Editorial: Anti-cancer drug delivery: lipid-based nanoparticles

Cancer continues to pose significant challenges that require extensive attention and efforts from the scientific community. The battle against cancer encompasses the development of effective and safe therapeutic approaches. However, achieving this balance is highly complex for anticancer therapies, as they often exhibit intense intrinsic cytotoxicity, affecting both cancerous and healthy cells and resulting in substantial toxicity that limits their clinical utility. A promising strategy to address this challenge involves the selective guidance of therapeutic agents to the cancer site, minimizing off-target effects. Nanotechnology offers powerful tools to engineer smart and targeted therapeutics that preferentially accumulate in cancerous tissues . This preferential localization is achieved through the Enhanced Permeation and Retention (EPR) effect, first reported by Prof. Hiroshi Maeda in 1984 . The EPR effect leverages the leaky vasculature in tumor regions, enabling enhanced infiltration of nanotherapeutics and localizing their therapeutic effects, which is commonly described as "passive targeting ". On the other hand, nanotechnologists may also employ "active targeting" by modifying nanoparticle surfaces with homing ligands that selectively recognize cancer cells . Both passive and active targeting strategies are keys for success of nanoparticle-based drug delivery systems, and serve as a justification for the development of nanotherapeutics. Extensive literature exists on various types of nanoparticles and nanomaterials with potential applications as drug delivery systems.The authors would like to thank to the journal (Frontiers in Oncology) for providing us this opportunity to organize the research topic on "Anti-Cancer Drug Delivery: Lipid-Based Nanoparticles". We thank all the authors who contributed in this topic collection. We are also, very grateful to all the reviewers who participated in the whole manuscript review process.Scopu

Quality by Design Approach in Liposomal Formulations: Robust Product Development

Nanomedicine is an emerging field with continuous growth and differentiation. Liposomal formulations are a major platform in nanomedicine, with more than fifteen FDA-approved liposomal products in the market. However, as is the case for other types of nanoparticle-based delivery systems, liposomal formulations and manufacturing is intrinsically complex and associated with a set of dependent and independent variables, rendering experiential optimization a tedious process in general. Quality by design (QbD) is a powerful approach that can be applied in such complex systems to facilitate product development and ensure reproducible manufacturing processes, which are an essential pre-requisite for efficient and safe therapeutics. Input variables (related to materials, processes and experiment design) and the quality attributes for the final liposomal product should follow a systematic and planned experimental design to identify critical variables and optimal formulations/processes, where these elements are subjected to risk assessment. This review discusses the current practices that employ QbD in developing liposomal-based nano-pharmaceuticals

PLGA-Gold Nanocomposite: Preparation and Biomedical Applications

A composite system consisting of both organic and inorganic nanoparticles is an approach to prepare a new material exhibiting “the best of both worlds”. In this review, we highlight the recent advances in the preparation and applications of poly(lactic-co-glycolic acid)-gold nanoparticles (PLGA-GNP). With its current clinically use, PLGA-based nanocarriers have promising pharmaceutical applications and can “extract and utilize” the fascinating optical and photothermal properties of encapsulated GNP. The resulting “golden polymeric nanocarrier” can be tracked, analyzed, and visualized using the encapsulated gold nanoprobes which facilitate a better understanding of the hosting nanocarrier’s pharmacokinetics and biological fate. In addition, the “golden polymeric nanocarrier” can reveal superior nanotherapeutics that combine both the photothermal effect of the encapsulated gold nanoparticles and co-loaded chemotherapeutics. To help stimulate more research on the development of nanomaterials with hybrid and exceptional properties, functionalities, and applications, this review provides recent examples with a focus on the available chemistries and the rationale behind encapsulating GNP into PLGA nanocarriers that has the potential to be translated into innovative, clinically applicable nanomedicine.A.M.A. acknowledge funding support from the University of Jordan. The APC was funded by the University of Illinois at Urbana-Champaign

Pharmaco-toxicological effects of the novel tryptamine hallucinogen 5-MeO-MiPT on motor, sensorimotor, physiological, and cardiorespiratory parameters in mice—from a human poisoning case to the preclinical evidence

Rationale: The 5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT, known online as “Moxy”) is a new psychedelic tryptamine first identified on Italian national territory in 2014. Its hallucinogen effects are broadly well-known; however, only few information is available regarding its pharmaco-toxicological effects. Objectives: Following the seizure of this new psychoactive substances by the Arm of Carabinieri and the occurrence of a human intoxication case, in the current study we had the aim to characterize the in vivo acute effects of systemic administration of 5-MeO-MiPT (0.01–30 mg/kg i.p.) on sensorimotor (visual, acoustic, and overall tactile) responses, thermoregulation, and stimulated motor activity (drag and accelerod test) in CD-1 male mice. We also evaluated variation on sensory gating (PPI, prepulse inhibition; 0.01–10 mg/kg i.p.) and on cardiorespiratory parameters (MouseOx and BP-2000; 30 mg/kg i.p.). Lastly, we investigated the in silico ADMET (absorption, distribution, metabolism, excretion, toxicity) profile of 5-MeO-MiPT compared to 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) and N,N-dimethyltryptamine (DMT). Results: This study demonstrates that 5-MeO-MiPT dose-dependently inhibits sensorimotor and PPI responses and, at high doses, induces impairment of the stimulated motor activity and cardiorespiratory changes in mice. In silico prediction shows that the 5-MeO-MiPT toxicokinetic profile shares similarities with 5-MeO-DIPT and DMT and highlights a cytochrome risk associated with this compound. Conclusions: Consumption of 5-MeO-MiPT can affect the ability to perform activities and pose a risk to human health status, as the correspondence between the effects induced in mice and the symptoms occurred in the intoxication case suggests. However, our findings suggest that 5-MeO-MiPT should not be excluded from research in the psychiatric therapy field

Toxicity and cellular uptake of gold nanoparticles: what we have learned so far?

Gold nanoparticles have attracted enormous scientific and technological interest due to their ease of synthesis, chemical stability, and unique optical properties. Proof-of-concept studies demonstrate their biomedical applications in chemical sensing, biological imaging, drug delivery, and cancer treatment. Knowledge about their potential toxicity and health impact is essential before these nanomaterials can be used in real clinical settings. Furthermore, the underlying interactions of these nanomaterials with physiological fluids is a key feature of understanding their biological impact, and these interactions can perhaps be exploited to mitigate unwanted toxic effects. In this Perspective we discuss recent results that address the toxicity of gold nanoparticles both in vitro and in vivo, and we provide some experimental recommendations for future research at the interface of nanotechnology and biological systems

Molecular engineering of gold nanorod surfaces: towards improved physical properties and understanding nanoparticle-cell interactions

Gold nanorods have unique optical properties and various promising applications. Wet chemical synthesis of gold nanorods requires the use of cetyl trimethylammonium bromide (CTAB) as shape-directing surfactant, which form a bilayer on the surfaces of gold nanorods. CTAB bilayer stabilizes the nanorods against aggregation and has the ability to sequester organic molecules from aqueous bulk. CTAB molecules in the bilayer are held via weak hydrophobic forces and thus tend to desorb resulting in nanorods aggregation and toxicity to cultured cells. Herein, three surface-engineering approaches to enhance the colloidal physical stability and biocompatibility of gold nanorods have been examined: 1) electrostatic approach via overcoating with polyelectrolytes; 2) covalent approach via surfactant polymerization; 3) and hydrophobic approach via cholesterol insertion into the bilayer. Layer-by-layer coating has been used to overcoat CTAB-capped nanorods with both negatively and positively charged polyelectrolytes. Compared to CTAB-capped nanorods, polyelectrolyte-coated gold nanorods showed improved stability against aggregation in culture medium and enhanced biocompatibility to cultured cells. The toxicity of CTAB-capped gold nanorod solutions was assigned quantitatively to free CTAB molecules, where gold nanorods themselves were found not toxic. Similar biocompatibility profiles for both cationic and anionic coated-gold nanorods were observed due to spontaneous protein adsorption. In growth media, all examined nanorods were covered with protein corona and thus bear similar negative effective surface charge explaining their similar toxicity profiles. ! """! ! Our covalent approach to stabilize the surfactant bilayer on the surface of gold nanorods relies on synthesizing a polymerizable version of the CTAB, which we have used to prepare gold nanoparticles (both spheres and rods). Surfactant polymerization on the surface of gold nanoparticles was found to retard surfactant desorption and thus enhance both stability against aggregation and biocombatibility of these nanomaterials. The hydrophobic approach to stabilize the CTAB bilayer on gold nanorods relies on using a bilayer-condensing agent such as cholesterol to increase the total hydrophobic interactions. Cholesterol is known to consist of up to 50% of mammalian cell membrane???s total lipids, and thus have important effect on their stability and physical properties. Using cholesterol-rich growth medium, we have prepared gold nanorods with excellent size and shape distribution. The prepared gold nanorods in the presence of cholesterol have a significantly higher surface charge and exhibit superior stability against aggregation compared to the nanorods prepared without cholesterol. In addition to the enhanced aqueous stability and biocompatibility, stabilization the CTAB bilayer on the surface of gold nanorods have allowed for suspension gold nanorods in organic solvents without aggregation. Polyelectrolyte-coated gold nanorods showed remarkable stability in polar organic solvents against aggregation as compared to CTAB-capped nanorods. The suspendability of coated-gold nanorods in polar organic solvents facilitates the incorporation of these nanomaterials into hydrophobic polymers and thus fabrication of thin films that contain uniform gold nanorod dispersions (nanocomposites)

Eutectics in Pharmacy Curriculum: A Simple Demonstration with Pharmaceutical Relevance

In chemistry, a eutectic mixture refers to a mixture of two or more components at which the lowest possible freezing point is observed. This phenomenon is covered in a wide range of curricula such as physics, chemistry, chemical engineering, and pharmacy to various depths. Despite the significance of this phenomenon in pharmaceutical compounding and formulation, standard pharmacy curricula provide only limited coverage of the eutectic mixture and the theoretical aspects associated with its phase diagram. A practical session on a eutectic mixture should augment the theoretical pedagogical component and enable a more profound understanding. Despite the existence of educational publications that discuss this phenomenon from a chemical perspective, there is currently no reported experimental laboratory specifically focused on the eutectic phenomenon and its implications in the field of pharmacy. In this study, we employ camphor and menthol as pharmaceutical active ingredients that illustrate a robust eutectic phenomenon within practical temperature ranges. Moreover, we utilize the eutectic phenomenon and the resulting liquefaction effect upon mixing camphor and menthol to prepare semisolid pharmaceutical dosage forms (gels and rubs), demonstrating to students the impact of this phenomenon in drug compounding and formulation

Synthesis of Monodispersed Gold Nanoparticles with Exceptional Colloidal Stability with Grafted Polyethylene Glycol-g-polyvinyl Alcohol

Herein, we report the synthesis of spherical gold nanoparticles with tunable core size (23–79 nm) in the presence of polyethylene glycol-g-polyvinyl alcohol (PEG-g-PVA) grafted copolymer as a reducing, capping, and stabilizing agent in a one-step protocol. The resulted PEG-g-PVA-capped gold nanoparticles are monodispersed with an exceptional colloidal stability against salt addition, repeated centrifugation, and extensive dialysis. The effect of various synthesis parameters and the kinetic/mechanism of the nanoparticle formation are discussed

Synergistic antibacterial activity of silver nanoparticles and hydrogen peroxide.

The increasing challenge of antibiotic resistance requires not only the discovery of new antibiotics, but also the development of new alternative approaches. Herein, the synergistic antibacterial activity of silver nanoparticles and hydrogen peroxide combination is reported. Unlike the bacteriostatic or slightly bactericidal activity achieved by using each agent alone, using these two agents in combination, even at relatively low concentrations, resulted in complete eradication of both the Gram negative Escherichia coli and the Gram positive Staphylococcus aureus in short treatment times indicating a clear synergistic effect between them. Modifying the surface chemistry of silver nanoparticles and the accompanied change in their surface charge enabled a further enhancement of such synergistic effect implying the importance of this aspect. Mechanistically, a Fenton-like reaction between silver nanoparticles and hydrogen peroxide is discussed and hypothesized to be the basis of the observed synergy. Achieving such a significant antibacterial activity at low concentrations reduces the potential toxicity of these agents and hence enables their utilization as an alternative antibacterial approach in wider range of applications

The Golden Liposomes: Preparation and Biomedical Applications of Gold-Liposome Nanocomposites

Gold nanoparticles (AuNP) have received a growing attention due to their fascinating physiochemical properties and promising range of biomedical applications including sensing, diagnosis and cancer photothermal ablation. AuNP enjoy brilliant optical properties and ability to convert light into local heat and function as a “nanoheaters” to fight cancer. However, AuNP are poor drug delivery systems as they do not have reservoirs or matrices to achieve an acceptable drug loading efficiency. On the other end, liposome-based nanocarriers do not exhibit such optical properties but are excellent platform for drug loading and they have been proven clinically with a true presence in the market since the FDA approved Doxil® in 1995. Combining the brilliant optical and photothermal properties of AuNP with the excellent drug loading capability of liposome should yield nanocomposites that enjoy the features of both modalities and enable the development of novel and smart drug delivery systems. Therefore, this review discusses the up-to date research on the AuNP-liposome nanocomposites and the current available approaches and protocols for their preparation and characterization. Finally, the biomedical applications of AuNP-liposome nanocomposites and proposed future directions in this field are discussed