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The blood‐brain barrier (BBB) poses a significant challenge in delivering therapeutic agents for brain diseases due to its high selectivity against foreign substances. This limitation greatly hampers the effectiveness of conventional chemotherapeutic drugs in treating brain cancers. In response, lipid‐based nanoparticles (LNPs) have emerged as a promising approach, offering opportunities for targeted drug delivery by conjugating targeting ligands onto their surface. This review provides a comprehensive overview of recent advancements in utilizing LNPs to traverse the BBB for enhanced transport of bioactive compounds into the brain, specifically for cancer treatments. Beginning with an exploration of the biological structure and functions of the BBB and the blood‐brain tumor barrier (BBTB), the review highlights the advantages presented by LNPs. Subsequently, it delves into strategies for surface modification of nanoparticles to enhance BBB targeting and improve efficacy in brain cancer treatment. Finally, the review offers insights into future prospects for designing the next generation of LNPs. The review presented herein aims to contribute to the ongoing efforts in overcoming the challenges associated with BBB penetration, ultimately advancing therapeutic strategies for brain cancer and other neurological disorders. [ABSTRACT FROM AUTHOR]

Mathematical modeling of drug release from drug delivery systems is crucial for understanding and optimizing formulations. This research provides a comparative mathematical analysis of drug release from lipid-based nanoparticles. Drug release profiles from various types of lipid nanoparticles, including liposomes, nanostructured lipid carriers (NLCs), solid lipid nanoparticles (SLNs), and nano/micro-emulsions (NEMs/MEMs), were extracted from the literature and used to assess the suitability of eight conventional mathematical release models. For each dataset, several metrics were calculated, including the coefficient of determination (R2), adjusted R2, the number of errors below certain thresholds (5%, 10%, 12%, and 20%), Akaike information criterion (AIC), regression sum square (RSS), regression mean square (RMS), residual sum of square (rSS), and residual mean square (rMS). The Korsmeyer-Peppas model ranked highest among the evaluated models, with the highest adjusted R2 values of 0.95 for NLCs and 0.93 for other liposomal drug delivery systems. The Weibull model ranked second, with adjusted R2 values of 0.92 for liposomal systems, 0.94 for SLNs, and 0.82 for NEMs/MEMs. Thus, these two models appear to be more effective in forecasting and characterizing the release of lipid nanoparticle drugs, potentially making them more suitable for upcoming research endeavors. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is a highly malignant and invasive tumor with significant mortality and morbidity. Current treatment modalities such as surgery, radiotherapy, and chemotherapy encounter significant limitations, such as poor targeting, systemic toxicity, and drug resistance. There is an urgent need for novel therapeutic strategies that offer targeted delivery, enhanced efficacy, and reduced side effects. The advent of lipid-based nanoparticles (LNPs) offers a promising tool for OSCC therapy, potentially overcoming the limitations of current therapeutic approaches. LNPs are composed of biodegradable and biocompatible lipids, which minimize the risk of toxicity and adverse effects. LNPs can encapsulate hydrophobic drugs, improving their solubility and stability in the biological environment, thereby enhancing their bioavailability. LNPs demonstrate significantly higher ability to encapsulate lipophilic drugs than other nanoparticle types. LNPs offer excellent storage stability, minimal drug leakage, and controlled drug release, making them highly effective nanoplatforms for the delivery of chemotherapeutic agents. Additionally, LNPs can be modified by complexing them with specific target ligands on their surface. This surface modification allows the active targeting of LNPs to the tumors in addition to the passive targeting mechanism. Furthermore, the PEGylation of LNPs improves their hydrophilicity and enhances their biological half-life by reducing clearance by the reticuloendothelial system. This review aims to discuss current treatment approaches and their limitations, as well as recent advancements in LNPs for better management of OSCC.

Kittipat Suwanpitak,1 Kampanart Huanbutta,2 Nopphon Weeranoppanant,3 Pornsak Sriamornsak,4,5 Chonlada Panpipat,1 Tanikan Sangnim1 1Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, 20131, Thailand; 2Department of Manufacturing Pharmacy, College of Pharmacy, Rangsit University, Pathum Thani, 12000, Thailand; 3Department of Chemical Engineering, Faculty of Engineering, Burapha University, Chonburi, 20131, Thailand; 4Department of Industrial Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand; 5Academy of Science, the Royal Society of Thailand, Bangkok, 10300, ThailandCorrespondence: Tanikan Sangnim, Faculty of Pharmaceutical Sciences, Burapha University, 169, Seansook, Muang, Chonburi, 20131, Thailand, Email tanikan@go.buu.ac.thIntroduction: Lipid-based nanoparticles (LNPs) is increasingly recognized for their potential in drug delivery, offering protection to hydrophobic drugs from degradation. Industrial synthesis of LNPs, exemplified by Pfizer-BioNTech and Moderna mRNA vaccines, utilizes flow chemistry or microfluidics, showcasing its scalability. This study explores the utilization of a novel design reactor, the vortex tube reactor, within flow chemistry for LNPs synthesis, aiming to optimize its conditions and compare them with batch synthesis.Methods: LNPs were synthesized using the vortex tube reactor, incorporating bovine serum albumin (BSA) as a model drug in the aqueous phase, alongside 1.2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol in the organic phase. Design of experiments (DoE), specifically Box-Behnken design, was employed to optimize parameters, including X1: the flow rate ratio (10– 100 mL/min), X2: the aqueous-to-organic volumetric ratio (1:1– 10:1), and X3: the number of reactor units (1– 5 units). Responses evaluated encompassed physical properties and productivity. Optimized conditions were determined by minimizing particle size (Y1), polydispersity index (Y2), and zeta potential (Y3), while maximizing entrapment efficiency (Y4), drug loading (Y5), and productivity (Y5).Results: Results indicated that optimal conditions were achieved at X1 of 100 mL/min, X2 of 5.278, and X3 of 1 unit. LNPs synthesized under these conditions exhibited favorable physical properties and productivity, with uniformity maintained across batches. The vortex tube reactor demonstrated superiority over batch synthesis, yielding smaller particles (166.23 ± 0.98 nm), more uniform nanoparticles (PDI 0.17 ± 0.01), and higher entrapment (67.75 ± 1.55%) and loading capacities (36.39 ± 0.83%), indicative of enhanced productivity (313.4 ± 12.88 mg/min).Conclusion: This study elucidates the potential of flow chemistry, particularly utilizing the vortex tube reactor, for large-scale LNPs formulation, offering insights into parameter relationships and advancing nanoparticle synthesis for drug delivery applications. Keywords: flow chemistry, lipid-based nanoparticles, nanoparticles synthesis, biological product

Immunotherapy combined with chemicals and genetic engineering tools is emerging as a promising strategy to treat triple-negative breast cancer (TNBC), which is more aggressive with poorer progress than other breast cancer subtypes. In this study, lipid-based nanoparticles (LNPs) possessed an NK cell-like function that could deliver tumor-specific therapeutics and inhibit tumor growth. LNPs fused with an NK cell membrane protein system (NK-LNP) have three main features: (i) hydrophilic plasmid DNA can inhibit TNBC metastasis when encapsulated within LNPs and delivered to cells; (ii) the lipid composition of LNPs, including C18 ceramide, exhibits anticancer effects; (iii) NK cell membrane proteins are immobilized on the LNP surface, enabling targeted delivery to TNBC cells. These particles facilitate the targeted delivery of HIC1 plasmid DNA and the modulation of immune cell functions. Delivered therapeutic genes can inhibit metastasis of TNBC and then induce apoptotic cell death while targeting macrophages to promote cytokine release. The anticancer effect is expected to be applied in treating various difficult-to-treat cancers with LNP fused with NK cell plasma membrane proteins, which can simultaneously deliver therapeutic chemicals and genes. [ABSTRACT FROM AUTHOR]

Liver cancer, specifically hepatocellular carcinoma (HCC), is the second leading cause of cancer-related deaths, following pancreatic cancer. The 5-year overall survival rate for HCC remains relatively low. Currently, there are multiple treatment options available for HCC, including systemic drugs, minimally invasive local therapies such as radiofrequency ablation, transarterial chemoembolization (TACE), and arterial radioembolization (TARE), as well as surgical interventions like liver resection or transplantation. However, the effectiveness of drug delivery to the cancerous liver is hindered by pathophysiological changes in the organ. In order to address this challenge, lipid-based nanoparticles (LNPs) have emerged as promising platforms for delivering a diverse range of therapeutic drugs. LNPs offer various structural configurations that enhance their physical stability and enable them to accommodate different types of cargo with varying mechanical properties and degrees of hydrophobicity. In this article, we provide a comprehensive review of the current applications of LNPs in the development of anti-HCC therapies. By examining the existing research, we aim to shed light on the potential future directions and advancements in this field. [ABSTRACT FROM AUTHOR]

Nanotechnology has emerged as a transformative force in the field of vaccine delivery, offering innovative solutions to enhance immunogenicity and efficacy. This review explores the integration of nanotechnology in vaccine development, emphasizing its role in addressing the limitations of traditional vaccines. Nanoparticles, including lipid-based, polymer-based, inorganic nanoparticles and virus-like particles, provide targeted delivery and controlled release of antigens, improving vaccine stability and uptake by immune cells. These nanosystems also possess inherent adjuvant properties, enhancing antigen presentation and activation of immune responses. Notable case studies, such as mRNA vaccines for COVID-19, demonstrate the successful application of lipid nanoparticles in inducing robust immune responses. Additionally, clinical trials reveal the comparative efficacy of nanoparticle-based vaccines over conventional counterparts. Despite the promising advancements, challenges related to safety, biocompatibility, regulatory approval and manufacturing scalability persist. Future directions highlight the potential of emerging nanomaterials and personalized vaccine approaches in revolutionizing global health. The adoption of nanotechnology in vaccine delivery systems holds the promise of more effective, accessible and affordable vaccines, ultimately contributing to improved public health outcomes worldwide. [ABSTRACT FROM AUTHOR]

With its unique properties and potential applications, nanoparticle-based delivery platforms for messenger RNA (mRNA) vaccines have gained significant attention in recent years. Nanoparticles have the advantages of enhancing immunogenicity, targeting delivery, and improving stability, providing a new solution for drug and vaccine delivery. In some clinical studies, a variety of nanoparticle delivery platforms have been gradually applied to a wide range of vaccine applications. Current research priorities are exploring various types of nanoparticles as vaccine delivery systems to enhance vaccine stability and immunogenicity. Lipid nanoparticles (LNPs) have shown promising potential in preclinical and clinical studies on the efficient delivery of antigens to immune cells. Moreover, lipid nanoparticles and other nanoparticles for nucleic acids, especially for mRNA delivery systems, have shown vast potential for vaccine development. In this review, we present various vaccine platforms with an emphasis on nanoparticles as mRNA vaccine delivery vehicles. We describe several novel nanoparticle delivery platforms for mRNA vaccines, such as lipid-, polymer-, and protein-based nanoparticles. In addition, we provide an overview of the anti-tumor immunity of nanovaccines against different tumors in cancer immunotherapy. Finally, we outline future perspectives and remaining challenges for this promising technology of nanoparticle-based delivery platforms for vaccines. [ABSTRACT FROM AUTHOR]

Due to its cost-effectiveness, convenience, and high patient adherence, oral drug administration normally remains the preferred approach. Yet, the effective delivery of hydrophobic drugs via the oral route is often hindered by their limited water solubility and first-pass metabolism. To mitigate these challenges, advanced delivery systems such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been developed to encapsulate hydrophobic drugs and enhance their bioavailability. However, traditional design methodologies for these complex formulations often present intricate challenges because they are restricted to a relatively narrow design space. Here, we present a data-driven approach for the accelerated design of SLNs/NLCs encapsulating a model hydrophobic drug, cannabidiol, that combines experimental automation and machine learning. A small subset of formulations, comprising 10% of all formulations in the design space, was prepared in-house, leveraging miniaturized experimental automation to improve throughput and decrease the quantity of drug and materials required. Machine learning models were then trained on the data generated from these formulations and used to predict properties of all SLNs/NLCs within this design space (i.e., 1215 formulations). Notably, formulations predicted to be high-performers via this approach were confirmed to significantly enhance the solubility of the drug by up to 3000-fold and prevented degradation of drug. Moreover, the high-performance formulations significantly enhanced the oral bioavailability of the drug compared to both its free form and an over-the-counter version. Furthermore, this bioavailability matched that of a formulation equivalent in composition to the FDA-approved product, Epidiolex®. [ABSTRACT FROM AUTHOR]

Metronidazole (MTZ) is a vital antimicrobial agent widely used in the treatment of various infections. However, its limited bioavailability and associated side effects necessitate the development of efficient drug delivery systems to enhance therapeutic efficacy and minimize adverse reactions. The field of nanotechnology and nanomaterials presents promising solutions for delivering MTZ, leveraging their unique properties to overcome these challenges. This comprehensive review explores a variety of nanomaterial-based approaches for MTZ delivery, emphasizing the benefits such as improved drug stability, targeted release, and enhanced bioavailability. Various nanocarrier systems, including polymeric nanoparticles, lipid-based nanocarriers, and inorganic nanoparticles, are evaluated for their potential in MTZ delivery applications. The review underscores strategies aimed at reducing MTZ's side effects through controlled release and targeted delivery, with nanocarriers facilitating sustained drug release to minimize fluctuations in drug concentrations and potentially mitigate adverse reactions linked to MTZ administration. Furthermore, innovative combination therapies involving MTZ and other drugs are investigated for their ability to enhance therapeutic outcomes and combat drug resistance. Co-delivery systems show promise in synergistically targeting infections while reducing overall dosage and associated side effects. By summarizing the latest advancements in MTZ delivery, this review provides valuable insights into the potential of nanotechnology-based strategies for optimizing MTZ therapy. These approaches have the potential to transform drug delivery, offering safer and more effective treatments for infectious diseases, and improving patient outcomes by reducing adverse effects.

Cancer is a complex heterogeneous disease that poses a significant public health challenge. In recent years, lipid-based nanoparticles (LBNPs) have expanded drug delivery and vaccine development options owing to their adaptable, non-toxic, tuneable physicochemical properties, versatile surface functionalisation, and biocompatibility. LBNPs are tiny artificial structures composed of lipid-like materials that can be engineered to encapsulate and deliver therapeutic agents with pinpoint accuracy. They have been widely explored in oncology; however, our understanding of their pharmacological mechanisms, effects of their composition, charge, and size on cellular uptake, tumour penetration, and how they can be utilised to develop cancer vaccines is still limited. Hence, we reviewed LBNPs' unique characteristics, biochemical features, and tumour-targeting mechanisms. Furthermore, we examined their ability to enhance cancer therapies and their potential contribution in developing anticancer vaccines. We critically analysed their advantages and challenges impeding swift advancements in oncology and highlighted promising avenues for future research. LBNPs are tiny artificial particles made of lipids using different formulation methods. They are powerful and versatile delivery platforms with great potential as anticancer therapies. LBNPs have been tested in clinical applications and can safely deliver anticancer agents, including vaccine payloads designed to target various cancer types. LBNPs' size, surface charge, and targeting ligands can be modified during formulation, and they can be administered to specific tissues via various routes. LBNPs can target tumours and release their payload via active, passive, or stimuli-responsive mechanisms. Active targeting requires surface modification in order to target and deliver their payload, while passive targeting do not. Stimuli-responsive release mechanisms move to the tumour microenvironment and release their payload upon an internal or external stimulus. There are several challenges faced by LBNPs in delivering cancer drugs and vaccines, but advanced research methods have opened new doors vital for expanding their applications in clinical oncology. LBNPs offer the advantage of enhanced drug stability and bioavailability, prolonged circulation time of therapeutic agents in the bloodstream, and improved efficacy in targeting cancerous tissues. [ABSTRACT FROM AUTHOR]

Cancer is a severe disease that results in death in all countries of the world. A nano-based drug delivery approach is the best alternative, directly targeting cancer tumor cells with improved drug cellular uptake. Different types of nanoparticle-based drug carriers are advanced for the treatment of cancer, and to increase the therapeutic effectiveness and safety of cancer therapy, many substances have been looked into as drug carriers. Lipid-based nanoparticles (LBNPs) have significantly attracted interest recently. These natural biomolecules that alternate to other polymers are frequently recycled in medicine due to their amphipathic properties. Lipid nanoparticles typically provide a variety of benefits, including biocompatibility and biodegradability. This review covers different classes of LBNPs, including their characterization and different synthesis technologies. This review discusses the most significant advancements in lipid nanoparticle technology and their use in medicine administration. Moreover, the review also emphasized the applications of lipid nanoparticles that are used in different cancer treatment types. [ABSTRACT FROM AUTHOR]

Since the first use of vaccine tell the last COVID-19 pandemic caused by spread of SARS-CoV-2 worldwide, the use of advanced biotechnological techniques has accelerated the development of different types and methods for immunization. The last pandemic showed that the nucleic acid-based vaccine, especially mRNA, has an advantage in terms of development time; however, it showed a very critical drawback namely, the higher costs when compared to other strategies, and its inability to protect against new variants. This showed the need of more improvement to reach a better delivery and efficacy. In this review we will describe different vaccine delivery systems including, the most used viral vector, and also variable strategies for delivering of nucleic acid-based vaccines especially lipid-based nanoparticles formulation, polymersomes, electroporation and also the new powerful tools for the delivery of mRNA, which is based on the use of cell-penetrating peptides (CPPs). Additionally, we will also discuss the main challenges associated with each system. Finlay, the efficacy and safety of the vaccines depends not only on the formulations and delivery systems, but also the dosage and route of administration are also important players, therefore we will see the different routes for the vaccine administration including traditionally routes (intramuscular, Transdermal, subcutaneous), oral inhalation or via nasal mucosa, and will describe the advantages and disadvantage of each administration route.

Neurodegenerative diseases, such as Alzheimer's and Parkinson's, affect a wide variety of the population and pose significant challenges with progressive and irreversible neural cell loss. The limitations of brain-targeting therapies and the unclear molecular mechanisms driving neurodegeneration hamper the possibility of developing successful treatment options. Thus, nanoscale drug delivery platforms offer a promising solution. This paper explores and compares lipidic nanoparticles, extracellular vesicles (EVs), and hybrid liposomal–EV nanoplatforms as advanced approaches for targeted delivery to combat neurodegeneration. Lipidic nanoparticles are well-characterized platforms that allow multi-drug loading and scalable production. Conversely, EVs offer the ability of selectively targeting specific tissues and high biocompatibility. The combination of these two platforms in one could lead to promising results in the treatment of neurodegeneration. However, many issues, such as the regulatory framework, remain to be solved before these novel products are translated into clinical practice. [ABSTRACT FROM AUTHOR]

In recent years, due to their distinctive and adaptable therapeutic effects, many natural bioactive compounds have been commonly used to treat diseases. Their limited solubility, low bioavailability, inadequate gastrointestinal tract stability, high metabolic rate, and shorter duration of action limited their pharmaceutical applications. However, those can be improved using nanotechnology to create various drug delivery systems, including lipid-based nanoparticles, to adjust the compounds' physicochemical properties and pharmacokinetic profile. Because of the enormous technical advancements made in the fundamental sciences and the physical and chemical manipulation of individual atoms and molecules, the subject of nanotechnology has experienced revolutionary growth. By fabricating certain functionalized particles, nanotechnology opens an innovative horizon in research and development for overcoming restrictions, including traditional medication administration systems. Nanotechnology-driven bioactive compounds are certain to have a high impact and clinical value for current and future uses. Lipid-based nanotechnologies were shown to deliver a range of naturally occurring bioactive compounds with decent entrapment potential and stability, a successfully controlled release, increased bioavailability, and intriguing therapeutic activity. This review outlines bioactive compounds such as paclitaxel, curcumin, rhodomyrtone, quercetin, kaempferol, resveratrol, epigallocatechin-3-gallate, silymarin, and oridonin, fortified within either a natural or synthetic lipid-based drug delivery system based on nanotechnology and their evaluation and clinical considerations. [ABSTRACT FROM AUTHOR]

The application of lipid‐based nanoparticles for COVID‐19 vaccines and transthyretin‐mediated amyloidosis treatment have highlighted their potential for translation to cancer therapy. However, their use in delivering drugs to solid tumors is limited by ineffective targeting, heterogeneous organ distribution, systemic inflammatory responses, and insufficient drug accumulation at the tumor. Instead, the use of lipid‐based nanoparticles to remotely activate immune system responses is an emerging effective strategy. Despite this approach showing potential for treating hematological cancers, its application to treat solid tumors is hampered by the selection of eligible targets, tumor heterogeneity, and ineffective penetration of activated T cells within the tumor. Notwithstanding, the use of lipid‐based nanoparticles for immunotherapy is projected to revolutionize cancer therapy, with the ultimate goal of rendering cancer a chronic disease. However, the translational success is likely to depend on the use of predictive tumor models in preclinical studies, simulating the complexity of the tumor microenvironment (e.g., the fibrotic extracellular matrix that impairs therapeutic outcomes) and stimulating tumor progression. This review compiles recent advances in the field of antitumor lipid‐based nanoparticles and highlights emerging therapeutic approaches (e.g., mechanotherapy) to modulate tumor stiffness and improve T cell infiltration, and the use of organoids to better guide therapeutic outcomes. [ABSTRACT FROM AUTHOR]

[Display omitted] The aim of the study was to evaluate the effect of thiolation of lipid-based nanoparticles (LNPs) on cellular uptake of nucleic acids. A thiolated surfactant was synthesized by binding palmitic acid covalently to cysteine. Green fluorescent protein (GFP) encoding plasmid DNA (pDNA) was used as model nucleic acid and incorporated via hydrophobic ion-pairing with a cationic cholesterol derivate (DcCholesterol) in LNPs that were prepared by solvent injection method using the thiolated surfactant for surface decoration. LNPs were characterized regarding size, polydispersity index, zeta potential and stability in biorelevant media. The endosomal escape properties of LNPs were evaluated by erythrocytes interaction studies. Cell viability and transfection efficiency on HEK293 cells were investigated. The structure of the thiolated surfactant was confirmed by 1H NMR and FT-IR. LNPs containing the nucleic acid-DcCholesterol complex with and without the thiolated surfactant were developed and displayed sizes in the range from 173 nm to 233 nm with a narrow size distribution (PDI < 0.3) and a negative zeta potential. LNPs showed no significant increase in size after 4 h of incubation in artificial body fluids. Erythrocytes interaction studies revealed enhanced endosomal escape properties for thiolated LNPs compared to non-thiolated LNPs. LNPs showed in concentrations lower than 0.74 mg/mL cell viability ≥ 80 %. Transfection studies on HEK cells with thiolated LNPs compared to non-thiolated LNP showed a 4.6-fold higher expression of GFP. Surface thiolation of LNPs represents a promising tool for enhancing intracellular nucleic acid delivery of LNPs. [ABSTRACT FROM AUTHOR]

Infectious diseases are a predominant problem in human health. While the incidence of many pathogenic infections is controlled by vaccines, some pathogens still pose a challenging task for vaccine researchers. In order to face these challenges, the field of vaccine development has changed tremendously over the last few years. For non-replicating recombinant antigens, novel vaccine delivery systems that attempt to increase the immunogenicity by mimicking structural properties of pathogens are already approved for clinical applications. Lipid-based nanoparticles (LbNPs) of different natures are vesicles made of lipid layers with aqueous cavities, which may carry antigens and other biomolecules either displayed on the surface or encapsulated in the cavity. However, the efficacy profile of recombinant LbNP vaccines is not as high as that of live-attenuated ones. This review gives a compendious picture of two approaches that affect the immunogenicity of recombinant LbNP vaccines: (i) the incorporation of immunostimulatory agents and (ii) the utilization of pre-existing or promiscuous cellular immunity, which might be beneficial for the development of tailored prophylactic and therapeutic LbNP vaccine candidates. [ABSTRACT FROM AUTHOR]

Cancer is a severe disease that results in death in all countries of the world. A nano-based drug delivery approach is the best alternative, directly targeting cancer tumor cells with improved drug cellular uptake. Different types of nanoparticle-based drug carriers are advanced for the treatment of cancer, and to increase the therapeutic effectiveness and safety of cancer therapy, many substances have been looked into as drug carriers. Lipid-based nanoparticles (LBNPs) have significantly attracted interest recently. These natural biomolecules that alternate to other polymers are frequently recycled in medicine due to their amphipathic properties. Lipid nanoparticles typically provide a variety of benefits, including biocompatibility and biodegradability. This review covers different classes of LBNPs, including their characterization and different synthesis technologies. This review discusses the most significant advancements in lipid nanoparticle technology and their use in medicine administration. Moreover, the review also emphasized the applications of lipid nanoparticles that are used in different cancer treatment types.

In recent years, the field of drug delivery has seen a significant shift towards the exploration and utilization of nanoparticles (NPs) as versatile carriers for therapeutic agents. With its ability to provide exact control over NPs’ characteristics, microfluidics has emerged as a potent platform for the efficient and controlled synthesis of NPs. Microfluidic devices designed for precise fluid manipulation at the micro-scale offer a unique platform for tailoring NP properties, enabling enhanced control over NP properties such as size, morphology, and size distribution while ensuring high batch-to-batch reproducibility. Microfluidics can be used to produce liposomes, solid lipid nanoparticles, polymer-based NPs, and lipid-polymer hybrid NPs, as well as a variety of inorganic NPs such as silica, metal, metal oxide, quantum dots, and carbon-based NPs, offering precise control over composition and surface properties. Its unique precision in tailoring NP properties holds great promise for advancing NP-based drug delivery systems in both clinical and industrial settings. Although challenges with large-scale production still remain, microfluidics offers a transformative approach to NP synthesis. In this review, starting from the historical development of microfluidic systems, the materials used to create the systems, microfabrication methods, and system components will be discussed in order to provide the reader with an overview of microfluidic systems. In the following, studies on the fabrication of nanoparticles such as lipid NPs, polymeric NPs, and inorganic NPs in microfluidic devices are included.

Immunotherapy combined with chemicals and genetic engineering tools is emerging as a promising strategy to treat triple-negative breast cancer (TNBC), which is more aggressive with poorer progress than other breast cancer subtypes. In this study, lipid-based nanoparticles (LNPs) possessed an NK cell-like function that could deliver tumor-specific therapeutics and inhibit tumor growth. LNPs fused with an NK cell membrane protein system (NK-LNP) have three main features: (i) hydrophilic plasmid DNA can inhibit TNBC metastasis when encapsulated within LNPs and delivered to cells; (ii) the lipid composition of LNPs, including C18 ceramide, exhibits anticancer effects; (iii) NK cell membrane proteins are immobilized on the LNP surface, enabling targeted delivery to TNBC cells. These particles facilitate the targeted delivery of HIC1 plasmid DNA and the modulation of immune cell functions. Delivered therapeutic genes can inhibit metastasis of TNBC and then induce apoptotic cell death while targeting macrophages to promote cytokine release. The anticancer effect is expected to be applied in treating various difficult-to-treat cancers with LNP fused with NK cell plasma membrane proteins, which can simultaneously deliver therapeutic chemicals and genes.

Abstract The application of lipid‐based nanoparticles for COVID‐19 vaccines and transthyretin‐mediated amyloidosis treatment have highlighted their potential for translation to cancer therapy. However, their use in delivering drugs to solid tumors is limited by ineffective targeting, heterogeneous organ distribution, systemic inflammatory responses, and insufficient drug accumulation at the tumor. Instead, the use of lipid‐based nanoparticles to remotely activate immune system responses is an emerging effective strategy. Despite this approach showing potential for treating hematological cancers, its application to treat solid tumors is hampered by the selection of eligible targets, tumor heterogeneity, and ineffective penetration of activated T cells within the tumor. Notwithstanding, the use of lipid‐based nanoparticles for immunotherapy is projected to revolutionize cancer therapy, with the ultimate goal of rendering cancer a chronic disease. However, the translational success is likely to depend on the use of predictive tumor models in preclinical studies, simulating the complexity of the tumor microenvironment (e.g., the fibrotic extracellular matrix that impairs therapeutic outcomes) and stimulating tumor progression. This review compiles recent advances in the field of antitumor lipid‐based nanoparticles and highlights emerging therapeutic approaches (e.g., mechanotherapy) to modulate tumor stiffness and improve T cell infiltration, and the use of organoids to better guide therapeutic outcomes.

In recent years, the field of drug delivery has seen a significant shift towards the exploration and utilization of nanoparticles (NPs) as versatile carriers for therapeutic agents. With its ability to provide exact control over NPs' characteristics, microfluidics has emerged as a potent platform for the efficient and controlled synthesis of NPs. Microfluidic devices designed for precise fluid manipulation at the micro-scale offer a unique platform for tailoring NP properties, enabling enhanced control over NP properties such as size, morphology, and size distribution while ensuring high batch-to-batch reproducibility. Microfluidics can be used to produce liposomes, solid lipid nanoparticles, polymer-based NPs, and lipid-polymer hybrid NPs, as well as a variety of inorganic NPs such as silica, metal, metal oxide, quantum dots, and carbon-based NPs, offering precise control over composition and surface properties. Its unique precision in tailoring NP properties holds great promise for advancing NP-based drug delivery systems in both clinical and industrial settings. Although challenges with large-scale production still remain, microfluidics offers a transformative approach to NP synthesis. In this review, starting from the historical development of microfluidic systems, the materials used to create the systems, microfabrication methods, and system components will be discussed in order to provide the reader with an overview of microfluidic systems. In the following, studies on the fabrication of nanoparticles such as lipid NPs, polymeric NPs, and inorganic NPs in microfluidic devices are included. [ABSTRACT FROM AUTHOR]

As the fourth most important cancer management strategy except surgery, chemotherapy and radiotherapy, cancer immunotherapy has been confirmed to elicit durable antitumor effects in the clinic by leveraging the patient’s own immune system to eradicate the cancer cells. However, the limited population of patients who benefit from the current immunotherapies and the immune related adverse events hinder its development. The immunosuppressive microenvironment is the main cause of the failure, which leads to cancer immune evasion and immunity cycle blockade. Encouragingly, nanotechnology has been engineered to enhance the efficacy and reduce off-target toxicity of their therapeutic cargos by spatiotemporally controlling the biodistribution and release kinetics. Among them, lipid-based nanoparticles are the first nanomedicines to make clinical translation, which are now established platforms for diverse areas. In this perspective, we discuss the available lipid-based nanoparticles in research and market here, then describe their application in cancer immunotherapy, with special emphasis on the T cells-activated and macrophages-targeted delivery system. Through perpetuating each step of cancer immunity cycle, lipid-based nanoparticles can reduce immunosuppression and promote drug delivery to trigger robust antitumor response.

With its unique properties and potential applications, nanoparticle-based delivery platforms for messenger RNA (mRNA) vaccines have gained significant attention in recent years. Nanoparticles have the advantages of enhancing immunogenicity, targeting delivery, and improving stability, providing a new solution for drug and vaccine delivery. In some clinical studies, a variety of nanoparticle delivery platforms have been gradually applied to a wide range of vaccine applications. Current research priorities are exploring various types of nanoparticles as vaccine delivery systems to enhance vaccine stability and immunogenicity. Lipid nanoparticles (LNPs) have shown promising potential in preclinical and clinical studies on the efficient delivery of antigens to immune cells. Moreover, lipid nanoparticles and other nanoparticles for nucleic acids, especially for mRNA delivery systems, have shown vast potential for vaccine development. In this review, we present various vaccine platforms with an emphasis on nanoparticles as mRNA vaccine delivery vehicles. We describe several novel nanoparticle delivery platforms for mRNA vaccines, such as lipid-, polymer-, and protein-based nanoparticles. In addition, we provide an overview of the anti-tumor immunity of nanovaccines against different tumors in cancer immunotherapy. Finally, we outline future perspectives and remaining challenges for this promising technology of nanoparticle-based delivery platforms for vaccines.

This review aims to provide a thorough examination of the benefits, challenges, and advancements in utilizing lipids for more effective drug delivery, ultimately contributing to the development of innovative approaches in pharmaceutical science. Lipophilic drugs, characterized by low aqueous solubility, present a formidable challenge in achieving effective delivery and absorption within the human body. To address this issue, one promising approach involves harnessing the potential of lipids. Lipids, in their diverse forms, serve as carriers, leveraging their unique capacity to enhance solubility, stability, and absorption of these challenging drugs. By facilitating improved intestinal solubility and selective lymphatic absorption of porously permeable drugs, lipids offer an array of possibilities for drug delivery. This versatile characteristic not only bolsters the pharmacological efficacy of drugs with low bioavailability but also contributes to enhanced therapeutic performance, ultimately reducing the required dose size and associated costs. This comprehensive review delves into the strategic formulation approaches that employ lipids as carriers to ameliorate drug solubility and bioavailability. Emphasis is placed on the critical considerations of lipid type, composition, and processing techniques when designing lipid-based formulations. This review meticulously examines the multifaceted challenges that come hand in hand with lipid-based formulations for lipophilic drugs, offering an insightful perspective on future trends. Regulatory considerations and the broad spectrum of potential applications are also thoughtfully discussed. In summary, this review presents a valuable repository of insights into the effective utilization of lipids as carriers, all aimed at elevating the bioavailability of lipophilic drugs.

Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD) are an accelerating global health problem as life expectancy rises worldwide. Despite their significant burden in public health systems to date, the existing treatments only manage the symptoms without slowing down disease progression. Thus, the ongoing neurodegenerative process remains untreated. Moreover, the stronghold of the brain—the blood–brain barrier (BBB)—prevents drug penetrance and dwindles effective treatments. In the last years, nanotechnology‐based drug delivery systems (DDS) have become a promising approach to target and treat these disorders related to the central nervous system (CNS). PLGA based nanoparticles (NPs) were the first employed DDS for effective drug delivery. However, the poor drug loading capacity and localized immunogenicity prompted the scientific community to move to another DDS such as lipid‐based NPs. Despite the lipid NPs' safety and effectiveness, their off‐target accumulation together with the denominated CARPA (complement activation‐related pseudo allergy) reaction has limited their complete clinical translation. Recently, biological NPs naturally secreted by cells, termed as extracellular vesicles (EVs) have emerged as promising more complex biocompatible DDS. In addition, EVs act as dual players in NDs treatment, as a "cell free" therapy themselves, as well as new biological NPs with numerous characteristics that qualify them as promising carriers over synthetic DDS. The present review aims to display advantages, drawbacks, current limitations and future prospective of the previously cited synthetic and biological DDS to enter the brain and treat one of 21st century most challenging diseases, NDs. This article is categorized under:Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have shown remarkable success in cancer treatment. However, in cancer patients without sufficient antitumor immunity, numerous data indicate that blocking the negative signals elicited by immune checkpoints is ineffective. Drugs that stimulate immune activation‐related pathways are emerging as another route for improving immunotherapy. In addition, the development of nanotechnology presents a promising platform for tissue and cell type‐specific delivery and improved uptake of immunomodulatory agents, ultimately leading to enhanced cancer immunotherapy and reduced side effects. In this review, we summarize and discuss the latest developments in nanoparticles (NPs) for cancer immuno‐oncology therapy with a focus on lipid‐based NPs (lipid‐NPs), including the characteristics and advantages of various types. Using the agonists targeting stimulation of the interferon genes (STING) transmembrane protein as an exemplar, we review the potential of various lipid‐NPs to augment STING agonist therapy. Furthermore, we present recent findings and underlying mechanisms on how STING pathway activation fosters antitumor immunity and regulates the tumor microenvironment and provide a summary of the distinct STING agonists in preclinical studies and clinical trials. Ultimately, we conduct a critical assessment of the obstacles and future directions in the utilization of lipid‐NPs to enhance cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Tumors of the Central nervous System (CNS) are a spectrum of neoplasms that range from benign lesions to highly malignant and aggressive lesions. Despite aggressive multimodal treatment approaches, the morbidity and mortality are high with dismal survival outcomes in these malignant tumors. Moreover, the non-specificity of conventional treatments substantiates the rationale for precise therapeutic strategies that selectively target infiltrating tumor cells within the brain, and minimize systemic and collateral damage. With the recent advancement of nanoplatforms for biomaterials applications, lipid-based nanoparticulate systems present an attractive and breakthrough impact on CNS tumor management. Lipid nanoparticles centered immunotherapeutic agents treating malignant CNS tumors could convene the clear need for precise treatment strategies. Immunotherapeutic agents can selectively induce specific immune responses by active or innate immune responses at the local site within the brain. In this review, we discuss the therapeutic applications of lipid-based nanoplatforms for CNS tumors with an emphasis on revolutionary approaches in brain targeting, imaging, and drug and gene delivery with immunotherapy. Lipid-based nanoparticle platforms represent one of the most promising colloidal carriers for chemotherapeutic, and immunotherapeutic drugs. Their current application in oncology especially in brain tumors has brought about a paradigm shift in cancer treatment by improving the antitumor activity of several agents that could be used to selectively target brain tumors. Subsequently, the lab-to-clinic transformation and challenges towards translational feasibility of lipid-based nanoplatforms for drug and gene/immunotherapy delivery in the context of CNS tumor management is addressed. [ABSTRACT FROM AUTHOR]

Moxifloxacin (MOX) is an important antibiotic commonly used in the treatment of recurrent Escherichia coli (E. coli) infections. The aim of this study was to investigate its antibacterial efficiency when used with solid lipid nanoparticles (SNLs) and nanostructured lipid carriers (NLCs) as delivery vehicles. For this purpose we designed two SLNs (SLN1 and SLN2) and two NLCs (NLC1 and NLC2) of different characteristics (particle size, size distribution, zeta potential, and encapsulation efficiency) and loaded them with MOX to determine its release, antibacterial activity against E. coli, and their cytotoxicity to the RAW 264.7 monocyte/macrophage-like cell line in vitro. With bacterial uptake of 57.29 %, SLN1 turned out to be significantly more effective than MOX given as standard solution, whereas SLN2, NLC1, and NLC2 formulations with respective bacterial uptakes of 50.74 %, 39.26 %, and 32.79 %, showed similar activity to standard MOX. Cytotoxicity testing did not reveal significant toxicity of nanoparticles, whether MOX-free or MOX-loaded, against RAW 264.7 cells. Our findings may show the way for a development of effective lipid carriers that reduce side effects and increase antibacterial treatment efficacy in view of the growing antibiotic resistance.

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Simple Summary: Lipid-based nanocarriers have proved effective for drug and hormone delivery. The androgen hormone 17 alpha-methyltestosterone (MT) is used for sex reversal in tilapia; however, the hormone has biopharmaceutical limitations such as insolubility, low stability, limited intestinal absorption, and poor bioavailability. Incorporating MT into lipid-based nanocarriers to improve hormone uptake in tilapia is an interesting prospect. In the present study, we reported an improved version of alkyl polyglucosides loaded with 17 alpha-methyltestosterone integrated into nanostructured lipid carriers (APG-NLC) for the masculinization of red tilapia (Oreochromis spp.) via oral administration as a feed additive. We demonstrated that nanotechnology-based drug delivery systems represent a novel and promising strategy for improving the oral absorption of these androgen hormones, resulting in a 50% w/w reduction in the hormonal dosage during the sex reversal period. Therefore, we strongly believe that this newly optimized nanotechnology is one of the solutions for sustainable aquaculture production. The aim of the present study was to optimize a masculinization platform for the production of all-male red tilapia fry by oral administration of 30 and 60 ppm of MT and alkyl polyglucoside nanostructured lipid carriers (APG-NLC) loaded with MT, respectively, for 14 and 21 days. The characterization, encapsulation efficiency and release kinetics of MT in lipid-based nanoparticles were assessed in vitro. The results showed that the MT-loaded nanoparticles were spherical, ranging from 80 to 125 nm in size, and had a negative charge with a narrow particle distribution. The APG-NLC loaded with MT provided higher physical stability and encapsulation efficacy than the NLC. The release rate constants of MT from MT-NLC and MT-APG-NLC were higher than those of free MT, which is insoluble in aqueous media. There was no significant difference in survival between the fish administered MT or the those fed orally with MT-APG-NLC fish. According to the logistic regression analysis, the sex reversal efficacy of MT-APG-NLC (30 ppm) and MT (60 ppm), resulted in significantly higher numbers of males after 21 days of treatment compared with the controls. The production cost of MT-APG-NLC (30 ppm) after 21 days of treatment was reduced by 32.9% compared with the conventional MT treatment group (60 ppm). In all the treatments, the length–weight relationship (LWR) showed negatively allomeric growth behavior (b < 3), with a relative condition factor (Kn) of more than 1. Therefore, MT-APG-NLC (30 ppm) would seem to be a promising, cost-effective way to reduce the dose of MT used for the masculinization of farmed red tilapia. [ABSTRACT FROM AUTHOR]

Lipid-based nanoparticles (LBNPs) are an important tool for the delivery of a diverse set of drug cargoes, including small molecules, oligonucleotides, and proteins and peptides. Despite their development over the past several decades, this technology is still hindered by issues with the manufacturing processes leading to high polydispersity, batch-to-batch and operator-dependent variability, and limits to the production volumes. To overcome these issues, the use of microfluidic techniques in the production of LBNPs has sharply increased over the past two years. Microfluidics overcomes many of the pitfalls seen with conventional production methods, leading to reproducible LBNPs at lower costs and higher yields. In this review, the use of microfluidics in the preparation of various types of LBNPs, including liposomes, lipid nanoparticles, and solid lipid nanoparticles for the delivery of small molecules, oligonucleotides, and peptide/protein drugs is summarized. Various microfluidic parameters, as well as their effects on the physicochemical properties of LBNPs, are also discussed. [ABSTRACT FROM AUTHOR]

Gemcitabine (GEM) is a chemotherapeutic drug widely used for treating pancreatic cancer and other cancers. Despite its efficacy, GEM is associated with adverse side effects and tumor resistance, hampering its therapeutic outcomes. To address these challenges, innovative strategies have emerged to enhance GEM delivery. This comprehensive review explores various distribution systems, including polymer-based platforms, liposomes, and inorganic nanoparticles, highlighting their unique characteristics for improving GEM efficacy in cancer treatment. Additionally, we discuss the promising approach of codelivery with genes and present several methods for augmenting GEM's chemotherapeutic properties. Our findings shed light on novel insights and provide recommendations for overcoming the limitations associated with GEM, guiding researchers and clinicians toward more effective cancer therapies.

Abstract Immune checkpoint inhibitors (ICIs) have shown remarkable success in cancer treatment. However, in cancer patients without sufficient antitumor immunity, numerous data indicate that blocking the negative signals elicited by immune checkpoints is ineffective. Drugs that stimulate immune activation‐related pathways are emerging as another route for improving immunotherapy. In addition, the development of nanotechnology presents a promising platform for tissue and cell type‐specific delivery and improved uptake of immunomodulatory agents, ultimately leading to enhanced cancer immunotherapy and reduced side effects. In this review, we summarize and discuss the latest developments in nanoparticles (NPs) for cancer immuno‐oncology therapy with a focus on lipid‐based NPs (lipid‐NPs), including the characteristics and advantages of various types. Using the agonists targeting stimulation of the interferon genes (STING) transmembrane protein as an exemplar, we review the potential of various lipid‐NPs to augment STING agonist therapy. Furthermore, we present recent findings and underlying mechanisms on how STING pathway activation fosters antitumor immunity and regulates the tumor microenvironment and provide a summary of the distinct STING agonists in preclinical studies and clinical trials. Ultimately, we conduct a critical assessment of the obstacles and future directions in the utilization of lipid‐NPs to enhance cancer immunotherapy.

Tumors of the Central nervous System (CNS) are a spectrum of neoplasms that range from benign lesions to highly malignant and aggressive lesions. Despite aggressive multimodal treatment approaches, the morbidity and mortality are high with dismal survival outcomes in these malignant tumors. Moreover, the non-specificity of conventional treatments substantiates the rationale for precise therapeutic strategies that selectively target infiltrating tumor cells within the brain, and minimize systemic and collateral damage. With the recent advancement of nanoplatforms for biomaterials applications, lipid-based nanoparticulate systems present an attractive and breakthrough impact on CNS tumor management. Lipid nanoparticles centered immunotherapeutic agents treating malignant CNS tumors could convene the clear need for precise treatment strategies. Immunotherapeutic agents can selectively induce specific immune responses by active or innate immune responses at the local site within the brain. In this review, we discuss the therapeutic applications of lipid-based nanoplatforms for CNS tumors with an emphasis on revolutionary approaches in brain targeting, imaging, and drug and gene delivery with immunotherapy. Lipid-based nanoparticle platforms represent one of the most promising colloidal carriers for chemotherapeutic, and immunotherapeutic drugs. Their current application in oncology especially in brain tumors has brought about a paradigm shift in cancer treatment by improving the antitumor activity of several agents that could be used to selectively target brain tumors. Subsequently, the lab-to-clinic transformation and challenges towards translational feasibility of lipid-based nanoplatforms for drug and gene/immunotherapy delivery in the context of CNS tumor management is addressed.

In recent years, due to their distinctive and adaptable therapeutic effects, many natural bioactive compounds have been commonly used to treat diseases. Their limited solubility, low bioavailability, inadequate gastrointestinal tract stability, high metabolic rate, and shorter duration of action limited their pharmaceutical applications. However, those can be improved using nanotechnology to create various drug delivery systems, including lipid-based nanoparticles, to adjust the compounds’ physicochemical properties and pharmacokinetic profile. Because of the enormous technical advancements made in the fundamental sciences and the physical and chemical manipulation of individual atoms and molecules, the subject of nanotechnology has experienced revolutionary growth. By fabricating certain functionalized particles, nanotechnology opens an innovative horizon in research and development for overcoming restrictions, including traditional medication administration systems. Nanotechnology-driven bioactive compounds are certain to have a high impact and clinical value for current and future uses. Lipid-based nanotechnologies were shown to deliver a range of naturally occurring bioactive compounds with decent entrapment potential and stability, a successfully controlled release, increased bioavailability, and intriguing therapeutic activity. This review outlines bioactive compounds such as paclitaxel, curcumin, rhodomyrtone, quercetin, kaempferol, resveratrol, epigallocatechin-3-gallate, silymarin, and oridonin, fortified within either a natural or synthetic lipid-based drug delivery system based on nanotechnology and their evaluation and clinical considerations.

Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, affect a wide variety of the population and pose significant challenges with progressive and irreversible neural cell loss. The limitations of brain-targeting therapies and the unclear molecular mechanisms driving neurodegeneration hamper the possibility of developing successful treatment options. Thus, nanoscale drug delivery platforms offer a promising solution. This paper explores and compares lipidic nanoparticles, extracellular vesicles (EVs), and hybrid liposomal–EV nanoplatforms as advanced approaches for targeted delivery to combat neurodegeneration. Lipidic nanoparticles are well-characterized platforms that allow multi-drug loading and scalable production. Conversely, EVs offer the ability of selectively targeting specific tissues and high biocompatibility. The combination of these two platforms in one could lead to promising results in the treatment of neurodegeneration. However, many issues, such as the regulatory framework, remain to be solved before these novel products are translated into clinical practice.

CRISPR/Cas mediated gene-editing has opened new avenues for therapies that show great potential for treating or curing cancers, genetic disorders, and microbial infections such as HIV. CRISPR/Cas9 tool is highly efficacious in revolutionizing the advent of genome editing; however, its efficient and safe delivery is a major hurdle due to its cellular impermeability and instability. Nano vectors could be explored to scale up the safe and effective delivery of CRISPR/Cas9. This review highlights the importance of CRISPR/Cas9 genome editing system in cancer treatment along with the effect of lipid-based nanoparticles in its safe delivery to cancer cells. The solid-lipid nanoparticles, nanostructured lipid carrier, lipid nanoparticles and niosomes have shown great effect in the delivery of CRISPR compounds to the cancer cells. The design and genome editing application in cancer therapy has been discussed along with the future concern and prospects of lipid nanoparticle based CRISPR/Cas9 has been focused toward the end. [ABSTRACT FROM AUTHOR]

Hypertension is a major health concern globally. Elevated blood pressure, initiated and maintained by the brain, is defined as neurogenic hypertension (NH), which accounts for nearly half of all hypertension cases. A significant increase in angiotensin II-mediated sympathetic nervous system activity within the brain is known to be the key driving force behind NH. Blood pressure control in NH has been demonstrated through intracerebrovascular injection of agents that reduce the sympathetic influence on cardiac functions. However, traditional antihypertensive agents lack effective brain permeation, making NH management extremely challenging. Therefore, developing strategies that allow brain-targeted delivery of antihypertensives at the therapeutic level is crucial. Targeting nanotherapeutics have become popular in delivering therapeutics to hard-to-reach regions of the body, including the brain. Despite the frequent use of nanotherapeutics in other pathological conditions such as cancer, their use in hypertension has received very little attention. This review discusses the underlying pathophysiology and current management strategies for NH, as well as the potential role of targeted therapeutics in improving current treatment strategies. [ABSTRACT FROM AUTHOR]

Calendula genus is a group of herbs used in the treatment of some human diseases and disorders, such as wounds, inflammations, and cancers. Calendula was used as medicine from humans' earliest ages to the present days; from using the plant itself as herbal tea in the renaissance to using the calendulas as tablets and other drug formations. However, these herbal treatments have some disadvantages, including unwanted side effects in some organs of the body, toxicities, and fast-ending therapeutic effects. Therefore, researchers have made special attention to overcome these disadvantages via drug delivery formulations and using recent drug delivery systems such as nanotubes, liposomes, carrier polymers, lipid-based nanoparticles (NPs) (e.g., nanostructured lipid carriers (NLCs) or solid lipid nanoparticles (SLNs)), fullerenes and so forth. These carriers and delivery systems could help improve the marigold extract (ME) and oil efficacy, leading to a decrease in toxicity and other side effects. Carriers loaded with ME can be an effective formulation design in the treatment of many diseases in humans such as cancer especially if a suitable carrier is chosen in the formulation step like NLCs or metal nanocarriers. The aim of this paper is to provide an extensive review of various drug delivery technologies on Calendula and show how effective it is in improving therapeutic effect by reviewing some of the newest and best research articles and presenting their data in summary form. Calendula is a group of plants that is used in the treatment of a wide range of diseases like cancers. Various methods are used in modern drug delivery, such as carriers, polymers, and nano-robots, which will increase the effectiveness and reduce the side effects of the treatment process. [ABSTRACT FROM AUTHOR]

In the pharmaceutical industry, liposomes and polymeric nanoparticles are the two most commonly studied delivery vehicles. A new technique uses lipid-polymeric hybrid nanoparticles (LPHNPs) with a polymeric core, and a shell made up of lipid-lipid-PEG lipids. They have properties which complement polymer nanoparticles and liposomes, and they have the potential to improve the physical stability and biocompatibility of the active pharmaceutical ingredient encapsulated in them. Evaporating the solvent from a dual-phase solution containing lipid and polymer is one of the most effective methods for producing lipid polymeric hybrid nanoparticles. The LPHNPs applications have also been significantly expanded to include combinational and active targeted drug delivery, as well as delivery of genetic materials, vaccines, and diagnostic imaging agents, in addition to single drug delivery for anticancer therapy, like Glioblastoma. The main agenda of this compilation was to address the effects of LPHNPs on Glioblastoma treatment. This compilation also highlights some of the formulation techniques and issues that arise during the preparation of LPHNPs. This review also discusses recent developments in core-shell lipid-polymer hybrid nanoparticles, which were conferred in considerable detail later in this article. The main issue which arises while using nanoparticles with polymer is entrapment efficiency. Because of their hybrid components, LPHNPs have proven to solve this problem to a large extent. The recent research trends suggest that lipid polymeric hybrid nanoparticles will prove to be highly effective or productive in treating diseases such as Glioblastoma.

A variety of strategies for producing high-quality nanoparticles have been reported in recent years. Batch-based bottom-up and top-down technologies are generally the most efficient methods, but present a number of challenges, particularly in terms of variability, safety, sustainability and large-scale production. In this study, a scalable, semi-continuous production line was built by connecting individual processing units, including a high shear mixing device, the Microfluidizer® technology and a cooling system. Each unit was equipped with an adequate temperature control to allow solvent-free production of solid lipid nanoparticles (consisting of Precirol® ATO 5 or Gelucire® 43/01) and nanostructured lipid carriers (additionally comprising Labrafac™ lipophile WL 1349). Subsequently, critical formulation parameters and critical process parameters (CPPs) of the individual processing units and their effects on particle size (i.e., critical quality attribute (CQA)) were investigated to identify appropriate input parameters for the subsequent Design of Experiment (DoE) studies conducted after linking the process units to a semi-continuous production line. For particle size monitoring, spatially resolved dynamic light scattering (SR-DLS) measurements were conducted and compared to standard DLS measurements to evaluate the applicability of SR-DLS as an inline monitoring tool. It was found that matrix composition, emulsifier concentration, pressure and number of cycles when processing through Microfluidizer® processor were the most influencing parameters. By optimizing these parameters, five-times higher throughputs could be achieved by the semi-continuous manufacturing line. In addition, the particle size measurements with SR-DLS confirmed the feasibility of implementing this technology for real-time particle size monitoring as an important safety factor in quality control. [Display omitted] [ABSTRACT FROM AUTHOR]

• SEC method for separation of liposomes and lipodisks. • Nanoparticle shape heterogeneity analysis by scaling law of R g vs. MW. • A semi-quantitative model to predict nanoparticle morphology. Nanoparticle-based drug delivery systems are rising technologies to access challenging therapeutic targets. Following commercial success of lipid-based nanoparticles (LBNP), accruing understandings of nanoparticle structures and critical quality attributes through advanced analytics are beneficial to future clinical development and generalization of this delivery platform. The morphological attributes of nanoparticles, such as shape, can affect uptake, cell-interaction, drug release, circulation, and flow. Gaining an understanding of these structure-activity relationships in early-stage formulation development is important because mix morphologies can affect quality and potency but often exist before process control strategies are fully implemented. In this study, we used shape heterogeneous nanoparticle mixtures, containing various populations of liposomes and lipodisks, as a model system and developed an online semi-quantitative method to characterize the nanoparticle shape heterogeneity by size exclusion chromatography (SEC) coupled with multi-angle light scattering (MALS). The liposomes and lipodisks were separated in SEC when their sizes were ∼3 fold different. When the particles of different shapes were in similar sizes, size-based separation was not always feasible. Instead, light scattering data distinguished liposomes and lipodisks by the scaling law linking radius of gyration and molecular weight of the nanoparticles, enabling morphological identification. A semi-quantitative model was built based on the exponential correlation between the scaling law exponents and the ratios of liposomes and lipodisks. The model was applied to test 6 random formulations made with different compositions and manufacturing processes, and the predicted liposome percentage for 5 formulations was within 25 % absolute difference from the percentage determined by cryogenic electron microscopy (cryo-EM). We envision this method being routinely used to characterize liposome and lipodisk shape heterogeneity during formulation screening as well as on stability studies. Potentially, the method can be converted to in-process control method and extended to other categories of nanoparticles beyond liposomes. [ABSTRACT FROM AUTHOR]

Infectious diseases are a predominant problem in human health. While the incidence of many pathogenic infections is controlled by vaccines, some pathogens still pose a challenging task for vaccine researchers. In order to face these challenges, the field of vaccine development has changed tremendously over the last few years. For non-replicating recombinant antigens, novel vaccine delivery systems that attempt to increase the immunogenicity by mimicking structural properties of pathogens are already approved for clinical applications. Lipid-based nanoparticles (LbNPs) of different natures are vesicles made of lipid layers with aqueous cavities, which may carry antigens and other biomolecules either displayed on the surface or encapsulated in the cavity. However, the efficacy profile of recombinant LbNP vaccines is not as high as that of live-attenuated ones. This review gives a compendious picture of two approaches that affect the immunogenicity of recombinant LbNP vaccines: (i) the incorporation of immunostimulatory agents and (ii) the utilization of pre-existing or promiscuous cellular immunity, which might be beneficial for the development of tailored prophylactic and therapeutic LbNP vaccine candidates.

In this work, lipid-based nanoparticles (LBNP) were designed to combine tyrosine kinase inhibitor (TKI) Lapatinib (LAPA) with siRNA directed against apoptosis inhibitor protein Survivin (siSurvivin) in an injectable form. This nanosystem is based on lipid nanocapsules (LNCs) coated with a cationic polymeric shell composed of chitosan grafted through a transacylation reaction. The hydrophobic LAPA is solubilized in the inner oily core, while hydrophilic siRNA is associated electrostatically onto the nanocarrier's surface. The co-loaded LBNP showed a narrow size distribution (polydispersity index (PDI) < 0.3), a size of 130 nm, and a slightly positive zeta potential (+21 mV). LAPA and siRNA were loaded in LBNP at a high rate of >90% (10.6 mM) and 100% (4.6 µM), respectively. The siRNA-LAPA_LBNP was readily uptaken by the human epidermal growth factor receptor 2 overexpressed (HER2+) breast cancer cell line SK-BR-3. Moreover, the cytotoxicity studies confirmed that the blank chitosan decorated LBNP is not toxic to the cells with the tested concentrations, which correspond to LAPA concentrations from 1 to 10 µM, at different incubation times up to 96 h. Furthermore, siCtrl.-LAPA_LBNP had a more cytotoxic effect than Lapatinib salt, while siSurvivin-LAPA_LBNP had a significant synergistic cytotoxic effect compared to siCtrl.-LAPA_LBNP. All these findings suggested that the developed modified LBNP could potentiate anti-Survivin siRNA and LAPA anti-cancer activity. [ABSTRACT FROM AUTHOR]