigarette smoke extract (CSE) resulted in reduced expression of critical antiviral chemokines (IP-10, I-TAC, MIP-1α/1ß), mimicking what happens in smokers and COPD patients. Treatment with 18-ß-gly-PLGA nanoparticles partially restored the expression of these chemokines, demonstrating promising therapeutic impact. The nanoparticles increased IP-10, I-TAC, and MIP-1α/1ß levels, exhibiting potential in attenuating the negative effects of cigarette smoke on the antiviral response. This study provides a novel approach to address the impaired antiviral immune response in vulnerable populations, offering a foundation for further investigations and potential therapeutic interventions. Further studies, including a comprehensive in vitro characterization and in vivo testing, are warranted to validate the therapeutic efficacy of 18-ß-gly-PLGA nanoparticles in respiratory disorders associated with compromised antiviral immunity.

Chitosan and hyaluronic acid-based nanocarriers for advanced cancer therapy and intervention.

Cancer has become a major public health issue leading to one of the foremost causes of morbidity and death in the world. Despite the current advances in diagnosis using modern technologies and treatment via surgery or chemo- and radio-therapies, severe side effects or after-effects limit the application of these treatment modalities. Novel drug delivery systems have shown the potential to deliver chemotherapeutics directly to cancer cells, thus minimizing unnecessary exposure to healthy cells. Concurrently, to circumvent difficulties associated with conventional deliveries of cancer therapeutics, natural polysaccharides have gained attention for the fabrication of such deliveries owing to biocompatibility, low toxicity, and biodegradability. It has been exhibited that natural polysaccharides can deliver high therapeutic concentrations of the entrapped drug to the target cells by sustained and targeted release. Considering the immense potential of natural polymers, the present work focuses on naturally generated biopolymer carriers based on chitosan and hyaluronic acid. This review delineated on the role of chitosan and its derivation from renewable resources as a biocompatible, biodegradable, nonimmunogenic material with notable antitumor activity as a drug delivery carrier in oncotherapy. Moreover, hyaluronic acid, itself by its structure or when linked with other molecules contributes to developing promising pharmaceutical delivery systems to setback the restrictions related to conventional cancer treatment.

Alzheimer's disease current therapies, novel drug delivery systems and future directions for better disease management.

Alzheimer's disease (AD), is a neurodegenerative disorder that escalates with time, exerting a significant impact on physical and mental health and leading to death. The prevalence of AD is progressively rising along with its associated economic burden and necessitates effective therapeutic approaches in the near future. This review paper aims to offer an insightful overview of disease pathogenesis, current FDA-approved drugs, and drugs in different clinical phases. It also explores innovative formulations and drug delivery strategies, focusing on nanocarriers and long-acting medications (LAMs) to enhance treatment efficacy and patient adherence. The review also emphasizes preclinical evidence related to nanocarriers and their potential to improve drug bioavailability, pharmacokinetics, and pharmacodynamics parameters, while also highlighting their ability to minimize systemic side effects. By providing a comprehensive analysis, this review furnishes valuable insights into different pathophysiological mechanisms for future drug development. It aims to inform the development of treatment strategies and innovative formulation approaches for delivering existing molecules in Alzheimer's disease, ultimately striving to improve patient compliance.

Challenges and opportunities in delivering oral peptides and proteins.

INTRODUCTION: Rapid advances in bioengineering enable the use of complex proteins as therapeutic agents to treat diseases. Compared with conventional small molecule drugs, proteins have multiple advantages, including high bioactivity and specificity with low toxicity. Developing oral dosage forms with active proteins is a route to improve patient compliance and significantly reduce production costs. However, the gastrointestinal environment remains a challenge to this delivery path due to enzymatic degradation, low permeability, and weak absorption, leading to reduced delivery efficiency and poor clinical outcomes. AREAS COVERED: This review describes the barriers to oral delivery of peptides and complex proteins, current oral delivery strategies utilized and the opportunities and challenges ahead to try and circumvent these barriers. Oral protein drugs on the market and clinical trials provide insights and approaches for advancing delivery strategies. EXPERT OPINION: Although most current studies on oral protein delivery rely on in vitro and in vivo animal data, the safety and limitations of the approach in humans remain uncertain. The shortage of clinical data limits the development of new or alternative strategies. Therefore, designing appropriate oral delivery strategies remains a significant challenge and requires new ideas, innovative design strategies and novel model systems.

Advanced Drug Delivery System for Management of Chronic Diabetes Wound Healing.

The diabetic wound is excessively vulnerable to infection because the diabetic wound suggests delayed and incomplete healing techniques. Presently, wounds and ulcers related to diabetes have additionally increased the medical burden. A diabetic wound can impair mobility, lead to amputations, or even death. In recent times, advanced drug delivery systems have emerged as promising approaches for enhancing the efficacy of wound healing treatments in diabetic patients. This review aims to provide an overview of the current advancements in drug delivery systems in managing chronic diabetic wound healing. This review begins by discussing the pathophysiological features of diabetic wounds, including impaired angiogenesis, elevated reactive oxygen species, and compromised immune response. These factors contribute to delayed wound healing and increased susceptibility to infection. The importance of early intervention and effective wound management strategies is emphasized. Various types of advanced drug delivery systems are then explored, including nanoparticles, hydrogels, transferosomes, liposomes, niosomes, dendrimers, and nanosuspension with incorporated bioactive agents and biological macromolecules are also utilized for chronic diabetes wound management. These systems offer advantages such as sustained release of therapeutic agents, improved targeting and penetration, and enhanced wound closure. Additionally, the review highlights the potential of novel approaches such as antibiotics, minerals, vitamins, growth factors gene therapy, and stem cell-based therapy in diabetic wound healing. The outcome of advanced drug delivery systems holds immense potential in managing chronic diabetic wound healing. They offer innovative approaches for delivering therapeutic agents, improving wound closure, and addressing the specific pathophysiological characteristics of diabetic wounds.

Cationic starch: A functionalized polysaccharide based polymer for advancement of drug delivery and health care system - A review.

Research and development in health care industry is in persistence progression. To make it more patient-friendly or to get maximum benefits from it, special attention to different advanced drug delivery system (ADDS) is employed that delivers the drug at the target site and will be able to sustain/control release of drugs. ADDS should be non-toxic, biodegradable, biocompatible along with desirable showing physicochemical and functional properties. These drug delivery systems can be totally based on polymers, either with natural or synthetic polymers. The molecular weight of polymer can be tuned and different groups of polymers can be modified or substituted with other functional groups. Degree of substitution is also tailored. Cationic starch in recent years is exploited in drug delivery, tissue engineering and biomedicine. Due to their abundant availability, low cost, easy chemical modification, low toxicity, biodegradability and biocompatibility, extensive research is now being carried out. Our present discussion will shed light on the usage of cationic starch in health care system.

Advanced Drug Delivery Modulation via Hybrid Nanofibers Enhances Stem Cell Differentiation.

Seamlessly integrating soluble factors onto biomedical scaffolds with a precisely manufactured topography for efficient cell control remains elusive since many scaffold fabrication techniques degrade payloads. Surface adsorption of payloads onto synthesized nanoscaffolds retains bioactivity by removing exposure to harsh processing conditions at the expense of inefficient drug loading and uncontrolled release. Herein, we present a nanomaterial composite scaffold paradigm to improve physicochemical surface adsorption pharmacokinetics. As a proof of concept, we integrated graphene oxide (GO) and manganese dioxide (MnO2) nanosheets onto nanofibers to increase loading capacity and tune drug release. Non-degradable GO enhances payload retention, while biodegradable MnO2 enables cell-responsive drug release. To demonstrate the utility of this hybrid nanomaterial scaffold paradigm for tissue engineering, we adsorbed payloads ranging from small molecules to proteins onto the scaffold to induce myogenesis and osteogenesis for multiple stem cell lines. Scaffolds with adsorbed payloads enabled more efficient differentiation than media supplementation using equivalent quantities of differentiation factors. We attribute this increased efficacy to a reverse uptake mechanism whereby payloads are localized around seeded cells, increasing delivery efficiency for guiding differentiation. Additionally, we demonstrate spatial control over cells since differentiation factors are delivered locally through the scaffold. When co-culturing scaffolds with and without adsorbed payloads, only cells seeded on payload-adsorbed scaffolds underwent differentiation. With this modular technology being capable of enhancing multiple differentiation fates for specific cell lines, this technology provides a promising alternative for current tissue engineering scaffolds.

Advancements in the Design and Development of Dry Powder Inhalers and Potential Implications for Generic Development.

Dry powder inhalers (DPIs) are drug-device combination products where the complexity of the formulation, its interaction with the device, and input from users play important roles in the drug delivery. As the landscape of DPI products advances with new powder formulations and novel device designs, understanding how these advancements impact performance can aid in developing generics that are therapeutically equivalent to the reference listed drug (RLD) products. This review details the current understanding of the formulation and device related principles driving DPI performance, past and present research efforts to characterize these performance factors, and the implications that advances in formulation and device design may present for evaluating bioequivalence (BE) for generic development.

Phytantriol-Based Berberine-Loaded Liquid Crystalline Nanoparticles Attenuate Inflammation and Oxidative Stress in Lipopolysaccharide-Induced RAW264.7 Macrophages.

Inflammation and oxidative stress are interrelated processes that represent the underlying causes of several chronic inflammatory diseases that include asthma, cystic fibrosis, chronic obstructive pulmonary disease (COPD), allergies, diabetes, and cardiovascular diseases. Macrophages are key initiators of inflammatory processes in the body. When triggered by a stimulus such as bacterial lipopolysaccharides (LPS), these cells secrete inflammatory cytokines namely TNF-α that orchestrate the cellular inflammatory process. Simultaneously, pro-inflammatory stimuli induce the upregulation of inducible nitric oxide synthase (iNOS) which catalyzes the generation of high levels of nitric oxide (NO). This, together with high concentrations of reactive oxygen species (ROS) produced by macrophages, mediate oxidative stress which, in turn, exacerbates inflammation in a feedback loop, resulting in the pathogenesis of several chronic inflammatory diseases. Berberine is a phytochemical embedded with potent in vitro anti-inflammatory and antioxidant properties, whose therapeutic application is hindered by poor solubility and bioavailability. For this reason, large doses of berberine need to be administered to achieve the desired pharmacological effect, which may result in toxicity. Encapsulation of such a drug in liquid crystalline nanoparticles (LCNs) represents a viable strategy to overcome these limitations. We encapsulated berberine in phytantriol-based LCNs (BP-LCNs) and tested the antioxidant and anti-inflammatory activities of BP-LCNs in vitro on LPS-induced mouse RAW264.7 macrophages. BP-LCNs showed potent anti-inflammatory and antioxidant activities, with significant reduction in the gene expressions of TNF-α and iNOS, followed by concomitant reduction of ROS and NO production at a concentration of 2.5 µM, which is lower than the concentration of free berberine concentration required to achieve similar effects as reported elsewhere. Furthermore, we provide evidence for the suitability for BP-LCNs both as an antioxidant and as an anti-inflammatory agent with potential application in the therapy of chronic inflammatory diseases.

Exploring the role of mesoporous silica nanoparticle in the development of novel drug delivery systems.

The biocompatible nature of mesoporous silica nanoparticles (MSN) attracted researchers' attention to deliver therapeutic agents in the treatment of various diseases, where their porous nature, high drug loading efficiency, and suitability to functionalize with a specific ligand of MSN helped to obtain the desired outcome. The application of MSN has been extended to deliver small chemicals to large-sized peptides or proteins to fight against complex diseases. Recently, formulation researches with MSN have been progressed for various non-conventional drug delivery systems, including liposome, microsphere, oro-dispersible film, 3D-printed formulation, and microneedle. Low bulk density, retaining mesoporous structure during downstream processing, and lack of sufficient in vivo studies are some of the important issues towards the success of mesoporous silica-based advanced drug delivery systems. The present review has aimed to evaluate the application of MSN in advanced drug delivery systems to critically analyze the role of MSN in the respective formulation over other functionalized polymers. Finally, an outlook on the future direction of MSN-based advanced drug delivery systems has been drawn against the existing challenges with this platform.

Nanotherapeutics and Nanotheragnostics for Cancers: Properties, Pharmacokinetics, Biopharmaceutics, and Biosafety.

With the increasing worldwide rate of chronic diseases, such as cancer, the development of novel techniques to improve the efficacy of therapeutic agents is highly demanded. Nanoparticles are especially well suited to encapsulate drugs and other therapeutic agents, bringing additional advantages, such as less frequent dosage requirements, reduced side effects due to specific targeting, and therefore increased patient compliance. However, with the increasing use of nanoparticles and their recent launch on the pharmaceutical market, it is important to achieve high-quality control of these advanced systems. In this review, we discuss the properties of different nanoparticles, the pharmacokinetics, the biosafety issues of concern, and conclude with novel nanotherapeutics and nanotheragnostics for cancer drug delivery.

To infinity and beyond: Strategies for fabricating medicines in outer space.

Recent advancements in next generation spacecrafts have reignited public excitement over life beyond Earth. However, to safeguard the health and safety of humans in the hostile environment of space, innovation in pharmaceutical manufacturing and drug delivery deserves urgent attention. In this review/commentary, the current state of medicines provision in space is explored, accompanied by a forward look on the future of pharmaceutical manufacturing in outer space. The hazards associated with spaceflight, and their corresponding medical problems, are first briefly discussed. Subsequently, the infeasibility of present-day medicines provision systems for supporting deep space exploration is examined. The existing knowledge gaps on the altered clinical effects of medicines in space are evaluated, and suggestions are provided on how clinical trials in space might be conducted. An envisioned model of on-site production and delivery of medicines in space is proposed, referencing emerging technologies (e.g. Chemputing, synthetic biology, and 3D printing) being developed on Earth that may be adapted for extra-terrestrial use. This review concludes with a critical analysis on the regulatory considerations necessary to facilitate the adoption of these technologies and proposes a framework by which these may be enforced. In doing so, this commentary aims to instigate discussions on the pharmaceutical needs of deep space exploration, and strategies on how these may be met.

Enhanced siRNA Delivery and Selective Apoptosis Induction in H1299 Cancer Cells by Layer-by-Layer-Assembled Se Nanocomplexes: Toward More Efficient Cancer Therapy.

Nanotechnology has made an important contribution to oncology in recent years, especially for drug delivery. While many different nano-delivery systems have been suggested for cancer therapy, selenium nanoparticles (SeNPs) are particularly promising anticancer drug carriers as their core material offers interesting synergistic effects to cancer cells. Se compounds can exert cytotoxic effects by acting as pro-oxidants that alter cellular redox homeostasis, eventually leading to apoptosis induction in many kinds of cancer cells. Herein, we report on the design and synthesis of novel layer-by-layer Se-based nanocomplexes (LBL-Se-NCs) as carriers of small interfering RNA (siRNA) for combined gene silencing and apoptosis induction in cancer cells. The LBL-Se-NCs were prepared using a straightforward electrostatic assembly of siRNA and chitosan (CS) on the solid core of the SeNP. In this study, we started by investigating the colloidal stability and protection of the complexed siRNA. The results show that CS not only functioned as an anchoring layer for siRNA, but also provided colloidal stability for at least 20 days in different media when CS was applied as a third layer. The release study revealed that siRNA remained better associated with LBL-Se-NCs, with only a release of 35% after 7 days, as compared to CS-NCs with a siRNA release of 100% after 48 h, making the LBL nanocarrier an excellent candidate as an off-the-shelf formulation. When applied to H1299 cells, it was found that they can selectively induce around 32% apoptosis, while significantly less apoptosis (5.6%) was induced in NIH/3T3 normal cells. At the same time, they were capable of efficiently inducing siRNA downregulation (35%) without loss of activity 7 days post-synthesis. We conclude that LBL-Se-NCs are promising siRNA carriers with enhanced stability and with a dual mode of action against cancer cells.