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Lipid-based nanocarriers have emerged as helpful tools to deliver sensible biomolecules such as proteins and oligonucleotides. To have a fast and robust microfluidic-based nanoparticle synthesis method, the setup of versatile equipment should allow for the rapid transfer to scale cost-effectively while ensuring tunable, precise and reproducible nanoparticle attributes. The present work aims to assess the effect of different micromixer geometries on the manufacturing of lipid nanocarriers taking into account the influence on the mixing efficiency by changing the fluid–fluid interface and indeed the mass transfer. Since the geometry of the adopted micromixer varies from those already published, a Design of Experiment (DoE) was necessary to identify the operating (total flow, flow rate ratio) and formulation (lipid concentration, lipid molar ratios) parameters affecting the nanocarrier quality. The suitable application of the platform was investigated by producing neutral, stealth and cationic liposomes, using DaunoXome®, Myocet®, Onivyde® and Onpattro® as the benchmark. The effect of condensing lipid (DOTAP, 3–10–20 mol%), coating lipids (DSPE-PEG550 and DSPE-PEG2000), as well as structural lipids (DSPC, eggPC) was pointed out. A very satisfactory encapsulation efficiency, always higher than 70%, was successfully obtained for model biomolecules (myoglobin, short and long nucleic acids). [ABSTRACT FROM AUTHOR]

Lipid nanoparticles (LNP) have gained much attention after the approval of mRNA COVID-19 vaccines. The considerable number of currently ongoing clinical studies are testament to this fact. These efforts towards the development of LNPs warrant an insight into the fundamental developmental aspects of such systems. In this review, we discuss the key design aspects that confer efficacy to a LNP delivery system, i.e., potency, biodegradability, and immunogenicity. We also cover the underlying considerations regarding the route of administration and targeting of LNPs to hepatic and non-hepatic targets. Furthermore, since LNP efficacy is also a function of drug/nucleic acid release within endosomes, we take a holistic view of charged-based targeting approaches of LNPs not only in the context of endosomal escape but also in relation to other comparable target cell internalization strategies. Electrostatic charge-based interactions have been used in the past as a potential strategy to enhance the drug release from pH-sensitive liposomes. In this review, we cover such strategies around endosomal escape and cell internalization in low pH tumor micro-environments. [ABSTRACT FROM AUTHOR]

Nanotechnology takes the lead in providing new therapeutic options for cancer patients. In the last decades, lipid-based nanoparticles—solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), liposomes, and lipid–polymer hybrid nanoparticles—have received particular interest in anticancer drug delivery to solid tumors. To improve selectivity for target cells and, thus, therapeutic efficacy, lipid nanoparticles have been functionalized with antibodies that bind to receptors overexpressed in angiogenic endothelial cells or cancer cells. Most papers dealing with the preclinical results of antibody-conjugated nanoparticles claim low systemic toxicity and effective tumor inhibition, which have not been successfully translated into clinical use yet. This review aims to summarize the current "state-of-the-art" in anticancer drug delivery using antibody-functionalized lipid-based nanoparticles. It includes an update on promising candidates that entered clinical trials and some explanations for low translation success. [ABSTRACT FROM AUTHOR]

Due to complicated anatomical and physical properties, targeted drug delivery to ocular tissues continues to be a key challenge for formulation scientists. Various attempts are currently being made to improve the in vivo performance of therapeutic molecules by encapsulating them in various nanocarrier systems or devices and administering them via invasive/non-invasive or minimally invasive drug administration methods. Biocompatible and biodegradable lipid nanoparticles have emerged as a potential alternative to conventional ocular drug delivery systems to overcome various ocular barriers. Lipid-based nanocarrier systems led to major technological advancements and therapeutic advantages during the last few decades of ocular therapy, such as high precorneal residence time, sustained drug release profile, minimum dosing frequency, decreased drug toxicity, targeted site delivery, and, therefore, an improvement in ocular bioavailability. In addition, such formulations can be given as fine dispersion in patient-friendly droppable preparation without causing blurred vision and ocular sensitivity reactions. The unique advantages of lipid nanoparticles, namely, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, and liposomes in intraocular targeted administration of various therapeutic drugs are extensively discussed. Ongoing and completed clinical trials of various liposome-based formulations and various characterization techniques designed for nanoemulsion in ocular delivery are tabulated. This review also describes diverse solid lipid nanoparticle preparation methods, procedures, advantages, and limitations. Functionalization approaches to overcome the drawbacks of lipid nanoparticles, as well as the exploration of new functional additives with the potential to improve the penetration of macromolecular pharmaceuticals, would quickly progress the challenging field of ocular drug delivery systems. [ABSTRACT FROM AUTHOR]