Nanomedicine Products Research Articles

Development of Stable and Intensified Mixing Processes for the Precise and Scalable Production of Uniform Drug Delivery Nanocarriers.

Nanocarriers show great promise in drug delivery but face challenges in stability, uniformity, and morphology control. This work introduces an enhanced mixing process to overcome these obstacles, specifically aiming to produce consistently sized poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with anti-tumor drugs. By innovatively integrating a pulsation dampener into the microfluidic channels of a continuous flow preparation system, the flow stability of piston pumps is improved nearly tenfold. Consequently, large-scale production of uniformly sized nanoparticles with customizable dimensions is achieved through nanoprecipitation. Furthermore, incorporating terminal double-bond-functionalized poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-maleimide (PLGA-PEG-Mal) enables these nanoparticles to act as nano-crosslinkers. This facilitates in situ crosslinking with thiolated hyaluronic acid via a spontaneous thiol-ene coupling reaction under physiological conditions, allowing for minimally invasive drug administration and significantly enhancing localized drug retention. The material's degradability in the presence of endogenous enzymes ensures controlled drug release, as demonstrated with the anti-tumor drug doxorubicin (DOX). Validation in a murine breast cancer model shows reduced toxicity and a substantial reduction in tumor weight compared to the free DOX group. These findings confirm the approach's effectiveness for breast cancer treatment and pave the way for innovative solutions in nanomedicine, providing a practical microfluidic mixing system for the design and large-scale production of nanomedicines.

Artificial intelligence for computation and development of nanodrug solubility in supercritical solvent: Analysis of temperature and pressure influence

This paper presents an investigation into the modeling and prediction of the density of supercritical carbon dioxide (SC-CO2) and mole fraction of Erlotinib hydrochloride using machine learning techniques. The dataset consists of temperature and pressure as input variables, with density of SC-CO2 and mole fraction of Erlotinib hydrochloride as output variables. The process is supercritical-based operation which can be used for production of nanomedicines with improved aqueous solubility. Three models, Multilayer Perceptron (MLP), Orthogonal Matching Pursuit (OMP), and Extreme Gradient Boosting (XGB) were trained and optimized using the Firefly Optimization Algorithm (FA). The models’ performance in correlating solubility and density were evaluated via statistical analyses to measure their accuracy. The MLP model achieved high accuracy, with scores of 0.99714 and 0.97749 for density and mole fraction prediction, respectively in term of coefficient of determination (R2). The OMP and XGB models also provided reasonably accurate results. These findings demonstrate the effectiveness of machine learning in understanding and predicting SC-CO2 behavior, with potential applications in industrial processes and pharmaceutical formulations.

Nanotherapeutics to cure inflammation-induced cancer

Aims: Nanotherapeutics are being explored as a potential solution to treat inflammation-induced cancer. Nanotherapeutics enhance innate immune cells' immunity, enabling them to fight tumors effectively. These cells secrete specific chemicals like cytokines, allowing them to replicate quickly and respond to future threats, making them suitable for immunotherapy.Methods: Nanotechnology can significantly improve human health by enhancing infection detection, prevention, and treatment. Nanomedicines, composed of restorative and imaging compounds in submicrometer-sized materials, aim to deliver effective treatments and limit inflammation in healthy body areas. Combining nanotechnology and clinical sciences, nanoparticles are suitable for gene therapy and have been developed for treating various diseases, including cancer, cardiovascular, diabetes, pulmonary, and inflammatory diseases.Results: Neutrophils and their offspring, including films and extracellular vehicles, are crucial drug transporters for enhanced growth therapy. Tumor microenvironment inputs can modify tumor-associated neutrophils (TANs), which are essential for tumor growth and healing. Human tumor intratumor heterogeneity is crucial for tumor growth and healing. Nanomedicines have shown potential in targeted delivery, toxicity reduction, and therapeutic effectiveness enhancement. However, clinical relevance and efficacy remain inadequate due to a lack of understanding of the interaction between nanomaterials, nanomedicine, and biology. The diverse biological milieu impacts the dynamic bioidentity of nanoformulations, and their interactions can modify therapeutic function or cellular absorption.Conclusion: Nanotechnology holds great promise for improving human health by detecting, preventing, and treating infections. Nanomedicines, a fusion of clinical sciences and nanotechnology, use submicrometer-sized transporter materials for therapy delivery and reducing contamination. Nanoparticles' small size and high surface-to-volume ratio can benefit gene therapy. Research has led to a wide range of nanomedicine products globally.

Sequential catalytic nanomedicinal utilization for synergistic drug delivery application in cancer nanotechnology

Cancer is the major cause of the increase in the deah rate globally, with an escalating number of cases every year. However, early detection of cancer and its treatment have remained a key challenge. The rapid advancement of nanotechnology toward nanomedicine holds considerable potential for improving cancer therapy techniques. The concept of “nanocatalytic medicine” has emerged due to the rapid proliferation of scientific investigations concerning the biomedical applications of nanocatalysts, which are anticipated to advance the field. This emerging catalytic therapeutic approach is expected to have a bigger impact on the discipline of nanomedicine.The goal of introducing drug delivery systems is to enhance the therapeutic effect or reduce drug toxicity. This manuscript explores an in-depth analysis of the rationale for developing nanomedicine products for cancer therapy. In addition, numerous techniques for the delivery of drugs to tumor cells have been introduced. Following this, catalytic-based nanomedicine employs a diverse array of nanoparticles, which has the potential to be extraordinarily beneficial in the treatment of cancer. This article offers a succinct synopsis of recent advancements in co-delivery agents and nanocarriers, including the characterization of nanocarriers and the successful implementations of drug-delivery cases in synergistic systems.

A Design-Conversed Strategy Establishes the Performance Safe Space for Doxorubicin Nanosimilars.

Nanomedicines exhibit multifaceted performances, yet their biopharmaceutics remain poorly understood and present several challenges in the translation from preclinical to clinical research. To address this issue and promote the production of high-quality nanomedicines, a systematic screening of the design space and in vivo performance is necessary. Establishing formulation performance specifications early on enables an informed selection of candidates and promotes the development of nanosimilars. The deconvolution of the pharmacokinetics enables the identification of key characteristics that influence their performances and disposition. Using an in vitro-in vivo rank-order relationship for doxorubicin nanoformulations, we defined in vitro release specifications for Doxil/Caelyx-like follow-on products. Additionally, our model predictions were used to establish the bioequivalence of Lipodox, a nanosimilar of Doxil/Caelyx. Furthermore, a virtual safe space was established, providing crucial insights into expected disposition kinetics and informing formulation development. By addressing bottlenecks in biopharmaceutics and formulation screening, our research advances the translation of nanomedicine from bench to bedside.

Microfluidic synthesis of lipid-based nanoparticles for drug delivery: recent advances and opportunities.

Microfluidic technologies are revolutionizing the synthesis of nanoscale lipid particles and enabling new opportunities for the production of lipid-based nanomedicines. By harnessing the benefits of microfluidics for controlling diffusive and advective transport within microfabricated flow cells, microfluidic platforms enable unique capabilities for lipid nanoparticle synthesis with precise and tunable control over nanoparticle properties. Here we present an assessment of the current state of microfluidic technologies for lipid-based nanoparticle and nanomedicine production. Microfluidic techniques are discussed in the context of conventional production methods, with an emphasis on the capabilities of microfluidic systems for controlling nanoparticle size and size distribution. Challenges and opportunities associated with the scaling of manufacturing throughput are discussed, together with an overview of emerging microfluidic methods for lipid nanomedicine post-processing. The impact of additive manufacturing on current and future microfluidic platforms is also considered.

Solid Lipid Nanoparticles Enhancing the Leishmanicidal Activity of Delamanid.

Leishmaniasis, a zoonotic parasitic disease transmitted by infected sandflies, impacts nearly 1 million people yearly and is endemic in many countries across Asia, Africa, the Americas, and the Mediterranean; despite this, it remains a neglected disease with limited effective treatments, particularly in impoverished communities with limited access to healthcare. This study aims to repurpose approved drugs for an affordable leishmaniasis treatment. After the screening of potential drug candidates by reviewing databases and utilizing molecular docking analysis, delamanid was chosen to be incorporated into solid lipid nanoparticles (SLNPs). Both in cellulo and in vivo tests confirmed the successful payload release within macrophages and through the epidermis following topical application on murine skin. The evaluation of macrophages infected with L. infantum amastigotes showed that the encapsulated delamanid exhibited greater leishmanicidal activity compared with the free drug. The process of encapsulating delamanid in SLNPs, as demonstrated in this study, places a strong emphasis on employing minimal technology, ensuring energy efficiency, cost-effectiveness, and reproducibility. It enables consistent, low-cost production of nanomedicines, even on a small scale, offering a promising step toward more accessible and effective leishmaniasis treatments.

An Insight into Biochemical Characterization and Explorations of Antioxidant, Antibacterial, Cytotoxic, and Antidiabetic Activities by Trachyspermum ammi Nanosuspensions.

Trachyspermum ammi is a frequently utilized traditional medicinal plant renowned for its pharmacological attributes, particularly in the realm of treating infectious diseases. This current study aims to comprehensively assess the in vitro properties of freshly prepared nanosuspensions derived from Trachyspermum ammi extracts, with a focus on their cost-effective potential in various areas, including antioxidant, antibacterial, cytotoxic, and antidiabetic activities. Biochemical characterization of T. ammi nanosuspensions by high-performance liquid chromatography (HPLC) and Fourier-transform infrared spectroscopy (FTIR) analyses. HPLC analysis revealed the presence of kaempferol and sinapic acid in various amounts at 11.5 ppm and 12.3 ppm, respectively. FTIR analysis of T. ammi powder revealed the presence of alcohols and amines. The assessment of antioxidant activity was conducted using a DPPH scavenging assay, indicating that the nanosuspensions exhibited their highest free radical scavenging activity, reaching 14.9%. Nanosuspensions showed 3.75 ± 3.529.5% biofilm inhibition activity against Escherichia coli. The antidiabetic activity was accessed through antiglycation and α- amylase inhibition assays, while nanosuspension showed the maximum inhibition activity at 25.35 ± 0.912133% and 34.6 ± 1.3675%. Hemolytic activity was also evaluated, and T. ammi nanosuspension showed 22.73 ± 1.539% hemolysis. This nanotechnology approach has established a foundation to produce plant-based nanosuspensions, offering a promising avenue for the biopharmaceutical production of herbal nanomedicines. These nanosuspensions have the potential to enhance bioavailability and can serve as a viable alternative to synthetic formulations.

The challenges to develop antibody-conjugated nanomedicine products

Nanomedicine becomes a key player especially as next generation medicine. Antibody-conjugated nanomedicine could significantly upgrade the treatment and expand application areas. However, there are extensive challenges of manufacturing those formulations as a final drug product. Here we provided the general technical guidance from the initial formulation construction including antibody conjugation to the downstream formulation development. We hope this technical note can help accelerate the translation of productizing the antibody-conjugated nanomedicines.

Feeding Next-Generation Nanomedicines to Europe: Regulatory and Quality Challenges.

New and innovative nanomedicines have been developed and marketed over the past half-century, revolutionizing the prognosis of many human diseases. Although a univocal regulatory definition is not yet available worldwide, the term "nanomedicines" generally identifies medicinal products that use nanotechnology in their design or production. Due to the intrinsic high structural complexity of these products, the scientific and regulatory communities are reflecting on how to revise the regulatory framework to provide a more appropriate benefit/risk balance to authorize them on the market, considering the impact of their peculiar physicochemical features in the evaluation of efficacy and safety patterns. Herein, a critical perspective is provided on the current open issues regarding regulatory qualification and physicochemical characterization of nanosystems considering the current European regulatory framework on nanomedicine products. Practicable paths for improving their quality assurance and predicting their fate in vivo are also argued. Strengthening the multilevel alliance among academic institutions, industrial stakeholders, and regulatory authorities seems strategic to support innovation by standard approaches (e.g., qualification, characterization, risk assessment), and to expand current knowledge, also benefiting from the new opportunities offered by artificial intelligence and digitization in predictive modelling of the impact of nanomedicine characteristics on their fate in vivo.

Current status and vision of local pharmaceutical industries in Saudi Arabia: The focus on nanomedicines

BackgroundPharmaceutical nanomedicine products are expected to impact the global pharmaceutical market and healthcare system significantly. Since 2000, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved over 80 nanomedicine products for marketing; an additional double that number is currently being tested in clinical trials. The nanomedicine market is expected to reach USD 350.8 billion by 2025 from USD 138.8 billion in 2016. This demonstrates the importance of nanotechnology to the delivery of pharmaceuticals. The main benefits of employing nanotechnology to distribute therapeutic agents include reducing the undesired toxicity from non-specific distribution and increasing patient adherence, which can indirectly minimize the burden on the country's healthcare system. Such products are expected to gain a significant economic impact on Saudi Arabia’s pharmaceutical drugs market once they get developed locally. MethodA descriptive and cross-sectional study, including a web-based questionnaire and a complete categorization of pharmaceutical products formed by the national industries in Saudi Arabia, was utilized to investigate the current and future direction of pharmaceutical manufacturing exploiting nanotechnology in the Kingdom. ResultsThe survey showed an apparent lack of willingness within the national pharmaceutical industries, as the majority (≈ 86%) of the leading Saudi companies cannot enable nanotechnology-based medicines in their manufacturing. However, more than 93% of the national pharmaceutical industries, upon the basis of the responses, agreed that the development of pharmaceutical products with nanotechnology is an important step toward solving various complications associated with conventional forms of the available medicine. ConclusionNational pharmaceutical industries in Saudi Arabia will need to get closer to manufacturing nanomedicines by partnering with international pioneer companies. In addition, empowering the local research and development (R&D) centers in nano delivery systems could facilitate translating their R&D outcomes into novel advanced and commercialized products. This could imitate the direction of the global pharmaceutical market and share its revenue which will positively reflect on the Kingdom's economy.

Drug-Grafted DNA for Cancer Therapy.

With the development of solid-phase synthesis and DNA nanotechnology, DNA-based drug delivery systems have seen large advancements over the past decades. By combining various drugs (small-molecular drugs, oligonucleotides, peptides, and proteins) with DNA technology, drug-grafted DNA has demonstrated great potential as a promising platform in recent years, in which complementary properties of both components have been discovered; for instance, the synthesis of amphiphilic drug-grafted DNA has enabled the production of DNA nanomedicines for gene therapy and chemotherapy. Through the design of linkages between drug and DNA parts, stimuli-responsiveness can be instilled, which has boosted the application of drug-grafted DNA in various biomedical applications such as cancer therapy. This review discusses the progress of various drug-grafted DNA therapeutic agents, exploring the synthetic techniques and anticancer applications afforded through the combination of drug and nucleic acids.

Scale-up challenges in the production of nanomedicines from lab to industry

Scale-up challenges in the production of nanomedicines from lab to industry

An Overview of Nanoparticle Protein Corona Literature.

The protein corona forms spontaneously on nanoparticle surfaces when nanomaterials are introduced into any biological system/fluid. Reliable characterization of the protein corona is, therefore, a vital step in the development of safe and efficient diagnostic and therapeutic nanomedicine products. 2134 published manuscripts on the protein corona are reviewed and a down-selection of 470 papers spanning 2000-2021, comprising 1702 nanoparticle (NP) systems is analyzed. This analysis reveals: i) most corona studies have been conducted on metal and metal oxide nanoparticles; ii) despite their overwhelming presence in clinical practice, lipid-based NPs are underrepresented in protein corona research, iii) studies use new methods to improve reliability and reproducibility in protein corona research; iv) studies use more specific protein sources toward personalized medicine; and v) careful characterization of nanoparticles after corona formation is imperative to minimize the role of aggregation and protein contamination on corona outcomes. As nanoparticles used in biomedicine become increasingly prevalent and biochemically complex, the field of protein corona research will need to focus on developing analytical approaches and characterization techniques appropriate for each unique nanoparticle formulation. Achieving such characterization of the nano-bio interface of nanobiotechnologies will enable more seamless development and safe implementation of nanoparticles in medicine.

The Regulatory Landscape of New Health Technologies and Nanotechnologies: The Role of Complexity of Nanosystems.

Herein we present the modern issue of new health technologies that emerge in Medicine and Therapeutics, with regard to their development, regulatory framework, approval, and post-approval monitoring. The European law and legislation distinguish the various subcategories of health technologies in medicinal products, medical devices, biotechnological products, advanced therapy medicinal products, and nanomedicinal products. Each of these categories presents its own distinctive characteristics, based on principles that regard the development technology and intended therapeutic use, and, as a result, is defined by a unique regulatory framework inside the European legislation environment. New health technologies are a key of twenty-first-century knowledge, science, and economy and a part of society growth and economic development, while at the same time they present significant challenges, mainly through matters that regard their safety, efficacy, and value for the public. In this environment, the concept of complexity of living and artificial systems arises, as part of their nature, but also as a perspective that will give answers regarding their dynamic behavior, evolution, and overall quality.

"Pejzažni" prikaz nanolekova - ekspertska perspektiva

The field of nanotechnology is at the forefront of a scientific revolution, where the term "nano" transcends mere size and opens the door to enormous possibilities. In the context of drug development, the selection of a suitable drug delivery system (corresponding to a certain active pharmaceutical ingredient) is a pivotal decision. Accordingly, nanosystems have emerged as a promising avenue, offering innovative solutions, and gaining recognition for addressing healthcare issues. While these products hold immense promise, they have faced certain complexities in their translation from the preclinical to the clinical setting, reflected in the lack of proper assessment protocols for quality and safety aspects and, consequently, an insufficiently defined regulatory environment. Since the groundbreaking US Food and Drug Administration (FDA) approval of liposomal doxorubicin in 1995, approximately 80 nanomedicine products have received regulatory approval so far. Recent attention has gravitated toward lipid-based nanomedicines, particularly in the development of mRNA vaccines during the COVID-19 pandemic, further highlighting their significance. However, the relatively modest number of approved nanomedicines compared to the extensive research efforts raises important questions and underscores areas of uncertainty. This article provides an overview of the challenges in defining nanomedicines, their properties, the complexities of regulatory frameworks, and the imperative for standardized characterization protocols.

Biophysical interactions of mixed lipid-polymer nanoparticles incorporating curcumin: Potential as antibacterial agent

The technology of lipid nanoparticles has a long history in drug delivery, which begins with the discovery of liposomes by Alec D Bangham in the 1960s. Since then, numerous studies have been conducted on these systems, and several nanomedicinal products that utilize them have entered the market, with the latest being the COVID-19 vaccines. Despite their success, many aspects of their biophysical behavior are still under investigation. At the same time, their combination with other classes of biomaterials to create more advanced platforms is a promising endeavor. Herein, we developed mixed lipid-polymer nanoparticles with incorporated curcumin as a drug delivery system for therapy, and we studied its interactions with various biosystems. Initially, the nanoparticle physicochemical properties were investigated, where their size, size distribution, surface charge, morphology, drug incorporation and stability were assessed. The incorporation of the drug molecule was approximately 99.8 % for a formulated amount of 10 % by weight of the total membrane components and stable in due time. The association of the nanoparticles with human serum albumin and the effect that this brings upon their properties was studied by several biophysical techniques, including light scattering, thermal analysis and circular dichroism. As a biocompatibility assessment, interactions with erythrocyte membranes and hemolysis induced by the nanoparticles were also studied, with empty nanoparticles being more toxic than drug-loaded ones at high concentrations. Finally, interactions with bacterial membrane proteins of Staphylococcus aureus and the antibacterial effect of the nanoparticles were evaluated, where the effect of curcumin was improved when incorporated inside the nanoparticles. Overall, the developed mixed nanoparticles are promising candidates for the delivery of curcumin to infectious and other types of diseases.

Sex-Specific Silica Nanoparticle Protein Corona Compositions Exposed to Male and Female BALB/c Mice Plasmas.

As various nanoparticles (NPs) are increasingly being used in nanomedicine products for more effective and less toxic therapy and diagnosis of diseases, there is a growing need to understand their biological fate in different sexes. Herein, we report a proof-of-concept result of sex-specific protein corona compositions on the surface of silica NPs as a function of their size and porosity upon incubation with plasma proteins of female and male BALB/c mice. Our results demonstrate substantial differences between male and female protein corona profiles on the surface of silica nanoparticles. By comparing protein abundances between male and female protein coronas of mesoporous silica nanoparticles and Stöber silica nanoparticles of ∼100, 50, and 100 nm in diameter, respectively, we detected 17, 4, and 4 distinct proteins, respectively, that were found at significantly different concentrations for these constructs. These initial findings demonstrate that animal sex can influence protein corona formation on silica NPs as a function of the physicochemical properties. A more thorough consideration of the role of plasma sex would enable nanomedicine community to design and develop safer and more efficient diagnostic and therapeutic nanomedicine products for both sexes.

The Application of Light-Assisted Drying to the Thermal Stabilization of Nucleic Acid Nanoparticles.

Background: Cold-chain storage can be challenging and expensive for the transportation and storage of biologics, especially in low-resource settings. Nucleic acid nanoparticles (NANPs) are an example of new biological products that require refrigerated storage. Light-assisted drying (LAD) is a new processing technique to prepare biologics for anhydrous storage in a trehalose amorphous solid matrix at ambient temperatures. In this study, LAD was used to thermally stabilize four types of NANPs with differing structures and melting temperatures. Methods: Small volume samples (10 μL) containing NANPs were irradiated with a 1064 nm laser to speed the evaporation of water and create an amorphous trehalose preservation matrix. Samples were then stored for 1 month at 4°C or 20°C. A FLIR C655 mid-IR camera was used to record the temperature of samples during processing. The trehalose matrix was characterized using polarized light imaging (PLI) to determine if crystallization occurred during processing or storage. Damage to LAD-processed NANPs was assessed after processing and storage using gel electrophoresis. Results: Based on the end moisture content (EMC) as a function time and the thermal histories of samples, a LAD processing time of 30 min is sufficient to achieve low EMCs for the 10 μL samples used in this study. PLI demonstrates that the trehalose matrix was resistant to crystallization during processing and after storage at 4°C and at room temperature. The native-polyacrylamide gel electrophoresis results for DNA cubes, RNA cubes, and RNA rings indicate that the main structures of these NANPs were not damaged significantly after LAD processing and being stored at 4°C or at room temperature for 1 month. Conclusions: These preliminary studies indicate that LAD processing can stabilize NANPs for dry-state storage at room temperature, providing an alternative to refrigerated storage for these nanomedicine products.

FRET as the tool for in vivo nanomedicine tracking.

Advanced drug delivery system utilizing a nanocarrier is the major application of nanotechnology on pharmacotherapeutics. However, despite the promising benefits and a leading trend in pharmaceutical research, nanomedicine development suffers from a poor clinical translation problem as only a handful of nanomedicine products reach the market yearly. The conventional pharmacokinetic study generally focuses only on monitoring the level of a free drug but ignores the nanocarrier's role in pharmacokinetics. One hurdle is that it is difficult to directly track intact nanocarriers in vivo to explore their pharmacokinetics. Although several imaging techniques such as radiolabeling, nuclear imaging, fluorescence imaging, etc., have been developed over the past few years, currently, one method that can successfully track the intact nanocarriers in vivo directly is by Förster resonance energy transfer (FRET). This review summarizes the application of FRET as the in vivo nanoparticle tracker for studying the in vivo pharmacokinetics of the organic nanocarriers and gives elaborative details on the techniques utilized.