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Many pharmaceutically active molecules are highly lipophilic, which renders their administration and adsorption in patients extremely challenging. Among the countless strategies to overcome this problem, synthetic nanocarriers have demonstrated superb efficiency as drug delivery systems, since encapsulation can effectively prevent a molecules' degradation, thus ensuring increased biodistribution. However, metallic and polymeric nanoparticles have been frequently associated with possible cytotoxic side effects. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), which are prepared with physiologically inert lipids, therefore emerged as an ideal strategy to bypass toxicities issues and avoid the use of organic solvents in their formulations. Different approaches to preparation, using only moderate amounts of external energy to facilitate a homogeneous formation, have been proposed. Greener synthesis strategies have the potential to provide faster reactions, more efficient nucleation, better particle size distribution, lower polydispersities, and furnish products with higher solubility. Particularly microwave-assisted synthesis (MAS) and ultrasound-assisted synthesis (UAS) have been utilized in the manufacturing of nanocarrier systems. This narrative review addresses the chemical aspects of those synthesis strategies and their positive influence on the characteristics of SLNs and NLCs. Furthermore, we discuss the limitations and future challenges for the manufacturing processes of both types of nanoparticles. [ABSTRACT FROM AUTHOR]

The major risk factor associated with the development of gastric cancer is chronic infection with Helicobacter pylori. The available treatments, based on a cocktail of antibiotics, fail in up to 40% of patients and disrupt their gut microbiota. The potential of blank nanostructured lipid carriers (NLC) for H. pylori eradication was previously demonstrated by us. However, the effect of NLC charge, size and protein corona on H. pylori-specific bactericidal activity herein studied was unknown at that time. All developed NLC formulations proved bactericidal against H. pylori. Although cationic NLC had 10-fold higher bactericidal activity than anionic NLC, they lacked specificity, since Lactobacillus acidophilus was also affected. Anionic NLC achieved complete clearance in both H. pylori morphologies (rod- and coccoid-shape) by inducing alterations in bacteria membranes and the cytoplasm, as visualized by transmission electron microscopy (TEM). The presence of an NLC protein corona, composed of 93% albumin, was confirmed by mass spectrometry. This protein corona delayed the bactericidal activity of anionic NLC against H. pylori and hindered NLC activity against Escherichia coli. Overall, these results sustain the use of NLC as a promising antibiotic-free strategy targeting H. pylori. [ABSTRACT FROM AUTHOR]

According to the WHO, cancer caused almost 10 million deaths worldwide in 2020, i.e., almost one in six deaths. Among the most common are breast, lung, colon and rectal and prostate cancers. Although the diagnosis is more perfect and spectrum of available drugs is large, there is a clear trend of an increase in cancer that ends fatally. A major advance in treatment was the introduction of gentler antineoplastics for targeted therapy–tyrosine kinase inhibitors (TKIs). Although they have undoubtedly revolutionized oncology and hematology, they have significant side effects and limited efficacy. In addition to the design of new TKIs with improved pharmacokinetic and safety profiles, and being more resistant to the development of drug resistance, high expectations are placed on the reformulation of TKIs into various drug delivery lipid-based nanosystems. This review provides an insight into the history of chemotherapy, a brief overview of the development of TKIs for the treatment of cancer and their mechanism of action and summarizes the results of the applications of self-nanoemulsifying drug delivery systems, nanoemulsions, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles and nanostructured lipid carriers used as drug delivery systems of TKIs obtained in vitro and in vivo. [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]

Ursolic acid, a triterpene produced by plants, displayed leishmanicidal activity in vitro and in vivo; however, the low solubility of this triterpene limits its efficacy. To increase the activity of ursolic acid (UA), this triterpene was entrapped in nanostructured lipid carriers (UA-NLC), physical-chemical parameters were estimated, the toxicity was assayed in healthy golden hamsters, and the efficacy of UA-NLC was studied in experimental visceral leishmanisis. UA-NLC exhibited a spherical shape with a smooth surface with a size of 266 nm. UA-NLC displayed low polydispersity (PDI = 0.18) and good colloidal stability (−29.26 mV). Hamsters treated with UA-NLC did not present morphological changes in visceral organs, and the levels of AST, ALT, urea and creatinine were normal. Animals infected with Leishmania (Leishmania) infantum and treated with UA-NLC showed lower parasitism than the infected controls, animals treated with UA or Amphotericin B (AmB). The therapeutic activity of UA-NLC was associated with the increase in a protective immune response, and it was associated with a high degree of spleen and liver preservation, and the normalization of hepatic and renal functions. These data indicate that the use of lipid nanoparticles as UA carriers can be an interesting strategy for the treatment of leishmaniasis. [ABSTRACT FROM AUTHOR]

Nano-sized drug transporters have become an efficient approach with considerable commercial values. Nanomedicine is not only limited to drug delivery by means of different administration routes, such as intravenous, oral, transdermal, nasal, pulmonary, and more, but also has applications in a multitude of areas, such as a vaccine, antibacterial, diagnostics and imaging, and gene delivery. This review will focus on lipid nanosystems with a wide range of applications, taking into consideration their composition, properties, and physical parameters. However, designing suitable protocol for the physical evaluation of nanoparticles is still conflicting. The main obstacle is concerning the sensitivity, reproducibility, and reliability of the adopted methodology. Some important techniques are compared and discussed in this report. Particularly, a comparison between different techniques involved in (a) the morphologic characterization, such as Cryo-TEM, SEM, and X-ray; (b) the size measurement, such as dynamic light scattering, sedimentation field flow fractionation, and optical microscopy; and (c) surface properties, namely zeta potential measurement, is described. In addition, an amperometric tool in order to investigate antioxidant activity and the response of nanomaterials towards the skin membrane has been presented. [ABSTRACT FROM AUTHOR]

The aim of this study was the optimization of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in terms of physicochemical and biopharmaceutical properties, to develop effective and stable aqueous liquid formulations of hydrochlorothiazide, suitable for paediatric therapy, overcoming its low-solubility and poor-stability problems. Based on solubility studies, Precirol® ATO5 and Transcutol® HP were used as solid and liquid lipids, respectively. The effect of different surfactants, also in different combinations and at different amounts, on particle size, homogeneity and surface-charge of nanoparticles was carefully investigated. The best formulations were selected for drug loading, and evaluated also for entrapment efficiency and release behaviour. For both SLN and NLC series, the use of Gelucire® 44/14 as surfactant rather than PluronicF68 or Tween® 80 yielded a marked particle size reduction (95–75 nm compared to around 600–400 nm), and an improvement in entrapment efficiency and drug release rate. NLC showed a better performance than SLN, reaching about 90% entrapped drug (vs. 80%) and more than 90% drug released after 300 min (vs. about 65%). All selected formulations showed good physical stability during 6-month storage at 4 °C, but a higher loss of encapsulated drug was found for SLNs (15%) than for NLCs (<5%). Moreover, all selected formulations revealed the absence of any cytotoxic effect, as assessed by a cell-viability test on Caco-2 cells and are able to pass the intestinal epithelium as suggested by Caco-2 uptake experiments. [ABSTRACT FROM AUTHOR]

Atazanavir (ATZ) presents poor brain availability when administered orally, which poses a major hurdle in its use as an effective therapy for the management of NeuroAIDS. The utilization of nanostructured lipid carriers (NLCs) in conjunction with the premeditated use of excipients can be a potential approach for overcoming the limited ATZ brain delivery. Methods: ATZ-loaded NLC was formulated using the quality by design-enabled approach and further optimized by employing the Box–Behnken design. The optimized nanoformulation was then characterized for several in vitro and in vivo assessments. Results: The optimized NLC showed small particle size of 227.6 ± 5.4 nm, high entrapment efficiency (71.09% ± 5.84%) and high drug loading capacity (8.12% ± 2.7%). The release pattern was observed to be biphasic exhibiting fast release (60%) during the initial 2 h, then trailed by the sustained release. ATZ-NLC demonstrated a 2.36-fold increase in the cumulative drug permeated across the rat intestine as compared to suspension. Pharmacokinetic studies revealed 2.75-folds greater Cmax in the brain and 4-fold improvement in brain bioavailability signifying the superiority of NLC formulation over drug suspension. Conclusion: Thus, NLC could be a promising avenue for encapsulating hydrophobic drugs and delivering it to their target site. The results suggested that increase in bioavailability and brain-targeted delivery by NLC, in all plausibility, help in improving the therapeutic prospects of atazanavir. [ABSTRACT FROM AUTHOR]